ORCID Profile
0000-0002-8875-4135
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Medical Devices | Electrical and Electronic Engineering | Signal Processing | Applied Mathematics | Synthesis Of Macromolecules | Macromolecular and Materials Chemistry | Synthesis of Materials | Biomedical Engineering | Biomaterials | Artificial Intelligence and Image Processing | Polymers | Pattern Recognition and Data Mining | Nanomanufacturing | Signal Processing | Biological Mathematics | Functional Materials | Neurology And Neuromuscular Diseases | Neurology and Neuromuscular Diseases | Central Nervous System |
ANZSRC Socio-Economic Objective (SEO)
Nervous System and Disorders | Nervous system and disorders | Health and Support Services not elsewhere classified | Expanding Knowledge in Technology | Clinical health not specific to particular organs, diseases and conditions | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Information and Computing Sciences | Expanding Knowledge in the Biological Sciences
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Publications
Imaging in epilepsy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1994
DOI: 10.1097/00019052-199404000-00008
Abstract: Neuroimaging in epilepsy now includes magnetic resonance imaging, positron emission tomography (PET), single-photon emission tomography (SPECT), magnetoencephalography, and magnetic resonance spectroscopy. Recent advances in neuroimaging include improved rates of detection of lesions on structural imaging using quantitative methods, identification of metabolic patterns on functional imaging with PET, and recognition of the value of ictal SPECT in seizure localization.
Equality of the psychological model underlying depressive symptoms in patients with temporal lobe epilepsy versus heterogeneous neurological disorders
Publisher: Informa UK Limited
Date: 10-2006
DOI: 10.1080/13803390500376808
Abstract: Controversy surrounds the question of whether there is a specific pattern of psychopathology or personality style observed in patients with temporal lobe epilepsy (TLE) or whether the symptoms of psychological distress reflect a common disorder such as depression. Measurement equivalence was examined to test the hypothesis that the latent variable model underlying scores on the Beck Depression Inventory (BDI) was equivalent across s les of patients with TLE (n = 187) and patients with heterogeneous neurological disorders (n = 150). A well-replicated model of depression or psychological distress comprising three related variables, negative attitude, performance difficulty, and somatic elements, displayed a pattern of strict metric invariance. This result suggests that the same set of latent variables is measured with the same metric relationship between item scores and latent variables in patients with TLE and in patients with heterogeneous neurological disorders.
Epileptiform K-Complexes and Sleep Spindles: An Underreported Phenomenon in Genetic Generalized Epilepsy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2016
The use of computer-assisted-telephone-interviewing to diagnose seizures, epilepsy and Idiopathic Generalized Epilepsy
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.EPLEPSYRES.2010.06.003
Abstract: Computer-assisted-telephone-interviewing (CATI), widely used in market research, could be a useful alternative for conducting diagnostic interviews in epilepsy epidemiology. We administered a diagnostic seizure questionnaire by CATI, interpreting the responses with standardized classification guidelines, compared against an epilepsy specialist's assessment, for agreement [Kappa statistic (kappa)], sensitivity, specificity, positive predictive value, negative predictive value and Youden's Index (YI). 99 outpatients with 382 lifetime events participated: 22 generalized-onset epilepsy [16 Idiopathic Generalized Epilepsy (IGE)], 59 partial-onset epilepsy, 12 non-epileptic and 6 uncertain. We observed almost perfect agreement in diagnosing epilepsy (kappa=0.94), seizure-onset types (kappa=0.84), simple or complex partial seizures (kappa=0.87), any generalized non-convulsive seizure (kappa=0.82), and IGE (kappa=0.82). Although substantial, agreement was not as close for secondarily generalized seizures (kappa=0.74), and generalized tonic-clonic seizures (kappa=0.79). This related more to under-recognition of in idual generalized non-convulsive seizures rather than misinterpretation of partial seizures. Epilepsy diagnostic questionnaires administered by CATI and interpreted with standardized diagnostic guidelines can effectively classify epilepsy, most seizure types and IGE in outpatients with suspected seizures. Applying this diagnostic method in 'field' settings will allow firmer conclusions to be drawn on its wider epidemiological utility.
A bifurcation analysis of a modified neural field model: conductance-based synapses act as an anti-epileptic regulatory mechanism
Publisher: Springer Science and Business Media LLC
Date: 18-07-2011
Early hippocampal oxidative stress is a direct consequence of seizures in the rapid electrical amygdala kindling model
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.EPLEPSYRES.2010.06.005
Abstract: Epilepsy is characterised by recurrent seizures, which are manifestations of aberrant cortical neuronal firing. It is unclear whether oxidative stress is a cause or consequence of seizure-related hippoc al neuronal loss or whether it occurs concomitantly with the initiation of cell death pathways. We utilised the rapid electrical amygdala kindling (REAK) model which does not induce cell death to examine early seizure-induced oxidative stress in wildtype and superoxide dismutase 2 (Sod2) +/- mice, which lack 50% of Sod2 activity and are therefore known to be more susceptible to mitochondrial oxidative stress. A significant increase in lipid peroxidation and superoxide production was noted in the hippoc i of wildtype mice and a more delayed response observed in Sod2 +/- mice at early time-points post-seizures, but protein carbonylation levels appeared unchanged. A 10-fold increase in superoxide production was seen in the Sod2 +/- CA2 neurons, indicating that Sod2 plays an important role in protecting the CA2 region of the hippoc us from seizure-induced free radical damage. Early hippoc al cell death was undetectable in wildtype or Sod2 +/- mice post-seizures. We were able to demonstrate that hippoc al oxidative stress occurred as a direct consequence of seizures rather than downstream of activation of cell death pathways. We were also able to show that this increase in oxidative stress was not sufficient to cause cell death within the time window investigated. Our data indicates that a possible upregulation of endogenous antioxidant activity might exist within selective hippoc al sectors in the Sod2 +/- mice that are as yet unknown.
Clinical utility of distributed source modelling of interictal scalp EEG in focal epilepsy
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.CLINPH.2010.04.002
Abstract: Assess the clinical utility of non-invasive distributed EEG source modelling in focal epilepsy. Interictal epileptiform discharges were recorded from eight patients - benign focal epilepsy of childhood (BFEC), four mesial temporal lobe epilepsy (MTLE), four. EEG source localization (ESL) applied 48 forward-inverse-subspace set-ups: forward - standardized, leadfield-interpolated boundary element methods (BEMs, BEMi), finite element method (FEMi) inverse - minimum norm (MNLS), L1 norm (L1), low resolution electromagnetic tomography (LORETA), standardized LORETA (sLORETA) subspace- whole volume (3D), cortex with rotating sources (CxR), cortex with fixed sources (CxN), cortex with fixed extended sources (patch). Current density reconstruction (CDR) maxima defined 'best-fit'. From 19,200 CDR parameter results and 2304 CDR maps, the dominant variables on best-fit were inverse model and subspace constraint. The most clinically meaningful and statistically robust results came with sLORETA-CxR atch (lower Rolandic in BFEC, basal temporal lobe in MTLE). Computation time was inverse model dependent: sub-second (MNLS, sLORETA), seconds (L1), minutes (LORETA). From the largest number of distributed ESL approaches compared in a clinical setting, an optimum modelling set-up for BFEC and MTLE incorporated sLORETA (inverse), CxR or patch (subspace), and either BEM or FEMi (forward). Computation is efficient and CDR results are reproducible. Distributed source modelling demonstrates clinical utility for the routine work-up of unilateral BFEC of the typical Rolandic variety, and unilateral MTLE secondary to hippoc al sclerosis.
211. In hindsight – deja view....a case of palinopsia masquerading as dyslexia
Publisher: Elsevier BV
Date: 03-2009
Dipole Versus Distributed EEG Source Localization for Single Versus Averaged Spikes in Focal Epilepsy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2010
Psychosocial and neuropsychological outcomes in two high-functioning males 20 years after traumatic brain injury
Publisher: Informa UK Limited
Date: 08-1999
Hippocampal damage and duration of temporal-lobe epilepsy
Publisher: Elsevier BV
Date: 07-1998
Embodiment and Estrangement: Results from a First-in-Human “Intelligent BCI” Trial
Publisher: Springer Science and Business Media LLC
Date: 11-11-2019
The neurodynamics of epilepsy: a homotopy analysis between current-based and conductance-based synapses in a neural field model of epilepsy.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Cathodal transcranial direct-current stimulation for treatment of drug-resistant temporal lobe epilepsy: A pilot randomized controlled trial.
Publisher: Wiley
Date: 17-10-2016
DOI: 10.1002/EPI4.12020
Clinical experience with using lacosamide for the treatment of epilepsy in a tertiary centre
Publisher: Hindawi Limited
Date: 31-07-2013
DOI: 10.1111/J.1600-0404.2012.01704.X
Abstract: Lacosamide is approved for the adjunctive treatment of partial-onset seizures in adults. Phase II/III clinical trials suggest that it is a safe, effective and well-tolerated medication. However, there is little post-marketing information available about this medication. We report our clinical experience from a tertiary referral epilepsy centre, which has been using lacosamide for the past 18 months, with 128 patients treated during this time. Fifty-three patients (41%) achieved at least a 50% reduction in seizure frequency, with 14 patients (11%) achieving seizure freedom for a mean time of 35 weeks. This 50% responder rate matches, and the seizure free rate outperforms that seen in previous pooled trials. The efficacy of lacosamide did not vary with concurrent sodium channel blocking agent (SCB) use, and a statistically significant dose-dependent response was not shown, which is in contrast to previous trials. Treatment emergent adverse effects (TEAEs) were noted in 52 patients (41%), with 24 patients (19%) discontinuing the medication. TEAEs were more frequent in patients on concurrent SCBs, affecting 51% vs. 28% of patients not on other SCBs. This increased risk of TEAEs from concurrent SCB use was of statistical significance (P = 0.01). The most frequently noted TEAEs from lacosamide were dizziness, sedation and diplopia, which all appeared to be dose-related. This post-marketing analysis suggests that lacosamide in clinical practice at least mirrors, and possibly outperforms the results seen in previous phase II/III trials.
Pregnancy treatment guidelines: Throwing the baby out with the bath water
Publisher: Wiley
Date: 21-08-2009
Association of the MELAS m.3243A>G mutation with myositis and the superiority of urine over muscle, blood and hair for mutation detection.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.JOCN.2008.11.012
Abstract: A patient with a known family history of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) due to the MT-TL1 m.3243A>G mutation presented with mild myalgia and very minor upper limb proximal muscle weakness. Muscle histology revealed low levels of cytochrome oxidase-negative fibres and non-specific myositis. Using the last "hot cycle" polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), the MELAS MT-TL1 m.3243A>G mutation was only detected in urine, and not in hair, blood or skeletal muscle. This report highlights the need to screen various tissues to achieve an accurate mitochondrial genetic diagnosis and suggests the likelihood of myositis arising secondary to the MELAS MT-TL1 m.3243A>G mutation.
Efficacy and tolerability of adjuvant lacosamide
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.YEBEH.2017.11.027
Abstract: The objective of this study was to analyze the effectiveness and long-term tolerability of adjuvant lacosamide (LCM) in a multicenter cohort. We aim to assess outcomes of LCM-containing antiepileptic drug (AED) combinations based upon 'mechanism of action' (MoA) and patient's clinical features. Consecutive patients commenced on LCM, with focal epilepsy were identified from three Australian hospitals. The 12-month efficacy endpoints were greater than 50% reduction in seizure frequency (responders) and seizure freedom. Tolerability endpoints were cessation of LCM for any reason, cessation due to side-effects and censoring due to inefficacy. Outcomes were assessed according to concomitant AEDs according to their MoA and the clinical risk factor profile. Three hundred ten patients were analyzed and followed for median 17.3months. Two hundred ninety-nine (97%) had drug-resistant epilepsy, and 155 (50%) had tried more than 7 AEDs at LCM commencement. Adjuvant LCM was associated with responder and seizure freedom rate of 29% and 9% respectively at 12months. Lower baseline seizure frequency, a prior 6-month period of seizure freedom at any time since epilepsy diagnosis and being on fewer concomitant AEDs were predictive of 12-month seizure freedom. Previous focal to bilateral tonic-clonic seizures (FBTCS), lower baseline seizure frequency, and concomitant AED reduction after LCM commencement were associated with improved LCM tolerability. No specific MoA AED combinations offered any efficacy or tolerability advantage. Adjuvant LCM is associated with seizure freedom rates of 9% at 12months after commencement and is predicted by lower prior seizure frequency, a period of 6months or longer of seizure freedom since diagnosis and fewer concomitant AEDs. While the broad MoA of concomitant AEDs did not influence efficacy or tolerability outcomes, we have provided a framework that may be utilized in future studies to help identify optimal synergistic AED combinations.
612: Long-term assessment of oxcarbazepine in a naturalistic setting: a retrospective study
Publisher: Elsevier BV
Date: 10-2007
Preoperative evaluation for temporal lobe surgery
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0967-5868(03)00080-8
Abstract: Temporal lobe epilepsy (TLE), the most common form of partial epilepsy in adults is often refractory to medical treatment and in these patients epilepsy surgery is considered. Successful surgery is dependent on accurate localisation and lateralisation of the epileptogenic zone. The preoperative evaluation involves a series of assessments and investigations including detailed clinical history, interictal EEG, video-EEG monitoring, MRI, PET, SPECT, and neuropsychology and neuropsychiatric assessment. The role of each of these investigations and assessments in the preoperative evaluation is discussed. Advanced MR techniques including magnetic resonance spectroscopy, MR diffusion and MR perfusion have recently been assessed and are likely to enhance the pre-surgical evaluation of patients with TLE.The surgical outcome and preoperative investigations performed of 80 consecutive patients who underwent temporal lobe surgery between 1993 and 2002 at Royal Melbourne Hospital were reviewed. All patients had MRI, video-EEG monitoring and neuropsychology assessment and 56% a PET scan. During a mean follow-up of 5.9 years 75% had Class 1 outcome, 22% non-Class 1 outcome and 3% were lost to follow-up. The results of preoperative investigations were correlated with outcome. For interictal EEG, seizure semiology, ictal EEG, PET and neuropsychology assessment the surgical outcome of patients in whom results were concordant to side of surgery was compared with those discordant or non-lateralising. There was no significant difference. In 78 of 80 patients MRI revealed mesial temporal sclerosis or a foreign tissue lesion. The outcome was no different between these two groups. Results suggest that in patients with unilateral temporal lobe lesion on MRI and where ictal EEG is either concordant or non-lateralising, other investigations including PET, provide little additional prognostic information.
“Magnetic Resonance Imaging Negative Positron Emission Tomography Positive” Temporal Lobe Epilepsy: FDG-PET Pattern Differs from Mesial Temporal Lobe Epilepsy
Publisher: Springer Science and Business Media LLC
Date: 19-12-2006
DOI: 10.1007/S11307-006-0073-0
Abstract: Some patients with temporal lobe epilepsy (TLE) lack evidence of hippoc al sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would have a different pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with evidence of hippoc al atrophy on magnetic resonance imaging (MRI) (HS+ve), with a lateral temporal neocortical rather than mesial focus. Thirty consecutive HS-ve patients and 30 age- and sex-matched HS+ve patients with well-lateralized EEG were identified. FDG-PET was performed on 28 HS-ve patients and 24 HS+ve patients. Both groups were compared using statistical parametric mapping (SPM), directly and with FDG-PET from 20 healthy controls. Both groups showed lateralized temporal hypometabolism compared to controls. In HS+ve, this was antero-infero-mesial (T = 17.13) in HS-ve the main clustering was inferolateral (T = 17.63). When directly compared, HS+ve had greater hypometabolism inmesial temporal/hippoc al regions (T = 4.86) HS-ve had greater inferolateral temporal hypometabolism (T = 4.18). These data support the hypothesis that focal hypometabolism involves primarily lateal neocortical rather than mesial temporal structures in 'MRI-negative PET-positive TLE.'
GUILLAIN‐BARRÉ SYNDROME AND RELATED CONDITIONS IN VICTORIAN TEACHING HOSPITALS 1980–84
Publisher: Wiley
Date: 12-1989
DOI: 10.1111/J.1445-5994.1989.TB00335.X
Abstract: Cases of Guillain-Barré syndrome, its variants, and chronic inflammatory demyelinating neuropathy presenting during the period 1980-84 were identified through computer-based record systems. Case notes were examined, and cases that did not meet standard criteria for diagnosis were excluded. A hundred and ten patients were identified, giving an annual adult incidence rate of 0.9/100,000 and a male:female ratio of 1.3:1. The majority of cases developed severe tetraparesis, but unusual presentations included the Miller-Fisher variant, paraplegia, and bibrachial involvement. There was wide variation in peak disability, ranging from ambulant with weakness (32%), through bedfast but without significant respiratory involvement (29%), to respiratory involvement requiring admission to an intensive care unit (38%). Of those discharged directly home, the average hospital stay for those less than 50 years was 27 days, whilst that for those over 50 was 49 days. CSF protein was measured in 87 patients, and was greater than or equal to 0.6 g/L in 76% of these. Nerve conduction studies were performed in 52 patients, and were abnormal in 90% of these. Guillain-Barré syndrome and allied conditions represent a major drain on health resources, and the need to provide adequate plasmapheresis facilities for patients early in the course of severe disease is stressed.
Differential Diagnosis of Epilepsy
Publisher: Wiley
Date: 22-07-2009
The influence of gender on the aggravation of absence seizures by carbamazepine in the low-dose pentylenetetrazol rat model
Publisher: Elsevier BV
Date: 06-2004
Perfusion patterns in postictal Tc-99m-HMPAO SPECT after coregistration with MRI in patients with mesial temporal lobe epilepsy
Publisher: BMJ
Date: 08-1997
Abstract: To assess patterns of postictal cerebral blood flow in the mesial temporal lobe by coregistration of postictal 99mTc-HMPAO SPECT with MRI in patients with confirmed mesial temporal lobe epilepsy. Ten postictal and interictal 99mTc-HMPAO SPECT scans were coregistered with MRI in 10 patients with confirmed mesial temporal lobe epilepsy. Volumetric tracings of the hippoc us and amygdala from the MRI were superimposed on the postictal and interictal SPECT. Asymmetries in hippoc al and amygdala SPECT signal were then calculated using the equation: % Asymmetry =100 x (right - left) / (right + left)/2. In the postictal studies, quantitative measurements of amygdala SPECT intensities were greatest on the side of seizure onset in all cases, with an average % asymmetry of 11.1, range 5.2-21.9. Hippoc al intensities were greatest on the side of seizure onset in six studies, with an average % asymmetry of 9.6, range 4.7-12.0. In four scans the hippoc al intensities were less on the side of seizure onset, with an average % asymmetry of 10.2, range 5.7-15.5. There was no localising quantitative pattern in interictal studies. Postictal SPECT shows distinctive perfusion patterns when coregistered with MRI, which assist in lateralisation of temporal lobe seizures. Hyperperfusion in the region of the amygdala is more consistently lateralising than hyperperfusion in the region of the hippoc us in postictal studies.
Hippocampal atrophy is not a major determinant of regional hypometabolism in temporal lobe epilepsy
Publisher: Wiley
Date: 1997
DOI: 10.1111/J.1528-1157.1997.TB01080.X
Abstract: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) temporal lobe hypometabolism in patients with hippoc al sclerosis (HS) is uncertain. We tested the hypothesis that hippoc al atrophy, which is strongly correlated with hippoc al cell loss, is largely responsible for the regional hypometabolism in HS. Regions of interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry index for each ROI was calculated. These results were correlated with hippoc al magnetic resonance imaging (MRI) volume ratios. There was no correlation between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio for the mesial or lateral temporal regions (r = -0.09, r = -0.04). When the right/left asymmetry index was compared with the right/left hippoc al volume ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply indicated that both tests accurately reflect the side of the epileptogenic region. The concordance of the side of relative hypometabolism of the FDG-PET with the side of the hippoc al atrophy was higher for the mesial temporal region (100%) than for the lateral (77.5%). The lack of correlation between the magnitudes of the ratios argues against hippoc al atrophy and cell loss having a central role in the FDG-PET temporal hypometabolism.
Cycles in epilepsy
Publisher: Springer Science and Business Media LLC
Date: 15-03-2021
DOI: 10.1038/S41582-021-00464-1
Abstract: Epilepsy is among the most dynamic disorders in neurology. A canonical view holds that seizures, the characteristic sign of epilepsy, occur at random, but, for centuries, humans have looked for patterns of temporal organization in seizure occurrence. Observations that seizures are cyclical date back to antiquity, but recent technological advances have, for the first time, enabled cycles of seizure occurrence to be quantitatively characterized with direct brain recordings. Chronic recordings of brain activity in humans and in animals have yielded converging evidence for the existence of cycles of epileptic brain activity that operate over erse timescales: daily (circadian), multi-day (multidien) and yearly (circannual). Here, we review this evidence, synthesizing data from historical observational studies, modern implanted devices, electronic seizure diaries and laboratory-based animal neurophysiology. We discuss advances in our understanding of the mechanistic underpinnings of these cycles and highlight the knowledge gaps that remain. The potential clinical applications of a knowledge of cycles in epilepsy, including seizure forecasting and chronotherapy, are discussed in the context of the emerging concept of seizure risk. In essence, this Review addresses the broad question of why seizures occur when they occur.
DNA electroporation in vivo targets mature fibres in dystrophic mdx muscle
Publisher: Elsevier BV
Date: 10-2005
DOI: 10.1016/J.NMD.2005.04.008
Abstract: Non-viral gene transfer into skeletal muscle is enhanced by electroporation and myotoxin preconditioning of muscle following plasmid injection. We investigated in vivo delivery of naked DNA to mdx mouse muscle, utilising enhanced green fluorescent protein reporter vector (pEGFP) and a corrective nucleic acid to promote targeted corrective gene conversion at the mutant mdx mouse dystrophin (DMDmdx) locus. Electroporation, myoablation with bupivacaine and a combined protocol, were applied to mdx muscle. We report up to 90% EGFP expression in electroporated mdx tibialis anterior muscle. Muscles preconditioned with bupivacaine showed low transgene expression with or without EP. Single EGFP+ve muscle fibre explants showed EGFP expression in mature fibres in preference to satellite cells. We observed a two-fold increase (P<0.005 t) in dystrophin protein, accompanied by wild-type (wt) DMD transcript in muscles injected with corrective nucleic acid over contralateral saline-injected TAs. By targeting the muscle fibres in preference to the satellite cells, plasmid-bourne transgenes delivered to dystrophic muscle will not penetrate the regenerative component of muscle. Whether in the context of targeted corrective gene conversion or therapeutic non-viral transgenes, under these conditions periodic re-administration will be required to promote phenotypic benefits in dystrophic muscle.
The electroencephalogram of idiopathic generalized epilepsy
Publisher: Wiley
Date: 09-12-2011
DOI: 10.1111/J.1528-1167.2011.03344.X
Abstract: Idiopathic generalized epilepsy (IGE) is classified into several subsyndromes based on clinical and electroencephalography (EEG) features. The EEG signature of IGE is bisynchronous, symmetric, and generalized spike-wave complex although focal, irregular, and so called "fragments" of discharges are not uncommon. Other characteristic EEG features include polyspikes, polyspike-wave discharges, occipital intermittent rhythmic delta activity, and photoparoxysmal response. Both human and animal data suggest involvement of the thalamus and the cortex in the generation of spike-wave discharges in IGE. Circadian variations of generalized epileptiform discharges are well described, and these can be useful in diagnostic confirmation. Those discharges tend to occur more often after awakening and during cyclic alternating pattern phase-A of non-rapid eye movement sleep. Activation procedures such as hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are useful techniques to increase the yield of both interictal and ictal EEG abnormalities. Although not in routine use, specific triggers such as pattern stimulation and cognitive tasks may also be of value in eliciting rare reflex seizure-related EEG abnormalities. Variations of EEG abnormalities are evident between different electroclinical syndromes. EEG is also affected by certain external as well as internal factors, which should be borne in mind when interpreting EEG studies in IGE.
The prognosis of idiopathic generalized epilepsy
Publisher: Wiley
Date: 25-10-2012
DOI: 10.1111/J.1528-1167.2012.03723.X
Abstract: Prognosis describes the trajectory and long-term outcome of a condition. Most studies indicate a better prognosis in idiopathic generalized epilepsy (IGE) in comparison with other epilepsy syndromes. Studies looking at the long-term outcome of different IGE syndromes are relatively scant. Childhood absence epilepsy appears to have a higher rate of remission compared to juvenile absence epilepsy. In absence epilepsies, development of myoclonus and generalized tonic-clonic seizures predicts lower likelihood of remission. Although most patients with juvenile myoclonic epilepsy (JME) achieve remission on antiepileptic drug therapy, <20% appear to remain in remission without treatment. Data on the prognosis of other IGE syndromes are scarce. There are contradictory findings reported on the value of electroencephalography as a predictor of prognosis. Comparisons are made difficult by study heterogeneity, particularly in methodology and diagnostic criteria.
Simulating clinical trials with and without intracranial EEG data
Publisher: Wiley
Date: 18-01-2017
DOI: 10.1002/EPI4.12038
Closed-loop seizure control with very high frequency electrical stimulation at seizure onset in the GAERS model of absence epilepsy.
Publisher: World Scientific Pub Co Pte Lt
Date: 04-2011
DOI: 10.1142/S0129065711002717
Abstract: A closed-loop system for the automated detection and control of epileptic seizures was created and tested in three Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats. In this preliminary study, a set of four EEG features were used to detect seizures and three different electrical stimulation strategies (standard (130 Hz), very high (500 Hz) and ultra high (1000 Hz)) were delivered to terminate seizures. Seizure durations were significantly shorter with all three stimulation strategies when compared to non-stimulated (control) seizures. We used mean seizure duration of epileptiform discharges persisting beyond the end of electrical stimulation as a measure of stimulus efficacy. When compared to the duration of seizures stimulated in the standard approach (7.0 s ± 10.1), both very high and ultra high frequency stimulation strategies were more effective at shortening seizure durations (1.3 ± 2.2 s and 3.5 ± 6.4 s respectively). Further studies are warranted to further understand the mechanisms by which this therapeutic effect may be conveyed, and which of the novel aspects of the very high and ultra high frequency stimulation strategies may have contributed to the improvement in seizure abatement performance when compared to standard electrical stimulation approaches.
Introduction
Publisher: World Scientific Pub Co Pte Lt
Date: 08-11-2016
Can EEG differentiate among syndromes in genetic generalized epilepsy?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2017
DOI: 10.1097/WNP.0000000000000358
Abstract: To evaluate EEG differences among syndromes in genetic generalized epilepsy based on quantified data. Twenty-four-hour ambulatory EEGs were recorded in consecutive patients diagnosed with genetic generalized epilepsy. All epileptiform EEG abnormalities were quantified into density scores (total duration of epileptiform discharges per hour). One-way analysis of variance was conducted to find out differences in EEG density scores among the syndromes. Generalized linear mixed models were also fitted to explore the association between the proportion of “pure” generalized spike–wave paroxysms and fragments (without intervening polyspikes olyspike–waves) and the syndromes. In total, 6,923 epileptiform discharges were analyzed from 105 abnormal EEGs. In the analysis of variance, six EEG variables were significantly different among syndromes: total spike density ( P = 0.001), total polyspike and polyspike–wave density ( P = 0.049), generalized spike–wave–only density ( P 0.001), generalized paroxysm density ( P 0.001), generalized paroxysm duration mean ( P = 0.018), and generalized paroxysm duration maximum ( P = 0.009). The density of epileptiform discharges and the paroxysm durations were the highest in juvenile absence epilepsy followed by juvenile myoclonic epilepsy, childhood absence epilepsy, and generalized epilepsy with tonic–clonic seizures only. Generalized linear mixed models revealed that “pure” generalized spike–wave discharges (without intervening polyspikes olyspike waves) tended to be more frequent in absence epilepsies, although the difference was not statistically significant ( P = 0.21). The findings of this study suggest that the density and duration of epileptiform discharges can help differentiate among genetic generalized epilepsy syndromes.
Capturing the epileptic trait: cortical excitability measures in patients and their unaffected siblings
Publisher: Oxford University Press (OUP)
Date: 12-03-2013
DOI: 10.1093/BRAIN/AWT047
Abstract: We used transcranial magnetic stimulation to investigate whether the cortical excitability changes observed amongst the different generalized and focal epilepsy syndromes are reflected in their asymptomatic siblings and if these changes depended on the clinical phenotype. We studied 157 patients with epilepsy (95 generalized and 62 focal) and their asymptomatic siblings (138 and 82, respectively). Motor threshold and paired pulse transcranial magnetic stimulation at short (2, 5, 10 and 15 ms) and long (100-300 ms) interstimulus intervals were measured. Results were compared to those of 12 control subjects and 20 of their siblings. There were no differences in cortical excitability between healthy control subjects and their siblings. Compared with control subjects, cortical excitability was higher in siblings of patients whether generalized (P < 0.05 short and long interstimulus intervals) or focal (P < 0.05 long interstimulus intervals). Compared with epilepsy, motor threshold was lower (P < 0.05) in patients with juvenile myoclonic epilepsy compared with their siblings only early at onset in the drug naïve state. In all groups (generalized and focal) cortical excitability was lower in siblings only at the long interstimulus intervals (250 and 300 P < 0.05). Cortical excitability is higher in asymptomatic siblings of patients with generalized and focal epilepsy in a similar manner. The disturbance seems to involve intracortical inhibitory circuits even in the siblings of patients with a structural abnormality (acquired epilepsy). This implies there are certain genetic factors that predispose to both generalized and focal epilepsies and a complex genetic/environmental interaction then determines the clinical phenotype.
High-Frequency Oscillations in Epilepsy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-03-2021
DOI: 10.1212/WNL.0000000000011465
Abstract: For the past 2 decades, high-frequency oscillations (HFOs) have been enthusiastically studied by the epilepsy community. Emerging evidence shows that HFOs harbor great promise to delineate epileptogenic brain areas and possibly predict the likelihood of seizures. Investigations into HFOs in clinical epilepsy have advanced from small retrospective studies relying on visual identification and correlation analysis to larger prospective assessments using automatic detection and prediction strategies. Although most studies have yielded promising results, some have revealed significant obstacles to clinical application of HFOs, thus raising debate about the reliability and practicality of HFOs as clinical biomarkers. In this review, we give an overview of the current state of HFO research and pinpoint the conceptual and methodological issues that have h ered HFO translation. We highlight recent insights gained from long-term data, high-density recordings, and multicenter collaborations and discuss the open questions that need to be addressed in future research.
Crowdsourcing seizure detection: algorithm development and validation on human implanted device recordings
Publisher: Oxford University Press (OUP)
Date: 27-04-2017
DOI: 10.1093/BRAIN/AWX098
Molecular and morphological analyses support recognition of Prostanthera volucris (Lamiaceae), a new species from the Central Tablelands of New South Wales
Publisher: Cold Spring Harbor Laboratory
Date: 22-12-2021
DOI: 10.1101/2021.12.21.473648
Abstract: Research into the systematics of Prostanthera has recently revealed a close evolutionary relationship among P. phylicifolia s. str. , the critically endangered P. gilesii , and a population of uncertain identity from the Central Tablelands of New South Wales, Australia. Previous analyses were unable to establish whether genetic boundaries separated these taxa. This study aimed to assess the species boundaries among these three taxa using a combination of single-nucleotide polymorphisms (SNP) s led at the population-scale and multivariate analysis of morphological characters. Non-parametric and parametric statistics, neighbour-network analysis, phylogenetic analysis, and ancestry coefficient estimates all provided support for discrete genetic differences between the three taxa. Morphological phenetic analysis identified a suite of characters that distinguished each of these taxa. This corroboration of evidence supports the presence of three independently evolving lineages. Prostanthera gilesii and P. phylicifolia s. str. are distinct species independent from the third taxon which is described here as P. volucris R.P.O’Donnell. A detailed description, diagnostic line drawings and photographs are provided. We evaluate P. volucris as satisfying criteria to be considered Critically Endangered.
Common data elements for epilepsy mobile health systems
Publisher: Wiley
Date: 31-03-2018
DOI: 10.1111/EPI.14066
Postictal suppression and seizure durations: A patient-specific, long-term iEEG analysis
Publisher: Wiley
Date: 06-04-2018
DOI: 10.1111/EPI.14065
Abstract: We report on patient-specific durations of postictal periods in long-term intracranial electroencephalography (iEEG) recordings. The objective was to investigate the relationship between seizure duration and postictal suppression duration. Long-term recording iEEG from 9 patients (>50 seizures recorded) were analyzed. In total, 2310 seizures were recorded during a total of 13.8 years of recording. Postictal suppression duration was calculated as the duration after seizure termination until total signal energy returned to background levels. The relationship between seizure duration and postictal suppression duration was quantified using the correlation coefficient (r). The effects of populations of seizures within patients, on correlations, were also considered. Populations of seizures within patients were distinguished by seizure duration thresholds and k-means clustering along the dimensions of seizure duration and postictal suppression duration. The effects of bursts of seizures were also considered by defining populations based on interseizure interval (ISI). Seizure duration accounted for 40% of postictal suppression duration variance, aggregated across all patients and seizures. Seizure duration accounted for more than 25% of the variance in postictal suppression duration in 2 patients and accounted for less than 25% in the remaining 7. In 3 patients, heat maps showed multiple distinct postictal patterns indicating multiple populations of seizures. When accounting for these populations, seizure duration accounted for less than 25% of the variance in postictal duration in all populations. Variance in postictal suppression duration accounted for less than 10% of ISI variance in all patients. We have previously demonstrated that some patients have multiple seizure populations distinguishable by seizure duration. This article shows that different seizure populations have distinct and consistent postictal behaviors. The existence of multiple populations in some patients has implications for seizure management and forecasting, whereas the distinct postictal behaviors may have implications for sudden unexpected death in epilepsy (SUDEP) prediction and prevention.
Forecasting cycles of seizure likelihood
Publisher: Wiley
Date: 27-03-2020
DOI: 10.1111/EPI.16485
Neuroimaging in the investigation of epilepsy
Publisher: Oxford University Press
Date: 12-2013
Estimation of effective connectivity via data-driven neural modeling
Publisher: Frontiers Media SA
Date: 28-11-2014
Advanced fabrication approaches to controlled delivery systems for epilepsy treatment
Publisher: Informa UK Limited
Date: 02-09-2018
DOI: 10.1080/17425247.2018.1517745
Abstract: Epilepsy is a chronic brain disease characterized by unprovoked seizures, which can have severe consequences including loss of awareness and death. Currently, 30% of epileptic patients do not receive adequate seizure alleviation from oral routes of medication. Over the last decade, local drug delivery to the focal area of the brain where the seizure originates has emerged as a potential alternative and may be achieved through the fabrication of drug-loaded polymeric implants for controlled on-site delivery. This review presents an overview of the latest advanced fabrication techniques for controlled drug delivery systems for refractory epilepsy treatment. Recent advances in the different techniques are highlighted and the limitations of the respective techniques are discussed. Advances in biofabrication technologies are expected to enable a new paradigm of local drug delivery systems through offering high versatility in controlling drug release profiles, personalized customization and multi-drug incorporation. Tackling some of the current issues with advanced fabrication methods, including adhering to GMP-standards and industrial scale-up, together with innovative solutions for complex designs will see to the maturation of these techniques and result in increased clinical research into implant-based epilepsy treatment. GMP: Good manufacturing process DDS(s): Drug delivery system(s) 3D: Three-dimensional AEDs: Anti-epileptic drugs BBB: Blood brain barrier PLA: Polylactic acid PLGA: Poly(lactic-co-glycolic acid) PCL: poly(ɛ-caprolactone) ESE: Emulsification solvent evaporation O/W: Oil-in-water W/O/W: Water-in-oil-in-water DZP: Diazepam PHT: Phenytoin PHBV: Poly(hydroxybutyrate-hydroxyvalerate) PEG: Polyethylene glycol SWD: Spike-and-wave discharges CAD: Computer aided design FDM: Fused deposition modeling ABS: Acrylonitrile butadiene styren eEVA: Ethylene-vinyl acetate GelMA: Gelatin methacrylate PVA: Poly-vinyl alcohol PDMS: Polydimethylsiloxane SLA: Stereolithography SLS: Selective laser sintering.
Development and validation of an epidemiologic case definition of epilepsy for use with routinely collected Australian health data
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.YEBEH.2015.06.031
Abstract: We report the diagnostic validity of a selection algorithm for identifying epilepsy cases. Retrospective validation study of International Classification of Diseases 10th Revision Australian Modification (ICD-10AM)-coded hospital records and pharmaceutical data s led from 300 consecutive potential epilepsy-coded cases and 300 randomly chosen cases without epilepsy from 3/7/2012 to 10/7/2013. Two epilepsy specialists independently validated the diagnosis of epilepsy. A multivariable logistic regression model was fitted to identify the optimum coding algorithm for epilepsy and was internally validated. One hundred fifty-eight out of three hundred (52.6%) epilepsy-coded records and 0/300 (0%) nonepilepsy records were confirmed to have epilepsy. The kappa for interrater agreement was 0.89 (95% CI=0.81-0.97). The model utilizing epilepsy (G40), status epilepticus (G41) and ≥1 antiepileptic drug (AED) conferred the highest positive predictive value of 81.4% (95% CI=73.1-87.9) and a specificity of 99.9% (95% CI=99.9-100.0). The area under the receiver operating curve was 0.90 (95% CI=0.88-0.93). When combined with pharmaceutical data, the precision of case identification for epilepsy data linkage design was considerably improved and could provide considerable potential for efficient and reasonably accurate case ascertainment in epidemiological studies.
Clinical utility of EEG in diagnosing and monitoring epilepsy in adults
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.CLINPH.2018.01.019
Abstract: Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.
Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study
Publisher: Elsevier BV
Date: 06-2013
Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation
Publisher: Wiley
Date: 16-06-2015
DOI: 10.1002/DMRR.2652
Abstract: This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing. Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation. The long-term maintenance of hypoglycaemia awareness that returns after islet cell ancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure.
Seizure Prediction: Science Fiction or Soon to Become Reality?
Publisher: Springer Science and Business Media LLC
Date: 24-09-2015
DOI: 10.1007/S11910-015-0596-3
Abstract: This review highlights recent developments in the field of epileptic seizure prediction. We argue that seizure prediction is possible however, most previous attempts have used data with an insufficient amount of information to solve the problem. The review discusses four methods for gaining more information above standard clinical electrophysiological recordings. We first discuss developments in obtaining long-term data that enables better characterisation of signal features and trends. Then, we discuss the usage of electrical stimulation to probe neural circuits to obtain robust information regarding excitability. Following this, we present a review of developments in high-resolution micro-electrode technologies that enable neuroimaging across spatial scales. Finally, we present recent results from data-driven model-based analyses, which enable imaging of seizure generating mechanisms from clinical electrophysiological measurements. It is foreseeable that the field of seizure prediction will shift focus to a more probabilistic forecasting approach leading to improvements in the quality of life for the millions of people who suffer uncontrolled seizures. However, a missing piece of the puzzle is devices to acquire long-term high-quality data. When this void is filled, seizure prediction will become a reality.
Clinical utility of current-generation dipole modelling of scalp EEG
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.CLINPH.2007.08.016
Abstract: To investigate the clinical utility of current-generation dipole modelling of scalp EEG in focal epilepsies seen commonly in clinical practice. Scalp EEG recordings from 10 patients with focal epilepsy, five with Benign Focal Epilepsy of Childhood (BFEC) and five with Mesial Temporal Lobe Epilepsy (MTLE), were used for interictal spike dipole modelling using Scan 4.3 and CURRY 5.0. Optimum modelling parameters for EEG source localisation (ESL) were sought by the step-wise application of various volume conductor (forward) and dipole (inverse) models. Best-fit ESL solutions (highest explained forward-fit to measured data variance) were used to characterise best-fit forward and inverse models, regularisation effect, additional electrode effect, single-to-single spike and single-to-averaged spike variability, and intra- and inter-operator concordance. Inter-parameter relationships were examined. Computation times and interface problems were recorded. For both BFEC and MTLE, the best-fit forward model was the finite element method interpolated (FEMi) model, while the best-fit single dipole models were the rotating non-regularised and the moving regularised models. When combined, these forward-inverse models appeared to offer clinically meaningful ESL results when referenced to an averaged cortex overlay, best-fit dipoles localising to the central fissure region in BFEC and to the basolateral temporal region in MTLE. Single-to-single spike and single-to-averaged spike measures of concordance for dipole location and orientation were stronger for BFEC versus MTLE. The use of an additional pair of inferior temporal electrodes in MTLE directed best-fit dipoles towards the basomesial temporal region. Inverse correlations were noted between unexplained variance (RD) and dipole strength (Amp), RD and signal to noise ratio (SNR), and SNR and confidence ellipsoid (CE) volume. Intra- and inter-operator levels of agreement were relatively robust for dipole location and orientation. Technical problems were infrequent and modelling operations were performed within 5min. The optimal forward-inverse single dipole modelling set-up for BFEC and MTLE interictal spike analysis is the FEMi model using the combination of rotating non-regularised and moving regularised dipoles. Dipole modelling of single spikes characterises best-fit dipole location and orientation more reliably in BFEC than in MTLE for which spike averaging is recommended. The clinical utility of dipole modelling in two common forms of focal epilepsy strengthens the case for its place in the routine clinical work-up of patients with localisation-related epilepsy syndromes.
The Cost-Effective Use of 18F-FDG PET in the Presurgical Evaluation of Medically Refractory Focal Epilepsy
Publisher: Society of Nuclear Medicine
Date: 15-05-2008
DOI: 10.2967/JNUMED.107.048207
Abstract: This study applied decision tree analysis to evaluate the sensitivity, specificity, and cost-effectiveness of clinical algorithms that incorporate 18F-FDG PET. A cohort of 176 patients was studied. The localization rate, accuracy, therapeutic impact on the presurgical decision-making process, and correlation with the postsurgical outcome were assessed for the tests commonly performed for seizure localization. Decision tree sensitivity analysis compared 3 imaging strategies with a baseline strategy of medical therapy for all: video-electroencephalography monitoring (VEM)/MRI strategy, in which patients underwent VEM and brain MRI only, and +SPECT and +PET strategies, in which patients with an indeterminate VEM/MRI result underwent ictal SPECT or interictal 18F-FDG PET, respectively. The localization rates for VEM, MRI, 18F-FDG PET, ictal SPECT, and intracranial electroencephalography (EEG) were 62.2%, 35.8%, 75.0%, 60.0%, and 93.8%. The VEM/MRI strategy had the lowest cost per class I/II outcome, but the additional costs per class I/II outcome for the +PET and +SPECT strategies were always below the minimum reported cost savings for a class I/II outcome. There were no valid conditions in which the +SPECT strategy had a lower cost per class I/II outcome than the +PET strategy. Within the range of cost savings estimated to be associated with a class I/II outcome, all decision strategies produced net cost savings however, these were significantly higher for the +PET and the +SPECT strategies. 18F-FDG PET is cost-effective in the presurgical evaluation, particularly when used in patients with a nonlocalizing or nonconcordant VEM or MRI result.
Insertion of depth electrodes with or without subdural grids using frameless stereotactic guidance systems - Technique and outcome
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1080/02688690220131886
Abstract: Over recent years frameless stereotactic systems have begun replacing framed systems for many neurosurgical procedures. However, little has been published regarding the use of these systems to guide intracranial electrode implantation for epilepsy surgery patients. Here we report our experience utilising such a system to insert depth electrodes and subdural grid electrodes. The SteathStation Image-Guided System (SSIGS) (Sofamor Danek, Memphis TN.) was used to insert bilateral depth electrodes in 13 patients, of whom 5 also underwent the insertion of subdural grids or strip electrodes. Initially, a surgical plan based on an entry and target point on axial and sagittal images was performed for the insertion of electrodes. Navigational views, using three-planar images, were then performed to determine which structures the electrodes would pass through to be correctly placed in the amygdala and hippoc us. The correct site of electrode implantation was confirmed post-operatively by spiral CT scans in 4 patients (which were then co-registered to the pre-implantation MRI using a surface matching technique) and the other 9 patients by post-implantation MRI. The SSIGS was found to have a mean registration error of 2.0 mm (range 1.8-2.5) in 10 cases in the 3 cases where the error was greater than 2.5 mm a surfacemerge technique was used with a mean error 0.9 (0.8-1.00). The post-implantation MRI or CT-MRI co-registration confirmed an accurate electrode placement in the mesial temporal region in all cases. Seizure onset lateralisation was achieved in 11 patients, all of whom went onto formal resections based on these results. The only long-term complication was a case of osteomyelitis which required removal of the bone flap. 73% of patients had an excellent seizure outcome. Frameless stereotactic systems can be safely used to intracranial electrodes, avoid the disadvantages of the framed system and have the added advantage of the surgeon being able to visualise the trajectory and to adjust this to avoid vital structures. As well they eliminate surgical obstruction to the insertion of subdural grids at the same operation, which may be caused by a framed system.
Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.JOCN.2012.05.017
Abstract: Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site.
Focal abnormalities in idiopathic generalized epilepsy: A critical review of the literature
Publisher: Wiley
Date: 17-06-2014
DOI: 10.1111/EPI.12688
Abstract: Conventionally, epilepsy is dichotomized into distinct "focal" and "generalized" categories. However, many studies have reported so-called focal features among patients with idiopathic generalized epilepsy (IGE) in the domains of semiology, electroencephalography, neuropsychology, neuropathology, and neuroimaging. We sought to review such features and clinical implications. A Web of Science database search was conducted to identify relevant publications. Our search yielded 145 papers describing focal features involving different domains in IGE, with 117 papers analyzed after excluding abstracts and case reports. Focal semiologic features are commonly seen in IGE. There are conflicting data from studies in the domains of electroencephalography, neuroimaging, and neuropathology. Studies on neuropsychology are suggestive of frontal lobe functional deficits in juvenile myoclonic epilepsy. Most advanced neuroimaging studies demonstrate the involvement of both the thalamus and the cortex during generalized spike-wave discharges (GSWDs). A few electroencephalographic and neuroimaging studies indicate that the cortex precedes the thalamus at the onset of GSWD. Focal features may contribute to misdiagnosis of IGE as focal epilepsy. However there are methodologic limitations in the studies that affect the results.
Should older patients be denied temporal lobectomy on the basis of age?
Publisher: Informa UK Limited
Date: 12-2010
DOI: 10.1586/ERN.10.62
Curing of Oscillating Larynx by Levetiracetam
Publisher: American Medical Association (AMA)
Date: 08-2011
Visual disturbances representing occipital lobe epilepsy in patients with cerebral calcifications and coeliac disease: a case series
Publisher: BMJ
Date: 11-2004
Seizures during high-dose antidepressant therapy: A case series with clinical and video-electroencephalography characteristics
Publisher: Wiley
Date: 09-2013
DOI: 10.1111/IMJ.12239
Abstract: This case series identified drug causes of seizures in patients with depressive disorders. Three patients with seizures were admitted for video-electroencephalography (EEG) monitoring in the context of high-dose antidepressants and sodium valproate. Very high-dose antidepressants caused complex partial seizures with secondary generalisation that gave characteristic EEG discharges. This is the first reported series to capture the ictal EEG features associated with antidepressants.
Epilepsy Surgery for Pathologically Proven Hippocampal Sclerosis Provides Long-term Seizure Control and Improved Quality of Life
Publisher: Wiley
Date: 18-02-2004
DOI: 10.1111/J.0013-9580.2004.35903.X
Abstract: To examine long-term seizure and quality-of-life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippoc al sclerosis (HS). Previous research has had limited follow-up (generally or=2 years' follow-up. All patients were sent a postal survey concerning seizure activity, quality of life (QOLIE-89), and antiepileptic drug (AED) use. The mean follow-up was 5.8 years (range, 2-9.2). The rate of complete postoperative seizure freedom was 82% at 12 months, 76% at 24 months, and 64% at 63 months (no further seizure recurrences observed after this time). A class I seizure outcome was achieved by 83.3% of patients. Patients with better seizure outcome had significantly better quality of life (Kendall's tau =-234, p or=2 years after surgery. Long-term quality of life is dependent on seizure outcome.
Chronic intracranial EEG recordings and interictal spike rate reveal multiscale temporal modulations in seizure states
Publisher: Oxford University Press (OUP)
Date: 2023
DOI: 10.1093/BRAINCOMMS/FCAD205
Abstract: Many biological processes are modulated by rhythms on circadian and multidien timescales. In focal epilepsy, various seizure features, such as spread and duration, can change from one seizure to the next within the same patient. However, the specific timescales of this variability, as well as the specific seizure characteristics that change over time, are unclear. Here, in a cross-sectional observational study, we analysed within-patient seizure variability in 10 patients with chronic intracranial EEG recordings (185-767 days of recording time, 57-452 analysed seizures atient). We characterised the seizure evolutions as sequences of a finite number of patient-specific functional seizure network states. We then compared seizure network state occurrence and duration to (1) time since implantation and (2) patient-specific circadian and multidien cycles in interictal spike rate. In most patients, the occurrence or duration of at least one seizure network state was associated with the time since implantation. Some patients had one or more seizure network states that were associated with phases of circadian and/or multidien spike rate cycles. A given seizure network state’s occurrence and duration were usually not associated with the same timescale. Our results suggest that different time-varying factors modulate within-patient seizure evolutions over multiple timescales, with separate processes modulating a seizure network state’s occurrence and duration. These findings imply that the development of time-adaptive treatments in epilepsy must account for several separate properties of epileptic seizures, and similar principles likely apply to other neurological conditions.
White Matter Changes in Patients with Parkinson's Disease Carrying Small CGG Expansion FMR1 Alleles: A Pilot Study
Publisher: S. Karger AG
Date: 24-12-2013
DOI: 10.1159/000356190
Abstract: b i Background/Aims: /i /b Alleles of the FMR1 gene containing small expansions of the CGG-trinucleotide repeat comprise premutation and grey-zone alleles. Premutation alleles may cause late-onset Fragile X-associated tremor/ataxia syndrome attributed to the neurotoxic effect of elevated FMR1 transcripts. Our earlier data suggested that both grey-zone and low-end premutation alleles might also play a significant role in the acquisition of the parkinsonian phenotype due to mitochondrial dysfunction caused by elevated FMR1 mRNA toxicity. These data were obtained through clinical and molecular comparisons between carriers of grey-zone/low-end premutation alleles and group-matched non-carrier controls from patients with idiopathic Parkinson's disease (iPD). We aimed to explore the relationship between grey-zone alleles, parkinsonism and white matter changes. b i Methods: /i /b This study compared the extent and severity of white matter hyperintensity (WMH) on magnetic resonance imaging, using a semi-quantitative method, between 11 grey-zone/low-end premutation carriers and 20 non-carrier controls with iPD from our earlier study. Relationships between WMH scores, and cognitive and motor test scores were assessed for carriers and non-carriers. b i Results: /i /b Supratentorial WMH scores i , /i and tremor and ataxia motor scores were significantly higher in carriers compared with disease controls. Moreover, some associations between cognitive decline and WMH scores were specific for each respective carrier status category. b i Conclusions: /i /b The results support our earlier claim that grey-zone alleles contribute to the severity of parkinsonism and white matter changes.
Consistency of Long-Term Subdural Electrocorticography in Humans
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2018
Rates of Event Capture of Ambulatory Video EEG
Publisher: Cold Spring Harbor Laboratory
Date: 14-11-2022
DOI: 10.1101/2022.11.13.22282197
Abstract: Recording electrographic and behavioral information during epileptic and other paroxysmal events is important during video EEG monitoring. This study was undertaken to measure the event capture rate of an ambulatory service operating across Australia using a shoulder-worn EEG device and telescopic pole-mounted camera. Neurologist reports were accessed retrospectively. Studies with confirmed events were identified and assessed for event capture by recording modality, whether events were reported or discovered, and wakefulness. 6,265 studies were identified, of which 2,788 (44.50%) had events. A total of 15,691 events were captured, of which 77.89% were reported. The EEG-ECG lifier was active for 99.83% of events. The patient was in view of the camera for 94.90% of events. 84.89% of studies had all events on camera, and 2.65% had zero events on camera (mean=93.66%, median=100.00%). 84.42% of events from wakefulness were reported, compared to 54.27% from sleep. Event capture was similar to previously reported rates from ambulatory studies, with higher capture rates on video. Most patients have all events captured on camera. Ambulatory monitoring is capable of high rates of event capture, and the use of wide-angle cameras allows for all events to be captured in the majority of studies. A review was undertaken of an Australia-wide ambulatory video-EEG monitoring service Patients were in view of camera for 94.90% of events, and 84.89% of studies had all events on camera 84.42% of events from wakefulness were reported, compared to 54.27% from sleep
Focal seizure symptoms in idiopathic generalized epilepsies
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-07-2015
Multiday cycles of heart rate are associated with seizure likelihood
Publisher: Cold Spring Harbor Laboratory
Date: 28-11-2020
DOI: 10.1101/2020.11.24.20237990
Abstract: Circadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology, and immunology. In people with epilepsy, epileptic brain activity and seizure occurrence have been found to follow circadian, weekly, and monthly rhythms. Understanding the relationship between these cycles of brain excitability and other physiological systems can provide new insight into the causes of multiday cycles. The brain-heart link is relevant for epilepsy, with implications for seizure forecasting, therapy, and mortality (i.e., sudden unexpected death in epilepsy). We report the results from a non-interventional, observational cohort study, Tracking Seizure Cycles. This study sought to examine multiday cycles of heart rate and seizures in adults with diagnosed uncontrolled epilepsy (N=31) and healthy adult controls (N=15) using wearable smartwatches and mobile seizure diaries over at least four months (M=12.0, SD=5.9 control M=10.6, SD=6.4). Cycles in heart rate were detected using a continuous wavelet transform. Relationships between heart rate cycles and seizure occurrence were measured from the distributions of seizure likelihood with respect to underlying cycle phase. Heart rate cycles were found in all 46 participants (people with epilepsy and healthy controls), with circadian (N=46), about-weekly (N=25) and about-monthly (N=13) rhythms being the most prevalent. Of the participants with epilepsy, 19 people had at least 20 reported seizures, and 10 of these had seizures significantly phase locked to their multiday heart rate cycles. Heart rate cycles showed similarities to multiday epileptic rhythms and may be comodulated with seizure likelihood. The relationship between heart rate and seizures is relevant for epilepsy therapy, including seizure forecasting, and may also have implications for cardiovascular disease. More broadly, understanding the link between multiday cycles in the heart and brain can shed new light on endogenous physiological rhythms in humans.
Temporal patterns of epileptiform discharges in genetic generalized epilepsies
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.YEBEH.2016.09.018
Abstract: We sought to investigate the temporal patterns and sleep-wake cycle-related epileptiform discharges (EDs) in genetic generalized epilepsies (GGEs). We studied 24-hour ambulatory electroencephalography (EEG) recordings of patients with GGE, diagnosed and classified according to the International League against Epilepsy criteria. We manually coded the type of discharge, time of occurrence, duration, and arousal state of each ED. We employed mixed effects Poisson regression modeling to study the temporal distribution of epileptiform discharges. Additionally, we used multinomial regression analysis to explore the significance of the relationship between different states of arousal and types of epileptiform discharges. We analyzed 6923 EDs from 105 abnormal 24-hour EEGs. Mixed effects Poisson regression analysis demonstrated significant changes in ED counts across time blocks. This distribution was largely influenced by the state of arousal. Generalized fragments (duration<2s) and focal discharges were more frequent during non-REM sleep while paroxysms (duration≥2s) were more frequent in wakefulness. Overall, 67% of epileptiform discharges occurred in non-REM sleep and only 33% occurred in wakefulness. Twenty-four patients (23%) had ED exclusively in sleep. Epileptiform discharges peaked from 23:00 through 07:00h. There is a time-of-day dependency of ED with a significant influence exerted by the state of arousal. Our observations suggest that the generation of epileptiform discharges is not a random process but is the result of complex interactions among biological rhythms such as the sleep-wake cycle and the intrinsic circadian pacemaker. High density of ED in sleep suggests that 24-hour EEG recording with the capture of natural sleep may be more useful than routine EEG to diagnose GGE.
Cerebral cortex: an MRI-based study of volume and variance with age and sex
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.JOCN.2005.02.013
Abstract: The aim of the present study was to examine quantitative differences in lobar cerebral cortical volumes in a healthy adult population. Quantitative volumetric MRI of whole brain, cerebral and cerebellar volumes was performed in a cross-sectional analysis of 97 normal volunteers, with segmented frontal, temporal, parietal and occipital cortical volumes measured in a subgroup of 60 subjects, 30 male and 30 female, matched for age and sex. The right cerebral hemisphere was larger than the left across the study group with a small (<1%) but significant difference in symmetry (P<0.001). No difference was found between volumes of right and left cerebellar hemispheres. Rightward cerebral cortical asymmetry (right larger than left) was found to be significant across all lobes except parietal. Males had greater cerebral, cerebellar and cerebral cortical lobar volumes than females. Larger male cerebral cortical volumes were seen in all lobes except for left parietal. Females had greater left parietal to left cerebral hemisphere and smaller left temporal to left cerebral hemisphere ratios. There was a mild reduction in cerebral volumes with age, more marked in males. This study confirms and augments past work indicating underlying structural asymmetries in the human brain, and provides further evidence that brain structures in humans are differentially sensitive to the effects of both age and sex.
Molecular and morphological analyses support recognition of Prostanthera volucris (Lamiaceae), a new species from the Central Tablelands of New South Wales
Publisher: CSIRO Publishing
Date: 08-02-2023
DOI: 10.1071/SB22017
Abstract: Research into the systematics of Prostanthera recently revealed close evolutionary relationship among P. phylicifolia sens. str., the critically endangered P. gilesii, and a population of uncertain identity from the Central Tablelands of New South Wales (NSW), Australia. Previous analyses were unable to establish whether genetic boundaries separated these taxa. This study assessed species boundaries among these three taxa by using a combination of single-nucleotide polymorphisms (SNPs) s led at the population-scale and multivariate analysis of morphological characters. Ordination, model-based clustering, F-statistics, neighbour-network analysis, phylogenetic analysis, and ancestry coefficient estimates all provided support for discrete genetic differences among the three taxa. Morphological phenetic analysis recovered congruent morphological clusters and identified a suite of corresponding diagnostic characters. This congruence of molecular and morphological evidence supports the presence of three independently evolving lineages, two of which correspond with the previously described P. gilesii and P. phylicifolia sens. str. The third taxon, represented by a single population from the Central Tablelands of NSW, is here described as P. volucris R.P.O’Donnell. A detailed description, diagnostic line drawings and photographs are provided. We evaluate P. volucris as satisfying criteria to be considered Critically Endangered.
Reply: Transcranial magnetic stimulation as a biomarker for epilepsy.
Publisher: Oxford University Press (OUP)
Date: 24-02-2017
DOI: 10.1093/BRAIN/AWW346
Patient-specific bivariate-synchrony-based seizure prediction for short prediction horizons
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.EPLEPSYRES.2010.07.014
Abstract: This paper evaluates the patient-specific seizure prediction performance of pre-ictal changes in bivariate-synchrony between pairs of intracranial electroencephalographic (iEEG) signals within 15min of a seizure in patients with pharmacoresistant focal epilepsy. Prediction horizons under 15min reduce the durations of warning times and should provide adequate time for a seizure control device to intervene. Long-term continuous iEEG was obtained from 6 patients. The seizure prediction performance was evaluated for all possible channel pairs and for different prediction methods to find the best performing channel pairs and methods for both pre-ictal decreases and increases in synchrony. The different prediction methods involved changes in window duration, signal filtering, thresholding approach, and prediction horizon durations. Performance for each patient, for all seizures, was first compared with an analytical-Poisson-based random predictor. The performance of the top 5% of channel pairs for each patient closely matched the top 5% of analytical-Poisson-based random predictor performance indicating that patient-specific, bivariate-synchrony-based seizure prediction could be random in general (under the assumption that channel-pair prediction times are statistically independent). Analysis of the spatial patterns of performance showed no clear relationship to the seizure onset zone. For each patient the best channel pair showed better performance than Poisson-based random prediction for a selected subset of prediction thresholds. Given the caveats of comparing with this form of random prediction, alarm time surrogates were employed to assess statistical significance of a four-fold out-of-s le cross-validation analysis applied to the best channel-pairs. The cross-validation analysis obtained reasonable testing performance for most patients when performance was compared to random prediction based on alarm time surrogates. The most significant case was a patient whose testing set sensitivity and false positive rate were 0.67±0.09 and 3.04±0.29h(-1), respectively, for decreases in synchrony, an intervention time of 15min and a seizure onset period of 5min. For each testing set for this patient, performance was better than that obtained by random prediction at the significance level of 0.05 (average sensitivity of 0.47±0.05). Moreover, there were 9 seizures in each testing set which gives greater power to this cross-validation result, although the cross-validation was performed on the best channel pair selected by within-s le optimization for all seizures of the patient. Further validation with larger datasets from in idual patients is needed. Improvements in prediction performance should be achievable through investigations of multivariate synchrony combined with non-linear classification methods.
A low symptomatic form of neurodegeneration in younger carriers of the FMR1 premutation, manifesting typical radiological changes
Publisher: BMJ
Date: 22-10-2007
Abstract: Fragile X-associated tremor/ataxia (FXTAS) is a late onset disorder caused by a premutation in the FMR1 gene, in which neurological symptoms are associated with white matter (wm) changes, especially within the middle cerebellar peduncles (MCP sign), seen on magnetic resonance images (MRIs). We report a discrepancy between obvious radiological presentations and minimal clinical involvement in two younger male premutation carriers. These carriers, aged 52 and 39 years, showed distinct MCP sign, but reported no neurological symptoms. If this discrepancy represents the initial stage of FXTAS, our findings suggest the possibility of early diagnosis from MRI scans.
A taxonomy of seizure dynamotypes
Publisher: eLife Sciences Publications, Ltd
Date: 21-07-2020
DOI: 10.7554/ELIFE.55632
Abstract: Seizures are a disruption of normal brain activity present across a vast range of species and conditions. We introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory. The ‘dynamotype’ of a seizure is the dynamic composition that defines its observable characteristics, including how it starts, evolves and ends. Analyzing over 2000 focal-onset seizures from multiple centers, we find evidence of all 16 dynamotypes predicted in TSD. We demonstrate that patients’ dynamotypes evolve during their lifetime and display complex but systematic variations including hierarchy (certain types are more common), non-bijectivity (a patient may display multiple types) and pairing preference (multiple types may occur during one seizure). TSD provides a way to stratify patients in complement to present clinical classifications, a language to describe the most critical features of seizure dynamics, and a framework to guide future research focused on dynamical properties.
Global expression profiling in epileptogenesis: does it add to the confusion?
Publisher: Wiley
Date: 07-12-2010
Single-fiber F waves compared with conventional surface F waves, and their utility in detecting early diabetic neuropathy
Publisher: Wiley
Date: 19-09-2018
DOI: 10.1002/MUS.26290
Abstract: The single-fiber F-wave (SFF-wave) technique assesses the entire length of single motor fibers using a concentric needle. Herein we investigated the utility of this approach in the detection of early diabetes-related neuropathy, and compared it with the use of conventional surface F waves (CF waves). Sixteen patients with diabetes and either no neuropathy or mild neuropathy were assessed and compared with 16 age- and height-matched control participants. Both CF and SFF waves were abnormal in all 5 patients who had mild neuropathy. However, SFF waves demonstrated subclinical abnormalities in 7 of 11 patients (64%) with no neuropathy, whereas only 2 of these patients (18%) had prolonged CF waves. Minimum F-wave latency was comparable between techniques, but maximum SFF-wave latency was more frequently prolonged, as these delayed motor units were better isolated, rather than buried among summated CF-wave responses. SFF waves highlight the segmental involvement in diabetic neuropathy, and use of the SFF-wave technique detects more abnormalities than with CF waves. Muscle Nerve 58: 665-670, 2018.
451: Painting dreams shaped by epilepsy and the auras of migraines
Publisher: Elsevier BV
Date: 03-2008
Controlled delivery for neuro-bionic devices
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.ADDR.2012.06.002
Abstract: Implantable electrodes interface with the human body for a range of therapeutic as well as diagnostic applications. Here we provide an overview of controlled delivery strategies used in neuro-bionics. Controlled delivery of bioactive molecules has been used to minimise reactive cellular and tissue responses and/or promote nerve preservation and neurite outgrowth toward the implanted electrode. These effects are integral to establishing a chronically stable and effective electrode-neural communication. Drug-eluting bioactive coatings, organic conductive polymers, or integrated microfabricated drug delivery channels are strategies commonly used.
Critical slowing down as a biomarker for seizure susceptibility
Publisher: Springer Science and Business Media LLC
Date: 05-2020
DOI: 10.1038/S41467-020-15908-3
Abstract: The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.
Temporal lobe epilepsy caused by mesial temporal sclerosis and temporal neocortical lesions. A clinical and electroencephalographic study of 46 pathologically proven cases
Publisher: Oxford University Press (OUP)
Date: 1996
Abstract: This study aims to determine whether there are important clinico-electrical differences between patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete temporal neocortical lesion (NL). The case histories, interictal EEG, seizure semiology, ictal EEG and postoperative outcome of 46 pathologically proven patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC) was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There were no statistically significant differences in the incidence or nature of auras. No statistically significant differences between the groups were found in the interictal-EEG. With ictal semiology dystonic posturing occurred more frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/ twitching occurred earlier in the seizures of NL patients (median 19 s versus 35 s, P 4 Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The patients with NL developed bilateral ictal EEG changes more often (mean 55% versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The onset of ictal EEG seizure activity was bilateral more often in patients with NL (20% versus 4%, P < 0.005). There were no significant differences between the two groups for any of the video-EEG features, in terms of whether or not the feature occurred at least once in an in idual patients. There was a tendency for MTS patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P = 0.057). However, all the NL patients who were not free of seizures had had an incomplete lesion resection. We conclude that there are a number of clinico-electrical differences between patients with mesial TLE (MTLE) and patients with neocortical TLE (NCTLE), but that none of these are sufficient to allow a distinction to be made in an in idual patient.
Cycles of self-reported seizure likelihood correspond to yield of diagnostic epilepsy monitoring
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2020
DOI: 10.1101/2020.10.05.20207407
Abstract: Objective: Video-electroencephalography (vEEG) is an important component of epilepsy diagnosis and management. Nevertheless, inpatient vEEG monitoring fails to capture seizures in up to one third of patients during diagnostic and pre-surgical monitoring. We hypothesized that personalized seizure forecasts could be used to optimize the timing of vEEG and improve diagnostic yield. Methods: We used a database of ambulatory vEEG studies to select a cohort with linked electronic seizure diaries of more than 20 reported seizures over at least 8 weeks. The total cohort included 48 participants. Diary seizure times were used to detect in iduals' multi-day cycles and estimate times of high seizure risk. We then compared whether estimated seizure risk was significantly different between diagnostic and non-diagnostic vEEGs, and between vEEG with and without recorded epileptic activity. Results: Estimated seizure risk was significantly higher for diagnostic vEEGs and vEEGs with epileptic activity. Across all cycle strengths, the average time in high risk during vEEG was 29.1% compared with 14% for the diagnostic/non-diagnostic groups and 32% compared to 18% for the epileptic activity/no epileptic activity groups. On average, 62.5% of the cohort showed increased time in high risk during vEEG when epileptic activity was recorded (compared to 28% of the cohort where epileptic activity was not recorded). For diagnostic vEEGs, 50% of the cohort had increased time in high risk, compared to 21.5% for non-diagnostic vEEGs. Significance: This study provides a proof of principle that scheduling monitoring times based on personalized seizure risk forecasts can improve the yield of vEEG. Importantly, forecasts can be developed at low cost from mobile seizure diaries. A simple scheduling tool to improve diagnostic outcomes has the potential to reduce the significant cost and risks associated with delayed or missed diagnosis in epilepsy.
Specificity of psychopathology in temporal lobe epilepsy
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.YEBEH.2012.12.026
Abstract: An investigation into the specificity of psychopathology in temporal lobe epilepsy was conducted using the Minnesota Multiphase Personality Inventory second edition (MMPI-2) profiles. Consecutive series of patients with left temporal lobe epilepsy (n = 49) and those with right temporal lobe epilepsy (n = 45) were compared with patients with other forms of epilepsy (n = 46) and other heterogeneous neurological conditions (n = 69). The investigation focused on the Clinical, Content, and Subscales scales that resembled descriptions of the Interictal Dysphoric Disorder symptoms and Temporal Lobe Epilepsy Personality Traits. Patients with right temporal lobe epilepsy and those with left temporal lobe epilepsy did not have different patterns of scale elevation, nor did they have clinical elevations compared with patients with other types of epilepsy or neurological controls. The MMPI-2 scales that resemble descriptions of the Interictal Dysphoric Disorder or Temporal Lobe Epilepsy Personality Syndrome were not elevated in either group of patients with temporal lobe epilepsy compared with the group of patients with non-temporal lobe epilepsy or heterogeneous neurological controls. This study adds to the mounting body of empirical research that has used standardized measures and matched groups, but failed to detect a special affinity between psychopathology and temporal lobe epilepsy.
Rhinal cortex asymmetries in patients with mesial temporal sclerosis
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.SEIZURE.2007.07.010
Abstract: The rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices, is one component of the limbic system that may be affected in patients with epilepsy and other temporal lobe pathologies. This study extended quantitative examination of the limbic system through development and validation of volumetric protocols to measure the ErC and PrC. Volumes were calculated from MRI studies using ANALYZE 7.5 and based on detailed anatomical definitions developed for the study. Subjects were 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS: 33 left, 28 right) and 20 neurologically normal controls. Inter-rater reliabilities for the ErC and PrC volume protocols were found to be high (range 0.86-0.92). Ipsilateral hippoc al volume was reduced in patients with MTS, while contralateral volume did not differ significantly from controls. In the patients, rhinal cortex volumes were reduced as a function of laterality of disease. The pattern of correlations between ErC and PrC differed between disease groups. Hippoc al and rhinal cortex volumes were not significantly correlated. A significant four-way interaction was found between side of MTS, hemisphere, structure and handedness. This quantitative study demonstrates reliable in vivo evidence of morphometric changes in ErC and PrC in a substantial number of patients with unilateral MTS. The relationship observed between handedness, structure and disease status may suggest a role for cerebral dominance in modulating the expression of MTS.
Wernicke-Korsakoff syndrome not related to alcohol use: a systematic review
Publisher: BMJ
Date: 14-01-2015
Abstract: Although Wernicke-Korsakoff syndrome (WKS) is a common condition, diagnosis remains difficult. WKS not associated with alcohol is rare and thought to present differently to alcohol-related WKS. We conducted a systematic review of WKS not related to alcohol to enhance understanding of WKS not related to alcohol and WKS in general. A systematic review was conducted of case reports, published in English, of Wernicke's encephalopathy and WKS in patients without a history of alcohol-use disorder. Main data sources: MEDLINE, Index Medicus. Eligible cases totaled 623. Publication dates ranged from 1867 to 2014. Comparisons of clinical presentation were made with published data on s les comprising, almost exclusively, alcohol-related WKS. A wide array of illnesses precipitated WKS. When diagnosis of WKS was performed postmortem, non-alcohol-related cases presented a similar number of signs of the classic triad as alcohol-related cases (p=0.662, Cohen's w=0.12) but more signs when diagnosed antemortem (p<0.001, Cohen's w=0.46). The most common sign was altered mental state. Korsakoff syndrome or ongoing memory impairment was reported in 25% of non-alcohol-related WKS, although cognitive status was not explicitly reported in many cases. When duration of memory impairment was reported, 56% had clinically obvious memory impairment lasting beyond the period of acute presentation. Non-alcohol-related WKS was more often associated with female gender, younger age, shorter duration of precipitating illness and better survival rate compared to alcohol-related WKS. Thiamine deficiency in the absence of an alcohol-use disorder can cause the full clinical spectrum of WKS, including chronic cognitive impairment and Korsakoff syndrome.
Intravascular large B-cell lymphoma occurring 25 years after treatment of ALK-positive anaplastic large cell lymphoma
Publisher: Informa UK Limited
Date: 30-04-2013
A neural mass model of spontaneous burst suppression and epileptic seizures
Publisher: IEEE
Date: 07-2013
Amygdala volumetry in imaging-negative temporal lobe epilepsy
Publisher: BMJ
Date: 09-2003
Abstract: Although amygdala abnormalities are sometimes suspected in "imaging-negative" patients with video EEG confirmed unilateral focal epilepsy suggestive of temporal lobe epilepsy (TLE), amygdala asymmetry is difficult to assess visually. This study examined a group of "imaging-negative" TLE patients, estimating amygdala volumes, to determine whether cryptic amygdala lesions might be detected. Review of video EEG monitoring data yielded 11 patients with EEG lateralised TLE and normal structural imaging. Amygdala volumes were estimated in this group, in 77 patients with pathologically verified hippoc al sclerosis (HS), and in 77 controls. Seven of 11 "imaging-negative" cases had both significant amygdala asymmetry and amygdala enlargement, concordant with seizure lateralisation. Although significant amygdala asymmetry occurred in 35 of 77 HS patients, it was never attributable to an abnormally large ipsilateral amygdala. Compared with patients with HS, patients with amygdala enlargement were less likely to have suffered secondarily generalised seizures (p<0.05), and had an older age of seizure onset (p<0.01). Abnormal amygdala enlargement is reported in seven cases of "imaging-negative" TLE. Such abnormalities are not observed in patients with HS. It is postulated that amygdala enlargement may be attributable to a developmental abnormality or low grade tumour. It is suggested that amygdala volumetry is indicated in the investigation and diagnosis of "imaging-negative" TLE.
Bursts of seizures in long-term recordings of human focal epilepsy
Publisher: Wiley
Date: 13-01-2017
DOI: 10.1111/EPI.13636
Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle
Publisher: Proceedings of the National Academy of Sciences
Date: 09-11-2015
Abstract: Dynamic changes of cortical excitability are relevant in both healthy and pathological network dynamics. In epilepsy, pathological changes in excitability commonly underlie the initiation and spread of seizures. Accordingly, the ability to monitor excitability and control its degree is important for adequate clinical care and treatment because classic EEG markers found in epilepsy such as interictal spikes do not reflect seizure propensity and thus excitability. Here, we identify excitability markers and test them on long-term electrocorticogram and EEG recordings. We show that they correlate with more direct excitability measures using external stimulation and allow for real-time excitability monitoring. Our results provide evidence that excitability of cortical networks is reduced by antiepileptic drugs and increases as a function of time awake.
Australian Pregnancy Registry of Women Taking Antiepileptic Drugs
Publisher: Wiley
Date: 27-10-2004
Oxford Textbook of Epilepsy and Epileptic Seizures
Publisher: Oxford University Press
Date: 12-2012
Subcortical epilepsy?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-05-2013
Seizure pathways: A model-based investigation
Publisher: Public Library of Science (PLoS)
Date: 11-10-2018
The structural connectome in traumatic brain injury: A meta-analysis of graph metrics
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.NEUBIOREV.2019.01.002
Abstract: Although recent structural connectivity studies of traumatic brain injury (TBI) have used graph theory to evaluate alterations in global integration and functional segregation, pooled analysis is needed to examine the robust patterns of change in graph metrics across studies. Following a systematic search, 15 studies met the inclusion criteria for review. Of these, ten studies were included in a random-effects meta-analysis of global graph metrics, and subgroup analyses examined the confounding effects of severity and time since injury. The meta-analysis revealed significantly higher values of normalised clustering coefficient (gö=ö1.445, CI=[0.512, 2.378], pö=ö0.002) and longer characteristic path length (gö=ö0.514, CI=[0.190, 0.838], pö=ö0.002) in TBI patients compared with healthy controls. Our findings suggest that the TBI structural network has shifted away from the balanced small-world network towards a regular lattice. Therefore, these graph metrics may be useful markers of neurocognitive dysfunction in TBI. We conclude that the pattern of change revealed by our analysis should be used to guide hypothesis-driven research into the role of graph metrics as diagnostic and prognostic biomarkers.
Electrical probing of cortical excitability in patients with epilepsy
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.YEBEH.2011.09.005
Abstract: Standard methods for seizure prediction involve passive monitoring of intracranial electroencephalography (iEEG) in order to track the 'state' of the brain. This paper introduces a new method for measuring cortical excitability using an electrical probing stimulus. Electrical probing enables feature extraction in a more robust and controlled manner compared to passively tracking features of iEEG signals. The probing stimuli consist of 100 bi-phasic pulses, delivered every 10 min. Features representing neural excitability are estimated from the iEEG responses to the stimuli. These features include the litude of the electrically evoked potential, the mean phase variance (univariate), and the phase-locking value (bivariate). In one patient, it is shown how the features vary over time in relation to the sleep-wake cycle and an epileptic seizure. For a second patient, it is demonstrated how the features vary with the rate of interictal discharges. In addition, the spatial pattern of increases and decreases in phase synchrony is explored when comparing periods of low and high interictal discharge rates, or sleep and awake states. The results demonstrate a proof-of-principle for the method to be applied in a seizure anticipation framework. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.
Depression in Temporal Lobe Epilepsy Surgery Patients: An FDG‐PET Study
Publisher: Wiley
Date: 28-11-2006
DOI: 10.1111/J.1528-1167.2006.00860.X
Abstract: Depression is common in temporal lobe epilepsy (TLE) and after temporal lobectomy, and its etiology is obscure. In nonepileptic depression (including depression associated with other neurologic disorders), a consistent PET imaging finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism involving frontal regions. Thus in data available from routine clinical assessments in an epilepsy surgery unit, we tested the hypothesis that the pattern of hypometabolism, particularly in the frontal lobe, may be associated with the depression seen in patients with TLE and TLE surgery. We studied 23 medically refractory TLE patients who underwent anterior temporal lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and postoperative psychiatric assessment. By using statistical parametric mapping (SPM-99), patterns of hypometabolism were compared between patients who had a preoperative history of depression (n=9) versus those who did not (n=14) and between those in whom postoperative depression developed (n=13) versus those in whom it did not (n=10). A significant region of hypometabolism was set at p or=20 contiguous voxels. Patients with a history of depression at any time preoperatively showed focal hypometabolism in ipsilateral orbitofrontal cortex compared with those who did not (t=4.64 p<0.001). Patients in whom depression developed postoperatively also showed hypometabolism in the ipsilateral orbitofrontal region (t=5.10 p<0.001). Although this study is methodologically limited, and other explanations merit consideration, orbitofrontal cortex dysfunction, already implicated in the pathophysiology of nonepileptic depression, may also be relevant to the depression of TLE and temporal lobectomy.
Cortical excitability changes correlate with fluctuations in glucose levels in patients with epilepsy
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.YEBEH.2013.03.015
Abstract: We used transcranial magnetic stimulation (TMS) to investigate motor cortical excitability changes in relation to blood glucose levels. Twenty-two drug-naïve patients with epilepsy [11 generalized and 11 focal] and 10 controls were studied twice on the same day first after 12h of fasting and then 2h postprandial. Motor threshold and paired-pulse TMS at a number of short and long interstimulus intervals were measured. Serum glucose levels were measured each time. Decreased long intracortical inhibition was seen in patients and controls during fasting compared to postprandial studies. This effect was much more prominent in patients with generalized epilepsy (with effect sizes of up to 0.8) in whom there was also evidence of increased intracortical facilitation (effect size: 0.3). Cortical excitability varies with fluctuations in blood glucose levels. This variation is more prominent in patients with epilepsy. Decreased glucose levels may be an important physiological seizure trigger.
When can we trust responders? Serious concerns when using 50% response rate to assess clinical trials.
Publisher: Wiley
Date: 31-08-2019
DOI: 10.1111/EPI.16321
Abstract: In idual seizure rates are highly volatile, with large fluctuations from month-to-month. Nevertheless, changes in in idual mean seizure rates are used to measure whether or not trial participants successfully respond to treatment. This study aims to quantify the challenges in identifying in idual treatment responders in epilepsy. A power calculation was performed to determine the trial duration required to detect a significant 50% decrease in seizure rates (P < .05) for in iduals. Seizure rate simulations were also performed to determine the number of people who would appear to be 50% responders by chance. Seizure rate statistics were derived from long-term seizure counts recorded during a previous clinical trial for an implantable seizure monitoring device. We showed that in idual variance in monthly seizure rates can lead to an unacceptably high false-positive rate in the detection of in idual treatment responders. This error rate cannot be reduced by increasing the trial population however, it can be reduced by increasing the duration of clinical trials. This finding suggests that some drugs may be incorrectly evaluated as effective or, conversely, that helpful drugs could be rejected based on 50% response rates. It is important to pursue more nuanced approaches to measuring in idual treatment response, which consider the patient-specific distributions of seizure rates.
Differential Diagnosis of Epilepsy
Publisher: Wiley
Date: 02-10-2015
Are the days of counting seizures numbered?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
Human focal seizures are characterized by populations of fixed duration and interval
Publisher: Wiley
Date: 31-12-2016
DOI: 10.1111/EPI.13291
Abstract: We report on a quantitative analysis of data from a study that acquired continuous long-term ambulatory human electroencephalography (EEG) data over extended periods. The objectives were to examine the seizure duration and interseizure interval (ISI), their relationship to each other, and the effect of these features on the clinical manifestation of events. Chronic ambulatory intracranial EEG data acquired for the purpose of seizure prediction were analyzed and annotated. A detection algorithm identified potential seizure activity, which was manually confirmed. Events were classified as clinically corroborated, electroencephalographically identical but not clinically corroborated, or subclinical. K-means cluster analysis supplemented by finite mixture modeling was used to locate groupings of seizure duration and ISI. Quantitative analyses confirmed well-resolved groups of seizure duration and ISIs, which were either mono-modal or multimodal, and highly subject specific. Subjects with a single population of seizures were linked to improved seizure prediction outcomes. There was a complex relationship between clinically manifest seizures, seizure duration, and interval. These data represent the first opportunity to reliably investigate the statistics of seizure occurrence in a realistic, long-term setting. The presence of distinct duration groups implies that the evolution of seizures follows a predetermined course. Patterns of seizure activity showed considerable variation between in iduals, but were highly predictable within in iduals. This finding indicates seizure dynamics are characterized by subject-specific time scales therefore, temporal distributions of seizures should also be interpreted on an in idual level. Identification of duration and interval subgroups may provide a new avenue for improving seizure prediction.
Toothbrushing-induced epilepsy with structural lesions in the primary somatosensory area
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-03-2007
DOI: 10.1212/01.WNL.0000256375.39476.BE
Abstract: We report three patients with reflex toothbrushing-induced epilepsy associated with small circumscribed structural lesions in the primary somatosensory cortex in close proximity to the hand and speech motor areas. Sensory symptoms were observed at clinical onset with localizing focal ictal and interictal epileptiform discharges on EEG. These cases refine the localization, possible mechanisms of epileptogenesis, and classification of this reflex epilepsy.
Deep brain stimulation for drug-resistant epilepsy.
Publisher: Wiley
Date: 07-12-2018
DOI: 10.1111/EPI.13964
Abstract: To review clinical evidence on the antiepileptic effects of deep brain stimulation (DBS) for drug-resistant epilepsy, its safety, and the factors influencing in idual outcomes. A comprehensive search of the medical literature (PubMed, Medline) was conducted to identify relevant articles investigating DBS therapy for drug-resistant epilepsy. Reference lists of these articles were used to source further articles. Stimulation of the anterior nucleus of the thalamus (ANT) and hippoc us (HC) has been shown to decrease the frequency of refractory seizures. Half of all patients from clinical studies experienced a 46%-90% seizure reduction with ANT-DBS, and a 48%-95% seizure reduction with HC-DBS. The efficacy of stimulating other targets remains inconclusive due to lack of evidence. Approximately three-fourths of patients receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are responders-experiencing a seizure reduction of at least 50%. The time course of clinical benefit varies dramatically, with both an initial lesional effect and ongoing stimulation effect at play. Improved quality of life and changes to cognition or mood may also occur. Side effects are similar in nature to those reported from DBS therapy for movement disorders. Several factors are potentially associated with stimulation efficacy, including an absence of structural abnormality on imaging for ANT and HC stimulation, and electrode position relative to the target. Certain seizure types or syndromes may respond more favorably to specific targets, including ANT stimulation for deep temporal or limbic seizures, and CMT stimulation for generalized seizures and Lennox-Gastaut syndrome. We have identified several patient, disease, and stimulation factors that potentially predict seizure outcome following DBS. More large-scale clinical trials are needed to explore different stimulation parameters, reevaluate the indications for DBS, and identify robust predictors of patient response.
Combining cutaneous silent periods with quantitative sudomotor axon reflex testing in the assessment of diabetic small fiber neuropathy
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.CLINPH.2014.09.011
Abstract: Routine electrophysiological testing is often normal in the evaluation of painful diabetic neuropathy, as it is unable to detect dysfunction of thinly myelinated (Aδ) and unmyelinated (C) small fibers. Although cutaneous silent periods (CSP) and quantitative sudomotor axon reflex testing (QSART) respectively evaluate these fiber types in the extremities, these two tests have yet to be assessed together. 26 patients with a clinical diagnosis of small fiber neuropathy (SFN) and 26 age-matched controls were assessed. Nine patients had Type I diabetes, nine had Type II diabetes, and eight had impaired glucose tolerance. The CSP onset latency and duration were recorded in each extremity. QSART was performed on the right side. 58% (15/26) of patients had abnormal sweat volumes obtained from QSART, while 50% (13/26) of patients had abnormal CSP responses. Combining these two tests increased the sensitivity of testing to 77% (20/26). Abnormalities were seen equally across all patient groups. Combining CSP with QSART significantly increases the sensitivity of testing when assessing patients with SFN related to diabetes, or prediabetes. For clinically suspected SFN, it is preferable to test more than one small fiber type, as each possess different structural and functional properties and may be heterogeneously affected between patients.
Isolated amygdala enlargement in temporal lobe epilepsy: A systematic review
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.YEBEH.2016.04.015
Abstract: The objective of this study was to compare the seizure characteristics and treatment outcomes in patient groups with temporal lobe epilepsy (TLE) identified with isolated amygdala enlargement (AE) on magnetic resonance imaging studies. PubMed, Embase, and the Cochrane Library were searched for relevant studies using the keywords 'amygdala enlargement', 'epilepsy', and 'seizures' in April 2015. Human studies, written in English, that investigated cohorts of patients with TLE and AE were included. Of 204 abstracts initially identified using the search strategy, 14 studies met the inclusion criteria (11 epilepsy studies and 3 psychiatry studies). Ultimately, 8 full studies on AE and TLE involving 107 unique patients were analyzed. Gender distribution consisted of 50 males and 57 females. Right amygdala enlargement was seen in 39 patients, left enlargement in 58 patients, and bilateral enlargement in 7 patients. Surgical resection was performed in 28 patients, with the most common finding being dysplasia/hamartoma or focal cortical dysplasia. Most studies involved small s les of less than 12 patients. There was a wide discrepancy in the methods used to measure amygdala volume, in both patients and controls, hindering comparisons. Most TLE with AE studies observed a later age of seizure onset (mean: 32.2years) compared with studies involving TLE with HS (mean of mid- to late childhood). A higher frequency of complex partial seizures compared with that of convulsive seizures is seen in patients with AE (67-100% vs. 26-47%), and they have an excellent response to antiepileptic drugs (81.8%-100% of seizure-free patients). All studies that included controls also found a significant difference in frequency of seizure types between their cases and controls. Reliable assessment of amygdala volume remains a critical issue hindering better understanding of the clinical management and research of this focal epilepsy syndrome. Within these limitations, the literature suggests characteristics of an older age of epilepsy onset, a greater tendency to nonconvulsive seizures, and a good response to antiepileptic drugs in this interesting group of epilepsies.
The Effects of Closed-Loop Brain Implants on Autonomy and Deliberation
Publisher: Cambridge University Press (CUP)
Date: 06-03-2018
DOI: 10.1017/S0963180117000640
Abstract: A new generation of implantable brain–computer interfaces (BCI) devices have been tested for the first time in a human clinical trial, with significant success. These intelligent implants detect specific neuronal activity patterns, such as an epileptic seizure, and provide information to help patients to respond to the upcoming neuronal events. By forecasting a seizure, the technology keeps patients in the decisional loop the device gives control to patients on how to respond and decide on a therapeutic course ahead of time. Being kept in the decisional loop can positively increase patients’ quality of life however, doing so does not come free of ethical concerns. There is currently a lack of evidence concerning the various impacts of closed-loop system BCIs on patients’ decisionmaking processes, especially how being in the decisional loop impacts patients’ sense of autonomy. This article addresses these gaps by providing data that we obtained from a first-in-human clinical trial involving patients implanted with advisory brain devices. This article explores ethical issues related to the risks involved in being kept in the decisional loop.
Is seizure frequency variance a predictable quantity?
Publisher: Wiley
Date: 09-01-2018
DOI: 10.1002/ACN3.519
Evaluation of an automated spike-and-wave complex detection algorithm in the EEG from a rat model of absence epilepsy
Publisher: Springer Science and Business Media LLC
Date: 04-08-2015
Effects of a common transcranial direct current stimulation (tDCS) protocol on motor evoked potentials found to be highly variable within individuals over 9 testing sessions.
Publisher: Springer Science and Business Media LLC
Date: 05-05-2016
DOI: 10.1007/S00221-016-4667-8
Abstract: Transcranial direct current stimulation (tDCS) uses a weak electric current to modulate neuronal activity. A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials (MEPs). Here, we conduct a study testing the reliability of in idual MEP response patterns following a common tDCS protocol. Fourteen participants (7m/7f) each underwent nine randomized sessions of 1 mA, 10 min tDCS (3 anode 3 cathode 3 sham) delivered using an M1/orbito-frontal electrode montage (sessions separated by an average of ~5.5 days). Fifteen MEPs were obtained prior to, immediately following and in 5 min intervals for 30 min following tDCS. TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization. A number of non-experimental variables were collected during each session. At the in idual level, considerable variability was seen among different testing sessions. No participant demonstrated an excitatory response ≥20 % to all three anodal sessions, and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions. Intra-class correlation revealed poor anodal and cathodal test-retest reliability [anode: ICC(2,1) = 0.062 cathode: ICC(2,1) = 0.055] and moderate sham test-retest reliability [ICC(2,1) = 0.433]. Results also revealed no significant effect of tDCS at the group level. Using this common protocol, we found the effects of tDCS on MEP litudes to be highly variable at the in idual level. In addition, no significant effects of tDCS on MEP litude were found at the group level. Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-in idual response variations.
Reliability and validity of the CogState computerized battery in patients with seizure disorders and healthy young adults: comparison with standard neuropsychological tests.
Publisher: Informa UK Limited
Date: 17-11-2016
DOI: 10.1080/13854046.2016.1256435
Abstract: The aim was to examine the reliability and validity of two measures of learning and memory within the CogState Computerized Battery: the One Card Learning (OCL) and the Continuous Paired Associative Learning (CPAL). Comparison of various reliable change measures was also included to examine rate of correct cognitive change classification, in particular, when using the Within-Subject Standard Deviation (WSD). The OCL and the CPAL tests were administered twice and compared to standard and experimental versions of conventional neuropsychological tests in patients with seizure disorders (Baseline n = 80, Follow-up = 54) and university students (Baseline n = 89, Follow-up n = 87). Calculations of Reliable Change Indices (RCIs) on in idual performance were obtained to detect reliable change across time using published CogState and current study parameters. Results showed low retest reliabilities in both OCL and CPAL tests (r's = .49-.77). Small to medium convergent validity correlations with traditional tests of learning and working memory were also found. Discrepancies in RCIs methods on performance estimation were observed when different test parameters and reliabilities were used. In contrast to recent recommendations by publishers of the CogState tests, the WSD method was found to substantially increase the rate of Type-I error when tests reliabilities were low. Unsatisfactory reliability and validity estimates suggest caution regarding the CogState computerized measures of learning and memory as opposed to conventional tests. Caution should be used when interpreting OCL and CPAL test scores, as confidence intervals may be wide and encompass much of the population range. In line with previous recommendations, use of the WSD to detect change in performance over time should be avoided in neuropsychological testing, as this change measure is prone to elevated misclassification rates compared to other methods. Further independent research is needed to improve the psychometrics of CogState OCL and CPAL measures.
Seizure frequency and duration of epilepsy are not risk factors for postoperative seizure outcome in patients with hippocampal sclerosis
Publisher: Wiley
Date: 07-1999
DOI: 10.1111/J.1528-1157.1999.TB00796.X
Abstract: Despite accurate localization of the seizure focus, not all patients are seizure free after temporal lobectomy. This study determined risk factors for seizure recurrence in patients with proven hippoc al sclerosis. The outcome from surgery was assessed in 56 consecutive patients with proven hippoc al sclerosis. The age at surgery, duration of epilepsy, history and age of febrile seizures, age of onset of epilepsy, sex ratio, laterality of seizure focus, and seizure frequency were compared between patients seizure free and those not seizure free, and those seizure and aura free and those with seizure recurrence including auras. During a mean follow-up of 38 months, 48 (86%) of 56 are seizure free. The mean age at surgery (37 vs. 36 years), duration of epilepsy (26 vs. 22 years), age (1.6 vs. 1.1 years), and occurrence (58 vs. 75%) of febrile seizures, age of onset of epilepsy (11 vs. 14 years), sex ratio (50 vs. 75% female), laterality of seizure focus (42 vs. 50% left), greater than weekly seizures (40 vs. 38%), and a history of (69 vs. 75%) and frequency of (2.10 vs. 2.38 per year) secondarily generalized seizures did not differ significantly between the two groups. Similarly there was no significant difference between patients seizure and aura free and those with seizure recurrence including auras. Clinical factors such as seizure frequency and duration of epilepsy are not risk factors for postoperative seizure recurrence.
“A Twist in the Tale” of a Surgeon and his Patient: An Australian First in Seizure Localization
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/09647040600792622
Abstract: In 1894 at St. Vincent's Hospital Melbourne, George Adlington Syme removed a meningioma from a patient with symptomatic focal epilepsy. The operation stands as the first surgery based on seizure localization in Australia. It is also the country's first documented successful resection of an intracranial meningioma. It followed William Macewen's landmark cerebral localization case on the boy John McKinley by 18 years and Victor Horsley's first epilepsy case on Hughlings Jackson's patient James B. by a mere 8 years. Syme's patient, Constable John G., survived the operation by some 23 years, dying from a gunshot wound to the head in 1917. Newly discovered inquest papers reveal that the coroner's judgment that the death was accidental completely fails to address the more credible scenario of suicide. The story makes for a fascinating epilogue to an important landmark in Australia's neurosurgical history.
Deep learning for automated detection of generalized paroxysmal fast activity in Lennox–Gastaut syndrome
Publisher: Elsevier BV
Date: 10-2023
EEG source localization in focal epilepsy: Where are we now?
Publisher: Wiley
Date: 17-10-2007
DOI: 10.1111/J.1528-1167.2007.01381.X
Abstract: Electroencephalographic source localization (ESL) by noninvasive means is an area of renewed interest in clinical epileptology. This has been driven by innovations in the computer-assisted modeling of dipolar and distributed sources for the investigation of focal epilepsy a process fueled by the ever-increasing computational power available to researchers for the analysis of scalp EEG recordings. However, demonstration of the validity and clinical utility of these mathematically derived source modeling techniques has struggled to keep pace. This review evaluates the current clinical "fitness' of ESL as applied to the focal epilepsies by examining some of the key studies performed in the field, with emphasis given to clinical work published in the last five years. In doing so, we discuss why ESL techniques have not made an impact on routine epilepsy practice, underlining some of the current problems and controversies in the field. We conclude by examining where ESL currently sits alongside magnetoencephalography and combined EEG-functional magnetic resonance imaging in the investigation of focal epilepsy.
Emulsion-coaxial electrospinning: designing novel architectures for sustained release of highly soluble low molecular weight drugs
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2JM31069D
EEG correlates of seizure freedom in genetic generalized epilepsies
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-11-2017
DOI: 10.1212/CPJ.0000000000000323
Abstract: We investigated the association between epileptiform EEG abnormalities and the preceding duration of seizure freedom in genetic generalized epilepsies (GGE). We analyzed 24-hour ambulatory EEG recordings of patients with GGE diagnosed and classified according to the International League Against Epilepsy criteria. We quantified epileptiform EEG abnormalities into density scores (total duration of epileptiform discharges per hour) and estimated the preceding seizure-free duration at the time of EEG recording based on the last self-reported seizure. We then employed regression analysis to quantitate the relationship between the duration of seizure freedom and EEG variables. We analyzed 6,923 epileptiform discharges from 105 patients with abnormal 24-hour EEGs. In the regression analysis exploring the crude associations, we found significant correlations between 6 EEG variables and the duration of seizure freedom indicating that shorter duration of seizure freedom was associated with higher spike densities and longer paroxysms. These associations were not affected by confounders such as syndrome, age at EEG, age at epilepsy onset, sex, duration of epilepsy, or number of antiepileptic drugs. Higher densities and longer durations of epileptiform discharges may be retrospectively associated with a shorter duration of self-reported seizure freedom. Hence, EEG can potentially be used as a biomarker of prognosis in GGE. These findings need to be validated in a prospective study in order to define EEG markers of future seizure freedom.
Multimodality image-guided epilepsy surgery
Publisher: Elsevier BV
Date: 11-2000
Validation of the concerns about epilepsy monitoring questionnaire (CAEMQ) - A measure of the concerns of epilepsy patients presenting for surgery
Publisher: Informa UK Limited
Date: 2000
Bifurcation analysis of two coupled Jansen-Rit neural mass models
Publisher: Public Library of Science (PLoS)
Date: 27-03-2018
Does the region of epileptogenicity influence the pattern of change in cortical excitability?
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.CLINPH.2014.05.029
Abstract: To investigate whether cortical excitability measures on transcranial magnetic stimulation (TMS) differed between groups of patients with different focal epilepsy syndromes. 85 Patients with focal epilepsy syndromes ided into temporal and extra-temporal lobe epilepsy were studied. The cohorts were further ided into drug naïve-new onset, refractory and seizure free groups. Motor threshold (MT) and paired pulse TMS at short (2, 5, 10, 15 ms) and long (100-300 ms) interstimulus intervals (ISIs) were measured. Results were compared to those of 20 controls. Cortical excitability was higher at 2 & 5 ms and 250, 300 ms ISIs (p<0.01) in focal epilepsy syndromes compared to controls however significant inter-hemispheric differences in MT and the same ISIs were only seen in the drug naïve state early at onset and were much more prominent in temporal lobe epilepsy. Disturbances in cortical excitability are more confined to the affected hemisphere in temporal lobe epilepsy but only early at onset in the drug naïve state. Group TMS studies show that cortical excitability measures are different in temporal lobe epilepsy and can be distinguished from other focal epilepsies early at onset in the drug naïve state. Further studies are needed to determine whether these results can be applied clinically as the utility of TMS in distinguishing between epilepsy syndromes at an in idual level remains to be determined.
Interictal spikes and epileptic seizures
Publisher: Oxford University Press (OUP)
Date: 17-02-2016
DOI: 10.1093/BRAIN/AWW019
Abstract: We report on a quantitative analysis of electrocorticography data from a study that acquired continuous ambulatory recordings in humans over extended periods of time. The objectives were to examine patterns of seizures and spontaneous interictal spikes, their relationship to each other, and the nature of periodic variation. The recorded data were originally acquired for the purpose of seizure prediction, and were subsequently analysed in further detail. A detection algorithm identified potential seizure activity and a template matched filter was used to locate spikes. Seizure events were confirmed manually and classified as either clinically correlated, electroencephalographically identical but not clinically correlated, or subclinical. We found that spike rate was significantly altered prior to seizure in 9 out of 15 subjects. Increased pre-ictal spike rate was linked to improved predictability however, spike rate was also shown to decrease before seizure (in 6 out of the 9 subjects). The probability distribution of spikes and seizures were notably similar, i.e. at times of high seizure likelihood the probability of epileptic spiking also increased. Both spikes and seizures showed clear evidence of circadian regulation and, for some subjects, there were also longer term patterns visible over weeks to months. Patterns of spike and seizure occurrence were highly subject-specific. The pre-ictal decrease in spike rate is not consistent with spikes promoting seizures. However, the fact that spikes and seizures demonstrate similar probability distributions suggests they are not wholly independent processes. It is possible spikes actively inhibit seizures, or that a decreased spike rate is a secondary symptom of the brain approaching seizure. If spike rate is modulated by common regulatory factors as seizures then spikes may be useful biomarkers of cortical excitability.
Intracranial EEG fluctuates over months after implanting electrodes in human brain
Publisher: IOP Publishing
Date: 09-2017
Psychosocial and neuropsychological outcomes in two high-functioning males 20 years after traumatic brain injury
Publisher: Informa UK Limited
Date: 07-1999
Electroencephalography in the Diagnosis of Genetic Generalized Epilepsy Syndromes
Publisher: Frontiers Media SA
Date: 25-09-2017
Arterial to end‐tidal carbon dioxide tension difference (CO2 gap) as a prognostic marker for adverse outcomes in emergency department patients presenting with suspected sepsis
Publisher: Wiley
Date: 13-05-2018
Abstract: The arterial to end-tidal carbon dioxide tension difference (CO Patients presenting to tertiary Australian ED with suspected sepsis (n = 215) underwent near-simultaneous end-tidal carbon dioxide and partial pressure of carbon dioxide measurements. We investigated the correlation of CO Among patients included in the analysis (n = 165), the CO In this pilot study of patients with suspected sepsis from non-respiratory causes, an increased CO
Novel single base pair COX III subunit deletion of mitochondrial DNA associated with rhabdomyolysis
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.JOCN.2010.06.001
Abstract: A high number of cytochrome c oxidase (COX)-negative muscle fibres (approximately 45%) without ragged red fibres was found in a 27-year-old male patient with a single unprovoked episode of severe rhabdomyolysis. There was no family history of neuromuscular disorder and sequencing revealed a novel COX III single base pair deletion (MT-CO3{NC_012920.1}:m.[9559delC]). The deletion creates a frame shift and downstream termination codon affecting the last 136 amino acids (MT-CO3{YP_003024032.1}:p.[Pro118GlnfsX124]). The heteroplasmic mutation load in muscle was approximately 58% and single COX-negative fibres harboured significantly greater levels of mutant mitochondrial DNA than COX-positive fibres.
Neuropsychological correlates of hippocampal and rhinal cortex volumes in patients with mesial temporal sclerosis
Publisher: Wiley
Date: 2003
DOI: 10.1002/HIPO.10128
Abstract: Considerable progress has been made toward understanding the function of the primate rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices. However, translating animal models to human memory has been limited by the technological problems associated with characterizing neural structures in vivo. Functional correlates of hippoc al and rhinal cortex volume changes were examined in a s le of 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS 33 left, 28 right). Patients were administered the Wechsler Adult Intelligence Scale (revised or third edition), the Wechsler Memory Scale (revised or third edition), and a spatial maze task. Neuropsychological data, together with rhinal cortex and hippoc al volumes, collected in our earlier study (O'Brien CE, Bowden SC, Whelan G, Cook MJ, unpublished observations), were analyzed using multiple regression. The only significant predictor of verbal memory function was the difference score between the volume of left hippoc us and the left PrC. Spatial maze scores were predicted by the bilateral sum of ErC volume. The difference score between the left hippoc us and left PrC volumes was the most powerful predictor of verbal episodic memory. Right hippoc al volume was not a significant predictor of nonverbal episodic memory. Verbal and nonverbal semantic memory were not significantly predicted by any combination of rhinal cortex structures. This quantitative study suggests a lateralized or material-specific memory function for the left hippoc us and left PrC, in contrast to the bilateral role of the ErC. The left hippoc us and left PrC appear to act on verbal memory function through an opposing relationship. Finally, differentiation between hippoc al and subhippoc al components in terms of episodic and semantic memory, respectively, could not be supported by the current data.
Olfactory acuity and identification: Dissociated abilities in psychosis and temporal lope epilepsy
Publisher: Elsevier BV
Date: 2000
Evaluation of Sca-1 and c-Kit as selective markers for muscle remodelling by nonhemopoietic bone marrow cells
Publisher: Oxford University Press (OUP)
Date: 15-02-2007
DOI: 10.1634/STEMCELLS.2006-0194
Abstract: Bone marrow (BM)-derived cells (BMCs) have demonstrated a myogenic tissue remodeling capacity. However, because the myoremodeling is limited to approximately 1%–3% of recipient muscle fibers in vivo, there is disagreement regarding the clinical relevance of BM for therapeutic application in myodegenerative conditions. This study sought to determine whether rare selectable cell surface markers (in particular, c-Kit) could be used to identify a BMC population with enhanced myoremodeling capacity. Dystrophic mdx muscle remodeling has been achieved using BMCs sorted by expression of stem cell antigen-1 (Sca-1). The inference that Sca-1 is also a selectable marker associated with myoremodeling capacity by muscle-derived cells prompted this study of relative myoremodeling contributions from BMCs (compared with muscle cells) on the basis of expression or absence of Sca-1. We show that myoremodeling activity does not differ in cells sorted solely on the basis of Sca-1 from either muscle or BM. In addition, further fractionation of BM to a more mesenchymal-like cell population with lineage markers and CD45 subsequently revealed a stronger selectability of myoremodeling capacity with c-Kit/Sca-1 (p & .005) than with Sca-1 alone. These results suggest that c-Kit may provide a useful selectable marker that facilitates selection of cells with an augmented myoremodeling capacity derived from BM and possibly from other nonmuscle tissues. In turn, this may provide a new methodology for rapid isolation of myoremodeling capacities from muscle and nonmuscle tissues. Disclosure of potential conflicts of interest is found at the end of this article.
Identifying seizure risk factors: A comparison of sleep, weather, and temporal features using a Bayesian forecast
Publisher: Wiley
Date: 30-12-2020
DOI: 10.1111/EPI.16785
Abstract: Most seizure forecasting algorithms have relied on features specific to electroencephalographic recordings. Environmental and physiological factors, such as weather and sleep, have long been suspected to affect brain activity and seizure occurrence but have not been fully explored as prior information for seizure forecasts in a patient‐specific analysis. The study aimed to quantify whether sleep, weather, and temporal factors (time of day, day of week, and lunar phase) can provide predictive prior probabilities that may be used to improve seizure forecasts. This study performed post hoc analysis on data from eight patients with a total of 12.2 years of continuous intracranial electroencephalographic recordings (average = 1.5 years, range = 1.0–2.1 years), originally collected in a prospective trial. Patients also had sleep scoring and location‐specific weather data. Histograms of future seizure likelihood were generated for each feature. The predictive utility of in idual features was measured using a Bayesian approach to combine different features into an overall forecast of seizure likelihood. Performance of different feature combinations was compared using the area under the receiver operating curve. Performance evaluation was pseudoprospective. For the eight patients studied, seizures could be predicted above chance accuracy using sleep (five patients), weather (two patients), and temporal features (six patients). Forecasts using combined features performed significantly better than chance in six patients. For four of these patients, combined forecasts outperformed any in idual feature. Environmental and physiological data, including sleep, weather, and temporal features, provide significant predictive information on upcoming seizures. Although forecasts did not perform as well as algorithms that use invasive intracranial electroencephalography, the results were significantly above chance. Complementary signal features derived from an in idual's historic seizure records may provide useful prior information to augment traditional seizure detection or forecasting algorithms. Importantly, many predictive features used in this study can be measured noninvasively.
Classification of Epileptic and Psychogenic Non-Epileptic Seizures Using Electroencephalography and Electrocardiography
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
The prevalence and demographic distribution of treated epilepsy: a community-based study in Tasmania, Australia
Publisher: Hindawi Limited
Date: 03-2012
DOI: 10.1111/J.1600-0404.2011.01499.X
Abstract: To estimate the prevalence and demographic distribution of treated epilepsy in a community-based population. We surveyed all residents in Tasmania, Australia, who were supplied at least one antiepileptic drug prescription between July 1, 2001 and June 30, 2002, recorded on the national prescription database. We adjusted for the effect of disease-related non-response bias by imputation methods. After three mail contacts, 54.0% (4072/7541) responded, with 1774 (43.6%) indicating treatment for epilepsy, representing 86.0% of the estimated total possible cases in Tasmania. The adjusted treated epilepsy prevalence was 4.36 per 1000 (95% CI 4.34, 4.39) lower in women (prevalence ratio 0.92 (95% CI 0.84, 1.00)) greater with increasing age (P < 0.001) similar in the three main geographic regions and similar with socioeconomic status of postcode of residence. Although our estimates are likely to be affected by access to health services, overall treated epilepsy prevalence of 4.4 per 1000 is similar to previous studies. Our finding of high elderly prevalence has been reported in a few recent studies in developed countries and has important clinical and public health implications in populations with similar aging demographics.
Teaching NeuroImage: open-ring imaging sign in a case of tumefactive cerebral demyelination
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2008
Surgical outcome in patients with epilepsy and dual pathology
Publisher: Oxford University Press (OUP)
Date: 05-1999
Abstract: High-resolution MRI can detect dual pathology (an extrahippoc al lesion plus hippoc al atrophy) in about 5-20% of patients with refractory partial epilepsy referred for surgical evaluation. We report the results of 41 surgical interventions in 38 adults (mean age 31 years, range 14-63 years) with dual pathology. Three patients had two operations. The mean postoperative follow-up was 37 months (range 12-180 months). The extrahippoc al lesions were cortical dysgenesis in 15, tumour in 10, contusion/infarct in eight and vascular malformation in five patients. The surgical approach aimed to remove what was considered to be the most epileptogenic lesion, and the 41 operations were classified into lesionectomy (removal of an extrahippoc al lesion) mesial temporal resection (removal of an atrophic hippoc us) and lesionectomy plus mesial temporal resection (removal of both the lesion and the atrophic hippoc us). Lesionectomy plus mesial temporal resection resulted in complete freedom from seizures in 11/15 (73%) patients, while only 2/10 (20%) patients who had mesial temporal resection alone and 2/16 (12.5%) who had a lesionectomy alone were seizure-free (P < 0.001). When classes I and II were considered together results improved to 86, 30 and 31%, respectively. Our findings indicate that in patients with dual pathology removal of both the lesion and the atrophic hippoc us is the best surgical approach and should be considered whenever possible.
Extending Communication for Patients with Disorders of Consciousness
Publisher: Wiley
Date: 28-08-2012
DOI: 10.1111/J.1552-6569.2012.00744.X
Abstract: The difficulty of distinguishing disorders of consciousness from certain disorders of communication leads to the possibility of false diagnosis. Our aim is to communicate with patients with disorders of consciousness through asking them to answer questions with "yes/no" by performing mental imagery tasks using functional magnetic resonance imaging (fMRI). A 1.5 T fMRI study with 5 patients and a control group is presented. Speech comprehension, mental imagery, and question-answer tests were performed. The imagery task of mental calculation produced equally distinct activation patterns when compared to navigation and motor imagery in controls. For controls, we could infer answers to questions based on imagery activations. Two patients produced activations in similar areas to controls for certain imagery tasks, however, no activations were observed for the question-answer task. The results from 2 patients provide independent support of similar work by others with 3 T fMRI, and demonstrate broader clinical utility for these tests at 1.5 T despite lower signal-to-noise ratio. Based on the control results, mental calculation adds a robust imagery task for use in future studies of this kind.
Characteristics of epileptiform discharge duration and interdischarge interval in genetic generalized epilepsies
Publisher: Frontiers Media SA
Date: 19-02-2018
Skull Defects in Finite Element Head Models for Source Reconstruction from Magnetoencephalography Signals
Publisher: Frontiers Media SA
Date: 07-04-2016
Seizure Detection Using Seizure Probability Estimation: Comparison of Features Used to Detect Seizures
Publisher: Springer Science and Business Media LLC
Date: 10-07-2009
DOI: 10.1007/S10439-009-9755-5
Abstract: This paper analyses seizure detection features and their combinations using a probability-based scalp EEG seizure detection framework developed by Marc Saab and Jean Gotman. Our method was evaluated on 525 h of data, including 88 seizures in 21 patients. The in idual performances of the three features used by Saab and Gotman were compared to six alternative features, and combinations of these nine features were analyzed in order to find a superior detector. On a testing set with the combination of their three features, Saab and Gotman reported a sensitivity of 0.78, a false positive rate of 0.86/h, and a median detection delay of 9.8 s. Based on 10-fold cross-validation the testing performance of our implementation of their method achieved a sensitivity of 0.79, a false positive rate of 0.62/h, and a median detection delay of 21.3 s. A detector based on an alternative combination of features achieved sensitivity of 0.81, a false positive rate of 0.60/h, and a median detection delay of 16.9 s. By including filtering techniques, it was possible to achieve performance levels similar to Saab and Gotman using our implementation of their method, although this involved increases in detection delays. Of the seizure detection measures investigated, relative average litude, relative power, relative derivative, and coefficent of variation of litude provided the best performing combinations. These better-performing features can be employed together to make robust and reliable seizure detectors.
Hippocampal deformation mapping in MRI negative PET positive temporal lobe epilepsy
Publisher: BMJ
Date: 10-10-2008
Abstract: To compare hippoc al surface structure, using large deformation high dimensional mapping (HDM-LD), in subjects with temporal lobe epilepsy (TLE) with (HS+ve) and without (HS-ve) hippoc al sclerosis. The study included 30 HS-ve subjects matched with 30 HS+ve subjects from the previously reported epilepsy patient cohort. To control for normal right-left asymmetries of hippoc al surface structure, subjects were regrouped based on laterality of onset of epileptic seizures and presence of HS. Gender ratio, age, duration of epilepsy and seizure frequency were calculated for each of the four groups. Final HDM-LD surface maps of the right and left TLE groups were compared to define differences in subregional hippoc al involvement within the groups. There were no significant differences in comparisons of the left TLE (left HS-ve compared with HS+ve) or right TLE (right HS-ve compared with HS+ve) groups with respect to age, duration of epilepsy or seizure severity scores. HDM-LD maps showed accentuated surface changes over the lateral hippoc al surface, in the region of the Sommer sector, in the hippoc i affected by HS. However, HS-ve hippoc i showed maximal surface changes in a different pattern, and did not involve the region of Sommer sector. We conclude that differences in segmental volume loss between the HS-ve and HS+ve groups are suggestive that the underlying pathophysiology of hippoc al changes in the two groups is different, and not related to chronic seizure duration or severity.
Epilepsyecosystem.org: crowd-sourcing reproducible seizure prediction with long-term human intracranial EEG
Publisher: Oxford University Press (OUP)
Date: 08-08-2018
DOI: 10.1093/BRAIN/AWY210
The assessment and treatment of concerns and anxiety in patients undergoing presurgical monitoring for epilepsy
Publisher: Wiley
Date: 11-1999
DOI: 10.1111/J.1528-1157.1999.TB02037.X
Abstract: This study investigated the impact of a treatment information package on patients being monitored for possible surgical treatment for temporal lobe epilepsy. One hundred patients were randomly assigned to either a high- or low-information preparation condition. Levels of anxiety were tested soon after admission by using the Hospital Anxiety and Depression Scale (HADS), The State-Trait Anxiety Inventory (STAI), and a newly devised questionnaire to assess specific concerns and anxieties of epilepsy patients presenting for monitoring and surgery, the Concerns About Epilepsy Monitoring Questionnaire (CAEMQ). Dispositional desire for information was assessed by the Miller Behavioural Style Scale (MBSS) to investigate whether coping disposition affected coping styles in the hospital setting. Patients assigned to the high-information condition were exposed to an intervention package, which included viewing a video depicting two separate interviews with patients who had undergone surgery as well as an information package, which described the various tests that the patient would undergo in the course of the monitoring procedure. Patients assigned to the low-information group were given information that the hospital provided to all patients in their care. All subjects were then retested on anxiety levels a few days later. Those in the high-information group showed a significant decrease in anxiety and depression levels compared with those in the low-information group. Within the main findings, an effect of dispositional style was found. Identification as either a monitor or blunter on the MBSS showed different coping strategies on arrival in hospital as measured by the CAEMQ, indicating that the level of information given to patients with epilepsy on arrival needs to be mediated by awareness of these two dispositional styles so that they obtain maximal benefit from the information to which patients with epilepsy are exposed.
Seizure severity and duration in the cortical stimulation model of experimental epilepsy in rats: a longitudinal study.
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.EPLEPSYRES.2010.01.010
Abstract: The aim of this study was to determine the current intensities necessary to elicit three levels of varying EEG and behavioural phenomena with electrical stimulation, and also to determine the consistency of the EEG and behavioural components of the triggered seizures over time. Electrical stimulation of the primary motor/somatosensory cortex was performed in 16 adult rats with multichannel microwire electrode arrays. Stimulation was delivered at a frequency of 60 Hz (1 ms pulse width), for 2 s duration, as biphasic rectangular pulses over four of the eight available electrode pairs. Current intensity thresholds for interruption of normal behaviour, epileptiform afterdischarge (EAD) longer than 5 s and motor seizures with Racine severity greater than 3 were not correlated to time post-surgery. The Racine threshold was shown to be negatively correlated to the EAD duration and Racine severity of seizures elicited in the following sessions. Seizures were reliably generated in rats through cortical stimulation with microwire electrode arrays and these seizures were not shown to be subject to any kindling type effects up to 53 days post-implantation. Both the electrographic duration and behavioural severity of stimulated seizures remained, on average, constant during this experimental period. Approximately one-third of stimulations did not cause observable motor seizures and of those that did result in seizures, forelimb clonus was the most common manifestation and the mean EAD duration was 18.5 s. No damage beyond that caused by surgical implantation of electrodes was observed in the histological analyses of stimulated and non-stimulated tissue. The consistency, duration and severity of seizures within this timeframe make this cortical stimulation model suitable for investigations into novel therapeutic interventions for epilepsy that require a known seizure focus.
Consistent topography and amplitude symmetry are more typical than morphology of epileptiform discharges in genetic generalized epilepsy
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.CLINPH.2015.08.019
Abstract: To provide a quantitative evaluation of typical electroencephalographic (EEG) abnormalities in genetic generalized epilepsy (GGE). We prospectively performed 24-h ambulatory EEG recordings in a cohort of patients with GGE. The diagnosis was established according to the International League Against Epilepsy criteria. Details of all epileptiform discharges across the 24-h time scale were entered into an electronic database. We carried out descriptive statistics to provide a quantitative breakdown of typical EEG abnormalities. A total of 6923 epileptiform discharges from 105 abnormal 24-h ambulatory EEGs were analyzed. 96% of discharges were symmetric in litude with fronto-central maximum topographically. Only 24% of the paroxysms had typical morphology while 43% were regular. Photoparoxysmal response, eye-closure sensitivity and hyperventilation-induced generalized paroxysms were less common in around 10%, whereas occipital intermittent rhythmic delta activity was very rare (2%). Our results indicate that generalized discharges with symmetric litude and fronto-central maxima are the most consistent findings in GGE, and other features are observed less frequently. Epileptiform discharges displaying highly consistent litude symmetry coupled with fronto-central topography should provoke consideration of GGE. Recognition of variations from typical abnormalities is important to avoid the risk of misdiagnosis and delayed diagnosis.
Exploring the tolerability of spatiotemporally complex electrical stimulation paradigms.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.EPLEPSYRES.2011.06.011
Abstract: A modified cortical stimulation model was used to investigate the effects of varying the synchronicity and periodicity of electrical stimuli delivered to multiple pairs of electrodes on seizure initiation. In this model, electrical stimulation of the motor cortex of rats, along four pairs of a microwire electrode array, results in an observable seizure with quantifiable electrographic duration and behavioural severity. Periodic stimuli had a constant inter-stimulus intervals across the two-second stimulus duration, whilst synchronous stimuli consisted of singular biphasic, bipolar pulses delivered to the four pairs of electrodes at precisely the same time for the entire two second stimulation period. In this way four combinations of stimulation were possible periodic/synchronous (P/S), periodic/asynchronous (P/As), aperiodic/synchronous (Ap/S) and aperiodic/asynchronous (Ap/As). All stimulation types were designed with equal pulse width, current intensity and mean frequency of stimulation (60 Hz), standardizing net charge transfer. It was expected that the periodicity of the stimulus would be the primary determinant of seizure initiation and therefore severity and electrographic duration. However, the results showed that significant differences in both severity and duration only occurred when the synchronicity was altered. For periodic stimuli, synchronous delivery increased median seizure duration from 5 s to 13 s and increased median Racine severity from 1 to 3. In the aperiodic case, synchronous stimulus delivery increased median duration from 5.5 s to 11s and resulted in seizures of median severity 3 vs. 0 in the asynchronous case. These findings may have implications for the design of future neurostimulation waveform designs as higher numbers of electrodes and stimulator output channels become available in next generation implants.
Continuous synthesis of artificial speech sounds from human cortical surface recordings during silent speech production
Publisher: IOP Publishing
Date: 27-07-2023
Abstract: Objective . Brain–computer interfaces can restore various forms of communication in paralyzed patients who have lost their ability to articulate intelligible speech. This study aimed to demonstrate the feasibility of closed-loop synthesis of artificial speech sounds from human cortical surface recordings during silent speech production. Approach . Ten participants with intractable epilepsy were temporarily implanted with intracranial electrode arrays over cortical surfaces. A decoding model that predicted audible outputs directly from patient-specific neural feature inputs was trained during overt word reading and immediately tested with overt, mimed and imagined word reading. Predicted outputs were later assessed objectively against corresponding voice recordings and subjectively through human perceptual judgments. Main results . Artificial speech sounds were successfully synthesized during overt and mimed utterances by two participants with some coverage of the precentral gyrus. About a third of these sounds were correctly identified by naïve listeners in two-alternative forced-choice tasks. A similar outcome could not be achieved during imagined utterances by any of the participants. However, neural feature contribution analyses suggested the presence of exploitable activation patterns during imagined speech in the postcentral gyrus and the superior temporal gyrus. In future work, a more comprehensive coverage of cortical surfaces, including posterior parts of the middle frontal gyrus and the inferior frontal gyrus, could improve synthesis performance during imagined speech. Significance. As the field of speech neuroprostheses is rapidly moving toward clinical trials, this study addressed important considerations about task instructions and brain coverage when conducting research on silent speech with non-target participants.
Correlation analysis of seizure detection features
Publisher: IEEE
Date: 12-2008
A forward-looking review of seizure prediction.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
Etiologies and characteristics of refractory status epilepticus cases in different areas of the world: Results from a global audit
Publisher: Wiley
Date: 29-08-2018
DOI: 10.1111/EPI.14496
Abstract: To describe the demographics, etiologies, types of status epilepticus (SE), and outcomes in people with refractory and super-refractory SE from around the world, we prospectively collected cases of refractory SE (RSE) treated with continuous intravenous anesthetic drugs in an intensive care unit setting through online questionnaires using "active surveillance." We collected information about 776 cases of RSE in 50 countries over 4 years. Control of SE was achieved in 74% of the cases. Neurologic outcomes were poor in 41% of patients, and 24% died. Good outcome was associated with younger age and a history of epilepsy. Etiology strongly influenced the outcome. Patients from Asia were younger, more frequently presented with convulsive SE, and were more frequently affected by infectious etiologies when compared with patients from Europe and the Americas. Despite these differences, outcomes were similar in all countries. Demographics of patients with RSE in a global audit are similar to those in prior single center series, providing evidence of generalizability of those studies. Important differences exist among patients with RSE from different regions of the world, but these do not seem to significantly influence patient outcomes.
Dysembryoplastic neuroepithelial tumour features in 16 patients
Publisher: Oxford University Press (OUP)
Date: 1994
Abstract: Dysembryoplastic neuroepithelial tumour (DNT) is a newly recognized brain mass lesion with distinctive pathological features and a favourable prognosis. We reviewed the clinical, electroencephalographic, neuroimaging and pathological features of 16 patients with DNT who underwent surgery only one patient did not have epilepsy. Mean age at seizure onset was 9.5 years (range: 1 week to 30 years) and surgery 17 years (range: 7 months to 37 years). The mean verbal IQ was 94.6 (range: 79-110) and performance IQ 105 (range: 79-130) (n = 10). The EEG was abnormal in all cases reviewed (n = 13): localized slow activity was seen in 12 and interictal spiking in 10 patients, being less extensive than or concordant with the lesion in three and more extensive than or distant to the lesion in seven. X-ray CT was normal in three out of 11 patients. Magnetic resonance imaging provided detailed anatomical information: the lesion was predominantly intracortical, although in six patients, there was also white matter involvement. The lesion involved the temporal lobe in all but one patient where it was in the cingulate gyrus. Of the temporal lobe cases, MRI showed that the lesion involved, or was in close proximity to, mesial temporal structures in 11 out of 14 patients. Other magnetic resonance features included: circumscribed hyperintensity on long TE/TR images (10 patients), hypointensity on short TR images (12 patients), and cyst formation (five patients). Calcification was seen on CT in four patients. Post surgical follow-up ranged from 8 to 30 months (mean 16.2 months): 12 patients are seizure free and two have a > 80% reduction in seizure frequency (n = 14). Histopathological characteristics included a heterogeneous composition in all cases, calcification (13 cases), dysplastic features (12 cases) and isolated foci of subpial spread (five cases). The presence of occasional mitoses in 12 cases and immunoreactivity to the proliferating cell nuclear antigen in six cases indicate that these lesions have cellular proliferative activity and that there may be a need to follow these patients postoperatively.
SPINAL DISEASE: NEOPLASTIC, DEGENERATIVE, AND INFECTIVE SPINAL CORD DISEASES AND SPINAL CORD COMPRESSION
Publisher: Elsevier
Date: 1999
Therapeutic DNA delivery to skeletal muscle
Publisher: Bentham Science Publishers Ltd.
Date: 05-2006
Quantitative MRI in outpatient childhood epilepsy
Publisher: Wiley
Date: 12-1997
DOI: 10.1111/J.1528-1157.1997.TB00066.X
Abstract: In adult studies, MRI volumetrics is a proven technique in presurgical assessment of epilepsy. Hippoc al volume loss is maximal in the syndrome of mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a pediatric outpatient epilepsy population (b) to determine the relationship of hippoc al asymmetry (HA) to epileptic syndromes and risk factors. Two neurologists classified the epileptic syndrome in 79 pediatric outpatients, according to the International Classification of Epilepsies and Epileptic Syndromes (ILAE). Hippoc al volumetrics were performed in all patients. HA was defined according to adult control values. Inter-rater variability on measurement of HA was very small (Correlation of test retest of 0.97 on 17 children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%) potentially epileptogenic lesions (other than HA) were identified (cerebral dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in 15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized symptomatic epilepsy. Analysis confined to <13 years also showed HA was not specific for epileptic syndrome. There was no significant association of febrile convulsions (13%) with HA or temporal lobe epilepsy. There is a high incidence of HA in childhood epilepsy. HA was not confined to clinically defined temporal lobe epilepsy. The poor correlation of epileptic syndrome to quantitative MRI findings may be due to the inadequacies of epilepsy classification in the younger child, with the clinical semiology providing misleading localizing information. Normative childhood data for hippoc al volumes and symmetry is needed.
Ring and peg electrodes for minimally-Invasive and long-term sub-scalp EEG recordings
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.EPLEPSYRES.2017.06.003
Abstract: Minimally-invasive approaches are needed for long-term reliable Electroencephalography (EEG) recordings to assist with epilepsy diagnosis, investigation and more naturalistic monitoring. This study compared three methods for long-term implantation of sub-scalp EEG electrodes. Three types of electrodes (disk, ring, and peg) were fabricated from biocompatible materials and implanted under the scalp in five ambulatory ewes for 3months. Disk electrodes were inserted into sub-pericranial pockets. Ring electrodes were tunneled under the scalp. Peg electrodes were inserted into the skull, close to the dura. EEG was continuously monitored wirelessly. High resolution CT imaging, histopathology, and impedance measurements were used to assess the status of the electrodes at the end of the study. EEG litude was larger in the peg compared with the disk and ring electrodes (p<0.05). Similarly, chewing artifacts were lower in the peg electrodes (p<0.05). Electrode impedance increased after long-term implantation particularly for those within the bone (p<0.01). Micro-CT scans indicated that all electrodes stayed within the sub-scalp layers. All pegs remained within the burr holes as implanted with no evidence of extrusion. Eight of 10 disks partially eroded into the bone by 1.0mm from the surface of the skull. The ring arrays remained within the sub-scalp layers close to implantation site. Histology revealed that the electrodes were encapsulated in a thin fibrous tissue adjacent to the pericranium. Overlying this was a loose connective layer and scalp. Erosion into the bone occurred under the rim of the sub-pericranial disk electrodes. The results indicate that the peg electrodes provided high quality EEG, mechanical stability, and lower chewing artifact. Whereas, ring electrode arrays tunneled under the scalp enable minimal surgical techniques to be used for implantation and removal.
Australia's seizure divide — indigenous versus non-indigenous seizure hospitalization
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.YEBEH.2013.09.042
Abstract: Indigenous Australians suffer the highest mortality and morbidity rates of any ethnic minority in the developed world. To determine if the health outcome gulf between indigenous and non-indigenous Australians also applied to seizures, we conducted a retrospective analysis of seizure hospitalization (1998-2004) based on ethnicity (indigenous (I) and non-indigenous (NI)) for four Australian jurisdictions - Northern Territory (NT), Queensland (Qld), South Australia (SA), and Western Australia (WA). Total admissions were converted to age-standardized rates (ASR) and I/NI ASR ratios (I/NIRR) and compared across multiple variables. The summed admission (combined jurisdictions over six years) was 71,185 (I=11,593 and NI=59,592). Seizure hospitalization rate was always higher in the indigenous population (six-year I/NIRR - NT=5.6, Qld=4.0, SA=6.4, and WA=10.9 combined jurisdictions=5.6). Disparity was greatest for ages 40-64years (13.8) and 15-39years (7.0) and for indigenous males (7.4). As socioeconomic status rose, non-indigenous admission rates fell (ASR=1.7 to 1.1), yet indigenous admission rates rose (ASR=7.9 to 14.0). Indigenous emergency to elective admission ratios were higher (I=27 and NI=8), as were readmissions (1.5-2 fold), self-discharge separations (I=9.4% and NI=1.4%), bed days (I/NIRR=5.1), and admissions with an additional diagnosis (I/NIRR=3.3) or procedure (I/NIRR=3.4). Indigenous Australians maintained disproportionately high rates of emergency seizure hospitalization from 1998 to 2004, the combined jurisdiction rate was more than five times the mean non-indigenous rate. Indigenous males aged 15-64years were overrepresented. Indigenous patients had lengthier admissions but higher self-discharge and readmission rates. The socioeconomic data raise the concern that social disadvantage restricts access to hospital-based seizure care for indigenous patients.
PATIENT-SPECIFIC NEURAL MASS MODELING - STOCHASTIC AND DETERMINISTIC METHODS
Publisher: WORLD SCIENTIFIC
Date: 08-09-2013
Evaluation of the Biocompatibility of Polypyrrole Implanted Subdurally in GAERS.
Publisher: Wiley
Date: 05-12-2017
Abstract: This blinded controlled prospective randomized study investigates the biocompatibility of polypyrrole (PPy) polymer that will be used for intracranial triggered release of anti-epileptic drugs (AEDs). Three by three millimeters PPy are implanted subdurally in six adult female genetic absence epilepsy rats from Strasbourg. Each rat has a polymer implanted on one side of the cortex and a sham craniotomy performed on the other side. After a period of seven weeks, rats are euthanized and parallel series of coronal sections are cut throughout the implant site. Four series of 15 sections are histological (hematoxylin and eosin) and immunohistochemically (neuron-specific nuclear protein, glial fibrillary acidic protein, and anti-CD68 antibody) stained and evaluated by three investigators. The results show that implanted PPy mats do not induce obvious inflammation, trauma, gliosis, and neuronal toxicity. Therefore the authors conclude the PPy used offer good histocompatibility with central nervous system cells and that PPy sheets can be used as intracranial, AED delivery implant.
'MRI-negative PET-positive' temporal lobe epilepsy (TLE) and mesial TLE differ with quantitative MRI and PET: a case control study
Publisher: Springer Science and Business Media LLC
Date: 24-06-2007
Equivalence of a measurement model of cognitive abilities in U.S. standardization and Australian neuroscience samples
Publisher: SAGE Publications
Date: 06-2008
Abstract: A psychological measurement model provides an explicit definition of (a) the theoretical and (b) the numerical relationships between observed scores and the latent variables that underlie the observed scores. Examination of the metric invariance of a measurement model involves testing the hypothesis that all components of the model relating observed scores to latent variables are equal across groups. The assumption of metric invariance is necessary for simple interpretation of scores. Establishing metric invariance also has implications for interpretation of convergent and ergent validity and patterns of deficit or disability. In this study the equivalence of the measurement model derived from the U.S. Wechsler Adult Intelligence Scale–III standardization s le was compared with a heterogeneous neurosciences s le in Australia. A pattern of strict metric invariance was observed across s les. These results provide evidence of the generality of the model underlying measurement of cognitive abilities.
ON THE MIDWAY TO EPILEPSY: IS CORTICAL EXCITABILITY NORMAL IN PATIENTS WITH ISOLATED SEIZURES?
Publisher: World Scientific Pub Co Pte Lt
Date: 29-01-2014
DOI: 10.1142/S0129065714300022
Abstract: Paired pulse transcranial magnetic stimulation was used to investigate differences in cortical excitability between patients with isolated (unrecurrent, unprovoked) seizures and those with epilepsy. Compared to controls, cortical excitability was higher in the isolated seizure group at 250–300 ms. Compared to epilepsy, cortical excitability was lower in patients with isolated seizures also at 250 and 300 ms. Lowered seizure threshold caused by disturbances within inhibitory circuits is present in patients who experience a seizure even if no further seizures occur.
Degree of hippocampal atrophy is not related to a history of febrile seizures in patients with proved hippocampal sclerosis
Publisher: BMJ
Date: 12-2000
Abstract: To examine the degree of hippoc al atrophy in patients with temporal lobe epilepsy and proved hippoc al sclerosis to determine whether or not patients with febrile seizures have more severe hippoc al atrophy. To determine whether or not there is a relation between age of seizure onset, duration of temporal lobe epilepsy, or seizure frequency, and severity of hippoc al atrophy. Hippoc al volumes were measured from volumetrically acquired MR images in 77 consecutive surgical patients with temporal lobe epilepsy (37 febrile seizures (FS)+, 40 FS-) with proved hippoc al sclerosis, and compared with 98 controls. Ipsilateral and contralateral hippoc al volumes were not significantly different between the FS+ and FS- groups. There was no difference in the age of onset of habitual seizures, duration of epilepsy, or age at the time of surgery, between these groups. No clinically significant correlations were found between hippoc al volumes and age of onset of first non-febrile seizure, duration of temporal lobe epilepsy, or complex partial and secondarily generalised seizure frequency, in patients with and without febrile seizures. Although febrile seizures was associated with hippoc al sclerosis in 48% of patients in this surgical series, the degree of MRI determined hippoc al atrophy was not related to a history of such seizures. The results do not support the view that febrile seizures cause more severe hippoc al sclerosis and are consistent with the hypothesis that hippoc al sclerosis is a pre-existing abnormality.
Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.JOCN.2004.05.003
Abstract: To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study. A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy with epilepsy not taking AEDs taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes. 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (16.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1%, [Formula: see text] ). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (1,975 vs. 1,128 mg, P or= 1,100 mg was 30.2% vs. 3.2% with doses <1,100 mg (P <0.01). There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy.
A taxonomy of seizure dynamotypes
Publisher: Cold Spring Harbor Laboratory
Date: 09-02-2020
DOI: 10.1101/2020.02.08.940072
Abstract: Seizures are a disruption of normal brain activity present across a vast range of species, diseases, and conditions. Here we introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory, and applied it to the analysis of EEG data. The “dynamotype” of a seizure is the part of its dynamic composition that defines its observable characteristics, including how it starts, evolves and terminates. Analyzing over 2000 focal-onset seizures recorded from 7 epilepsy centers on five continents, we find evidence of all 16 dynamotypes predicted in TSD. We demonstrate that patients’ dynamotypes evolve during their lifetime and display complex but systematic variations including hierarchy (certain dynamotypes are more common), non-bijectivity (a patient may display multiple dynamotypes) and pairing preference (multiple dynamotypes may occur during one seizure). TSD not only provides a way to stratify patients in complement to present practical classifications but also guides biophysically based mechanistic approaches and provides a language to describe the most critical features of seizure dynamics. Taxonomy of Seizure Dynamics (TSD) provides a rigorous method for classifying and quantifying seizures and a principled framework for understanding seizure initiation and propagation.
Corrigendum to “Preliminary results of the Global Audit of Treatment of Refractory Status Epilepticus” [Epilepsy Behav. 49C (2015) 318–324]
Publisher: Elsevier BV
Date: 11-2015
A community survey of cardiovascular risk factors in an urban population in Botswana exploring potential for telemedicine
Publisher: Elsevier BV
Date: 09-2014
Development of drug-loaded polymer microcapsules for treatment of epilepsy
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7BM00623C
Abstract: Fibre- and sphere-based microcapsules have been developed, exhibiting controllable uniform morphologies, predictable drug release profiles, and neuro-cytocompatibility.
Seizure occurrence is linked to multiday cycles in diverse physiological signals
Publisher: Wiley
Date: 20-04-2023
DOI: 10.1111/EPI.17607
Abstract: The factors that influence seizure timing are poorly understood, and seizure unpredictability remains a major cause of disability. Work in chronobiology has shown that cyclical physiological phenomena are ubiquitous, with daily and multiday cycles evident in immune, endocrine, metabolic, neurological, and cardiovascular function. Additionally, work with chronic brain recordings has identified that seizure risk is linked to daily and multiday cycles in brain activity. Here, we provide the first characterization of the relationships between the cyclical modulation of a erse set of physiological signals, brain activity, and seizure timing. In this cohort study, 14 subjects underwent chronic ambulatory monitoring with a multimodal wrist‐worn sensor (recording heart rate, accelerometry, electrodermal activity, and temperature) and an implanted responsive neurostimulation system (recording interictal epileptiform abnormalities and electrographic seizures). Wavelet and filter–Hilbert spectral analyses characterized circadian and multiday cycles in brain and wearable recordings. Circular statistics assessed electrographic seizure timing and cycles in physiology. Ten subjects met inclusion criteria. The mean recording duration was 232 days. Seven subjects had reliable electroencephalographic seizure detections (mean = 76 seizures). Multiday cycles were present in all wearable device signals across all subjects. Seizure timing was phase locked to multiday cycles in five (temperature), four (heart rate, phasic electrodermal activity), and three (accelerometry, heart rate variability, tonic electrodermal activity) subjects. Notably, after regression of behavioral covariates from heart rate, six of seven subjects had seizure phase locking to the residual heart rate signal. Seizure timing is associated with daily and multiday cycles in multiple physiological processes. Chronic multimodal wearable device recordings can situate rare paroxysmal events, like seizures, within a broader chronobiology context of the in idual. Wearable devices may advance the understanding of factors that influence seizure risk and enable personalized time‐varying approaches to epilepsy care.
Tolerability, safety, and side effects of levetiracetam versus phenytoin in intravenous and total prophylactic regimen among craniotomy patients: A prospective randomized study
Publisher: Wiley
Date: 27-06-2012
DOI: 10.1111/J.1528-1167.2012.03563.X
Abstract: Practical choice in parenteral antiepileptic drugs (AEDs) remains limited despite formulation of newer intravenous agents and requirements of special patient groups. This study aims to compare the tolerability, safety, and side effect profiles of levetiracetam (LEV) against the standard agent phenytoin (PHT) when given intravenously and in total regimen for seizure prophylaxis in a neurosurgical setting. This prospective, randomized, single-center study with appropriate blinding comprised evaluation pertaining to intravenous use 3 days following craniotomy and at discharge, and to total intravenous-plus-oral AED regimen at 90 days. Primary tolerability end points were discontinuation because of side effect and first side effect. Safety combined end point was major side effect or seizure. Seizure occurrence and side effect profiles were compared as secondary outcomes. Of 81 patients randomized, 74 (36 LEV, 38 PHT) received parenteral AEDs. No significant difference attributable to intravenous use was found between LEV and PHT in discontinuation because of side effect (LEV 1/36, PHT 2/38, p = 1.00) or number of patients with side effect (LEV 1/36, PHT 4/38, p = 0.36). No significant difference was found between LEV and PHT total intravenous-plus-oral regimen in discontinuation because of side effect (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.21-2.92, p = 0.72) or number of patients with side effect (HR 1.51, 95% CI 0.77-2.98, p = 0.22). More patients assigned PHT reached the undesirable clinical end point for safety of major side effect or seizure (HR 0.09, 95% CI 0.01-0.70, p = 0.002). Seizures occurred only in patients assigned PHT (n = 6, p = 0.01). Although not significant, trends were observed for major side effect in more patients assigned PHT (p = 0.08) and mild side effect in more assigned LEV (p = 0.09). Both LEV and PHT are well-tolerated perioperatively in parenteral preparation, and in total intravenous-plus-oral prophylactic regimen. Comparative safety and differing side effect profile of intravenous LEV supports use as an alternative to intravenous PHT.
A simple and versatile method for microencapsulation of anti-epileptic drugs for focal therapy of epilepsy
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5TB00675A
Abstract: Nearly 30% of epilepsy cases cannot be adequately controlled with current medical treatments.
Statistical Performance Analysis of Data-Driven Neural Models
Publisher: World Scientific Pub Co Pte Lt
Date: 08-11-2017
DOI: 10.1142/S0129065716500453
Abstract: Data-driven model-based analysis of electrophysiological data is an emerging technique for understanding the mechanisms of seizures. Model-based analysis enables tracking of hidden brain states that are represented by the dynamics of neural mass models. Neural mass models describe the mean firing rates and mean membrane potentials of populations of neurons. Various neural mass models exist with different levels of complexity and realism. An ideal data-driven model-based analysis framework will incorporate the most realistic model possible, enabling accurate imaging of the physiological variables. However, models must be sufficiently parsimonious to enable tracking of important variables using data. This paper provides tools to inform the realism versus parsimony trade-off, the Bayesian Cramer-Rao (lower) Bound (BCRB). We demonstrate how the BCRB can be used to assess the feasibility of using various popular neural mass models to track epilepsy-related dynamics via stochastic filtering methods. A series of simulations show how optimal state estimates relate to measurement noise, model error and initial state uncertainty. We also demonstrate that state estimation accuracy will vary between seizure-like and normal rhythms. The performance of the extended Kalman filter (EKF) is assessed against the BCRB. This work lays a foundation for assessing feasibility of model-based analysis. We discuss how the framework can be used to design experiments to better understand epilepsy.
Volumetric analysis of a specific language region - The planum temporale
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.JOCN.2005.03.026
Abstract: Planum temporale volumes were determined for 42 control children (ages 4.2-15.7 years) using magnetic resonance imaging. The mean left planum temporale volume was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3 (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co-variance (ANCOVA) showed that the absolute and proportional planum temporale volumes were not significantly associated with age or gender. We also demonstrated a reproducible method for planum temporale volume measurement by acquiring images in the coronal plane and then visualising the sagittal plane to improve accuracy for the posterior border.
Neuropsychological Aspects of Temporal-Lobe Epilepsy: Seeking Evidence-Based Practice
Publisher: Springer International Publishing
Date: 10-09-2015
MRI-negative PET-positive temporal lobe epilepsy: A distinct surgically remediable syndrome
Publisher: Oxford University Press (OUP)
Date: 28-07-2004
DOI: 10.1093/BRAIN/AWH257
Serial MRI in multiple sclerosis: a prospective pilot study of lesion load, whole brain volume and thalamic atrophy
Publisher: Elsevier BV
Date: 02-2004
DOI: 10.1016/S0967-5868(03)00145-0
Abstract: Using serial magnetic resonance imaging (MRI), we investigated the relationship between diffuse cerebral atrophy, T1 and T2 lesion volumes, mean thalamic volumes and clinical progression in patients with established multiple sclerosis (MS). Eleven patients were included in this prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, and T2 hyperintense lesion volumes at baseline and at up to 3 years follow-up were assessed on MRI brain scans. As a putative measure of cerebral atrophy mean thalamic volumes were also obtained. The outcome measures were the MRI parameters and disability on Kurtzke's expanded disability status scale (EDSS). Of the 11 patients 6 worsened clinically as measured by an increase of 0.5 or more on the EDSS. Cerebral atrophy occurred in 91% of patients and was independent of changes in lesion volumes and was not associated with disease progression as determined by the EDSS.
HIPPOCAMPAL VOLUMETRIC AND MORPHOMETRIC STUDIES IN FRONTAL AND TEMPORAL-LOBE EPILEPSY
Publisher: Oxford University Press (OUP)
Date: 1992
Abstract: The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different imaging techniques have been utilized to detect this with varying success. We describe the clinical application of magnetic resonance imaging (MRI) using a three-dimensional volume technique which allows total hippoc al volume to be measured and symmetry evaluated. Hippoc al surface area was calculated in sequential 1.5 mm thick contiguous images, using a GE IC workstation. Total volumes and surface areas were calculated. The cross-sectional surface area at 1.5 mm intervals was displayed graphically, permitting morphometric analysis of the hippoc us throughout its length. Focal atrophy within any part of the hippoc al formation (HF) and its extent could thus be assessed. Patients with well-lateralized temporal lobe epilepsy (TLE) (n = 20) and well-defined frontal lobe epilepsy (FLE) (n = 20) were studied, and volumes compared with normal values derived from 10 neurologically normal controls. Asymmetric hippoc al volume loss was demonstrated in all 20 patients with clinically typed TLE, but not in normal controls or patients with FLE. Volume loss distribution was anterior in 12 patients, posterior in one patient and widespread in seven patients. Secondarily generalized seizures were strongly associated with widespread loss. This method of surface area and volumetric analysis of the hippoc us in TLE can demonstrate asymmetry and focal involvement, and help distinguish between hippoc al and frontal pathologies.
Recurrent unresponsive episodes and seizures
Publisher: AMPCo
Date: 11-2011
DOI: 10.5694/MJA11.11260
Abstract: Careful history-taking is essential when evaluating patients with suspected epileptic seizures. It should focus on ascertaining whether the episodes are seizures or a seizure mimic such as syncope. Recurrent unresponsive episodes associated with seizures may indicate a diagnosis of focal epilepsy or complex partial epilepsy. Adults with a clinical diagnosis of a focal seizure disorder require investigation with electroencephalography and magnetic resonance imaging. The goal of treatment should be to achieve a life free of seizures, with minimum adverse effects from anticonvulsant medication. The choice of medication should be in idualised to a patient's seizure characteristics, circumstances and preferences. Dose adjustments should be made according to clinical response (seizure frequency and adverse effects), rather than on serum drug concentrations alone. Lifestyle advice, such as advice about driving restrictions, is important for the safety of the patient and others. All anticonvulsants are potentially teratogenic. Poorly controlled epilepsy in pregnancy imparts significant risks to the mother and baby, which need to be weighed against the risks of teratogenicity. The risk of major congenital malformations is highest with valproate, particularly in high doses.
The utility of ambulatory electroencephalography in routine clinical practice: A critical review
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.EPLEPSYRES.2013.02.004
Abstract: Over the last four decades, ambulatory electroencephalography (EEG) has evolved to be a useful tool in the diagnosis of epilepsy and certain nonepileptic paroxysmal disorders. Most of the initial technological drawbacks of ambulatory EEG have been circumvented by incorporating digital and computer technology. It appears superior to routine EEG in capturing interictal abnormalities particularly in relation to natural sleep, circadian variations and the patient's typical daily lifestyle. The role of ambulatory EEG in studying seizures and nonepileptic paroxysmal events remains to be defined by targeted research. It perhaps is an underutilized tool and more research is needed to expand the horizon of ambulatory EEG applications in clinical practice.
ILAE-defined epilepsy syndromes in children: Correlation with quantitative MRI
Publisher: Wiley
Date: 12-1998
DOI: 10.1111/J.1528-1157.1998.TB01335.X
Abstract: The role of quantitative magnetic resonance imaging (MRI) in evaluation of childhood epilepsy remains poorly defined, with minimal published data. Previous work from our center questioned the specificity of hippoc al asymmetry (HA) in an outpatient group whose epilepsy was defined by using clinical and interictal data only. By using childhood volunteer controls and defining epilepsy syndromes using video-EEG monitoring, we readdressed the utility of HA in differentiating mesial temporal lobe epilepsy (MTLE) from other partial and generalized epileptic syndromes in children. Seventy children were enrolled entry criteria were age younger than 18 years with predominant seizure type recorded on video-EEG telemetry with volumetric MRI in all cases. Thirty healthy child volunteers had volumetric MRI. Epilepsy syndrome classification was according to ILAE. Control data revealed symmetric hippoc i, mean smaller/larger ratio of 0.96 (0.95-0.97, 95% CI) with no gender or right/left predominance. Overall 23% of patients had significant HA. Mean hippoc al ratio for MTLE was 0.78 (95% CI, 0.70-0.86), significantly lower than controls and from all other epilepsy syndromes. HA was highly specific (85%) to the syndrome of MTLE. Other potential epileptogenic lesions were found in 27 (39%) patients, lowest yield in frontal and mesial temporal syndromes. Dual pathology was present in 10% of patients. There was no significant association between HA and risk factors. In this study, we found that HA in children with a well-defined epilepsy syndrome is highly sensitive and specific for MTLE. Whether this will correlate with surgical outcome, as in adults, is the subject of ongoing study.
MRI and epilepsy surgery
Publisher: Elsevier BV
Date: 10-1996
An integrative review of the benefits of self-management interventions for adults with epilepsy
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.YEBEH.2015.01.026
Abstract: The life-limiting effects of epilepsy are well documented in the literature, where the management of epilepsy and seizure control relies heavily on the self-management abilities of the in idual. The psychosocial impact of epilepsy on the person and their family is profound and has been studied extensively. Interventions such as educational programs and lifestyle management education to improve self-mastery and quality of life in people with epilepsy are not necessarily integrated in standard care practices. The aim of this integrative review was to systematically identify and appraise research that reported findings related to self-management interventions for adults with epilepsy. A search of bibliographic databases was conducted, and a total of n=14 articles were included in this review. The main finding was that self-management education for adults with epilepsy shows promise to improving knowledge and self-confidence in managing one's own condition including the management of the psychosocial stressors, improvement in seizure control, and enhancement of quality of life. Self-management interventions were delivered in erse formats, and the inclusion of this type of intervention should be part of the comprehensive care for people living with epilepsy.
Persistent anosmia and olfactory bulb atrophy after mulga (Pseudechis australis) snakebite
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.JOCN.2015.12.019
Abstract: Loss of sense of smell is an intriguing yet under-recognised complication of snakebite. We report olfactory function testing and neuroimaging of the olfactory bulbs in a 30-year-old man with anosmia persisting for more than 1year after mulga (Pseudechis australis) snakebite. This problem was first noted by the patient 1week after being definitely bitten in Queensland, Australia. He had then presented to a regional hospital where his envenomation was considered mild enough to not warrant antivenom administration. A week later the patient noted a reduction of sense of smell, which progressed to complete inability to smell over the ensuing weeks. On clinical review the patient's neurologic and rhinologic examination did not reveal any structural cause for anosmia. Formal olfactory testing was performed using ''sniffin' sticks" and the patient scored 17 on this test, indicating severe hyposmia (functional anosmia 30.3 for men aged 16-35years). MRI of the brain showed no abnormalities. The olfactory bulb volumes were then measured on a volumetric T2-weighted MRI that demonstrated significantly reduced volume of both bulbs, with the right 34.86mm(3) and left 36.25mm(3) (normal volume ⩾58mm(3), 10th centile). The current patient represents a rare instance of a definite, untreated, elapid (mulga snake) envenomation with an intriguing disjunction between the mildness of the systemic features and the severity of the olfactory lesion. It is also unclear if early antivenom use attenuates this condition, and due to the delayed manifestation of the symptoms, awareness of this phenomenon may be lacking amongst physicians.
Managing drug-resistant epilepsy: Challenges and solutions
Publisher: Informa UK Limited
Date: 10-2016
DOI: 10.2147/NDT.S84852
Epileptic Seizure Prediction Using Big Data and Deep Learning: Toward a Mobile System
Publisher: Elsevier BV
Date: 2018
The Tasmanian Epilepsy Register - A community based cohort
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000112859
Abstract: i Background/Aims: /i Centralized prescription databases may provide an efficient mechanism for recruitment of community-treated disease. i Methods: /i The Australian federal government agency, the Health Insurance Commission (HIC), invited patients to participate in the Tasmanian Epilepsy Register (TER). Eligible patients included those who received at least one anticonvulsant above a ‘reportable’ price threshold between July 1, 2001 and June 30, 2002. Patients were asked to disclose their medical indication for anticonvulsant treatment with additional demographic and prescription information obtained from the HIC. i Results: /i 7,541 were eligible for recruitment. After two mail invitations over 6 months, 3,375 (46.6%) had responded, but TER enrollment amongst those indicating treatment for epilepsy was 1,180 (78.3%). TER participants were more likely to obtain their prescriptions exclusively from their general practitioner (70.9%) or from combined sources (19.1%) rather than from pediatrician (4.2%), neurologist (1.4%) or general physician (1.0%) sources. Patients were more likely to respond with increasing age (linear trend p 0.001), when from a higher socioeconomic area (linear trend p 0.001), or if their prescription was obtained from a neurologist (p 0.001). i Conclusion: /i The national Australian prescription database represents community-treated epilepsy and provides an effective and efficient method for patient recruitment for clinical epidemiological research.
Epileptic Seizures and the EEG
Publisher: CRC Press
Date: 19-04-2010
DOI: 10.1201/B10459
Domino-like transient dynamics at seizure onset in epilepsy
Publisher: Public Library of Science (PLoS)
Date: 28-09-2020
Model-based estimation of intra-cortical connectivity using electrophysiological data
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.NEUROIMAGE.2015.06.048
Abstract: This paper provides a new method for model-based estimation of intra-cortical connectivity from electrophysiological measurements. A novel closed-form solution for the connectivity function of the Amari neural field equations is derived as a function of electrophysiological observations. The resultant intra-cortical connectivity estimate is driven from experimental data, but constrained by the mesoscopic neurodynamics that are encoded in the computational model. A demonstration is provided to show how the method can be used to image physiological mechanisms that govern cortical dynamics, which are normally hidden in clinical data from epilepsy patients. Accurate estimation performance is demonstrated using synthetic data. Following the computational testing, results from patient data are obtained that indicate a dominant increase in surround inhibition prior to seizure onset that subsides in the cases when the seizures spread.
Response to photic stimulation as a measure of cortical excitability in epilepsy patients
Publisher: Cold Spring Harbor Laboratory
Date: 24-04-2023
DOI: 10.1101/2023.04.23.537976
Abstract: Studying states and state transitions in the brain is challenging due to the nonlinear, complex dynamics present. In this research, we analyse the brain’s response to non-invasive perturbations. Perturbation techniques offer a powerful method for studying complex dynamics [1], though their translation to human brain data is under-explored. This method involves applying small inputs, in this case via photic stimulation, to a system and measuring its response. Sensitivity to perturbations can forewarn a state transition [1], therefore biomarkers of the brain’s perturbation response or ‘cortical excitability’ could be used to indicate seizure transitions [2 3 4]. However, perturbing the brain often involves invasive intracranial surgeries [5] or expensive equipment as in transcranial magnetic stimulation (TMS) which is only accessible to a minority of patient groups [6 7], or animal model studies [8]. Photic stimulation is a widely used diagnostic technique in epilepsy [9] that can be used as a non-invasive perturbation paradigm to probe brain dynamics during routine electroencephalography (EEG) studies in humans. This involves changing the frequency of strobing light, sometimes triggering a photo-paroxysmal response (PPR), which is an electrographic event that can be studied as a state transition to a seizure state. We investigate alterations in the response to these perturbations in patients with genetic generalised epilepsy (GGE), with (n=10) and without (n=10) PPR, and patients with psychogenic non-epileptic seizures (PNES n=10), compared to resting controls (n=10). Metrics of EEG time-series data were evaluated as biomarkers of the perturbation response including variance, autocorrelation, and phase-based synchrony measures. We observed considerable differences in all group biomarker distributions during stimulation compared to controls. In particular, variance and autocorrelation demonstrated greater changes in epochs close to PPR transitions compared to earlier stimulation epochs. Comparison of PPR and spontaneous seizure morphology found them indistinguishable, suggesting PPR is a valid proxy for seizure dynamics. Also, as expected, posterior channels demonstrated the greatest change in synchrony measures, possibly reflecting underlying PPR pathophysiology mechanisms [9]. We clearly demonstrate observable changes at a group level in cortical excitability in epilepsy patients as a response to perturbation in EEG data. Our work re-frames photic stimulation as a non-invasive perturbation paradigm capable of inducing measurable changes to brain dynamics.
Degree of left hippocampal atrophy correlates with severity of neuropsychological deficits
Publisher: Elsevier BV
Date: 06-1997
DOI: 10.1016/S1059-1311(97)80008-8
Abstract: The relationship between the degree and distribution of hippoc al atrophy measured by volumetric magnetic resonance imaging and severity of memory deficits in 25 patients with temporal lobe epilepsy secondary to mesial temporal sclerosis was assessed. Hippoc al volumes were expressed as a ratio of smaller to larger, normal ratio greater than 0.95. Neuropsychology tests included: subtests of the WAIS-R, Rey Auditory Verbal Learning Task, Rey Figure and the Austin Maze. Degree of left hippoc al atrophy in patients with left temporal lobe epilepsy was associated with severity of verbal memory deficits as measured by RAVLT total recall (P < 0.05), delayed recall (P < 0.001), story recognition (P < 0.001), list recognition (P < 0.001) and final delayed recall (P < 0.001) and recall of the Rey Figure (P < 0.01). There was no association between degree of right hippoc al atrophy and any of the memory tests. Diffuse left hippoc al atrophy was associated with more severe verbal memory deficits than anterior atrophy. We conclude, the association between degree of left hippoc al atrophy and verbal memory provides further evidence of the predominant involvement of the left hippoc us in verbal memory. The finding of a relationship between degree of left hippoc al atrophy and measures of non-verbal function suggests these tests are dependent on verbal memory, or that mesial temporal sclerosis is a bilateral but asymmetrical condition.
Effective detection of corrected dystrophin loci in mdx mouse myogenic precursors
Publisher: Hindawi Limited
Date: 08-2007
DOI: 10.1002/HUMU.20494
Abstract: Targeted corrective gene conversion (TCGC) holds much promise as a future therapy for many hereditary diseases in humans. Mutation correction frequencies varying between 0.0001% and 40% have been reported using chimeraplasty, oligoplasty, triplex-forming oligonucleotides, and small corrective PCR licons (CPA). However, PCR technologies used to detect correction events risk either falsely indicating or greatly exaggerating the presence of corrected loci. This is a problem that is considerably exacerbated by attempted improvement of the TCGC system using high corrective nucleic acid (CNA) to nuclear ratios. Small fragment homologous replacement (SFHR)-mediated correction of the exon 23 dystrophin (DMD) gene mutation in the mdx mouse model of DMD has been used in this study to evaluate the effect of increasing CPA amounts. In these experiments, we detected extremely high levels of apparently corrected loci and determined that at higher CNA to nuclear ratios the extent of locus correction was highly exaggerated by residual CNA species in the nucleic acids extracted from the treated cells. This study describes a generic locus-specific detection protocol designed to eradicate residual CNA species and avoid the artifactual or exaggerated detection of gene correction.
Eagle syndrome: an unusual cause of head and neck pain
Publisher: American Medical Association (AMA)
Date: 02-2006
Hippocampal volume in first-episode psychoses and chronic schizophrenia: A high-resolution magnetic resonance imaging study
Publisher: American Medical Association (AMA)
Date: 02-1999
DOI: 10.1001/ARCHPSYC.56.2.133
Abstract: It has been proposed that the hippoc us is a potential site for a neurodevelopmental lesion in schizophrenia. While smaller hippoc al volumes have been described in chronic schizophrenia, there have been few magnetic resonance imaging studies in first-episode psychosis. Furthermore, no studies have examined the specificity of this finding to first-episode schizophrenia, compared with first-episode affective psychosis. Hippoc al and whole-brain volumes were estimated using high-resolution magnetic resonance imaging in 140 controls, 46 patients with chronic schizophrenia, and 32 patients with first-episode psychosis. Patients with chronic schizophrenia and first-episode psychosis had significantly smaller hippoc al volumes as compared with controls. Within the first-episode group, both patients with schizophrenia/schizophreniform psychosis and those with affective psychosis had smaller left hippoc al volumes as compared with controls. Smaller right hippoc al volumes were associated with age and illness duration in patients with chronic schizophrenia. Hippoc al volumes were not correlated with age of illness onset or medication dosage in either patient group. These data show that smaller hippoc al volumes are present from the onset of illness. While these findings would support the neurodevelopmental model of schizophrenia, the finding of smaller left hippoc al volume in patients with first-episode schizophrenia and affective psychosis does not support the prediction that smaller hippoc i are specific to schizophrenia. The association of smaller right hippoc al volumes with increased illness duration in chronic schizophrenia suggests either that there is further neurodegeneration after illness onset or that bilateral small hippoc i predict chronicity.
Severe and disabling constipation: An adverse effect of pregabalin
Publisher: Wiley
Date: 06-2009
DOI: 10.1111/J.1528-1167.2009.02381.X
Abstract: The incidence of constipation as an adverse effect of pregabalin has previously been reported as low, with all cases described as either mild or moderate. From the experience of a tertiary referral epilepsy hospital center, we report several cases of severe and disabling constipation after initiating pregabalin, and resolving only on drug withdrawal. Of 80 consecutive patients, six (7.5%) developed significant constipation within 1-2 weeks of commencing pregabalin. Constipation was the most frequent adverse effect that required pregabalin to be withdrawn (6.3% of patients). The severity of symptoms was dose dependent. Pregabalin can cause marked constipation in some patients, and can lead to multiple unnecessary investigations and procedures if the clinician is not aware of this entirely reversible side effect.
Seizure control and treatment in pregnancy: Observations from the EURAP Epilepsy Pregnancy Registry
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-12-2005
DOI: 10.1212/01.WNL.0000195888.51845.80
Abstract: To analyze seizure control and treatment in pregnant women with epilepsy. Seizure control and treatment were recorded prospectively in 1,956 pregnancies of 1,882 women with epilepsy participating in EURAP, an international antiepileptic drugs (AEDs) and pregnancy registry. Of all cases, 58.3% were seizure-free throughout pregnancy. Occurrence of any seizures was associated with localization-related epilepsy (OR: 2.5 1.7 to 3.9) and polytherapy (OR: 9.0 5.6 to 14.8) and for tonic-clonic seizures, with oxcarbazepine monotherapy (OR: 5.4 1.6 to 17.1). Using first trimester as reference, seizure control remained unchanged throughout pregnancy in 63.6%, 92.7% of whom were seizure-free during the entire pregnancy. For those with a change in seizure frequency, 17.3% had an increase and 15.9% a decrease. Seizures occurred during delivery in 60 pregnancies (3.5%), more commonly in women with seizures during pregnancy (OR: 4.8 2.3 to 10.0). There were 36 cases of status epilepticus (12 convulsive), which resulted in stillbirth in one case but no cases of miscarriage or maternal mortality. AED treatment remained unchanged in 62.7% of the pregnancies. The number or dosage of AEDs were more often increased in pregnancies with seizures (OR: 3.6 2.8 to 4.7) and with monotherapy with lamotrigine (OR: 3.8 2.1 to 6.9) or oxcarbazepine (OR: 3.7 1.1 to 12.9). The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported.
In vivo biocompatibility and in vitro characterization of poly-lactide-co-glycolide structures containing levetiracetam, for the treatment of epilepsy
Publisher: Wiley
Date: 21-11-2012
DOI: 10.1002/JBM.A.33208
Abstract: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier. We produced poly-lactide-co-glycolide drop-cast films and wet-spun fibers loaded with the novel antiepileptic drug Levetiracetam, and investigated their morphology, in vitro drug release characteristics, and brain biocompatibility in adult rats. The best performing structures released Levetiracetam constantly for at least 5 months in vitro, and were found to be highly brain biocompatible following month-long implantations in the motor cortex of adult rats. These results demonstrate the potential of polymer-based drug delivery devices in the treatment of epilepsy and warrant their investigation in animal models of focal epilepsy.
Antiepileptic Effects of Lacosamide Loaded Polymers Implanted Subdurally in GAERS
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/6594960
Abstract: The current experiment investigated the ability of coaxial electrospun poly(D,L-lactide-co-glycolide) (PLGA) biodegradable polymer implants loaded with the antiepileptic drugs (AED) lacosamide to reduce seizures following implantation above the motor cortex in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this prospective, randomized, masked experiments, GAERS underwent surgery for implantation of skull electrodes ( n = 6 ), skull electrodes and blank polymers ( n = 6 ), or skull electrodes and lacosamide loaded polymers ( n = 6 ). Thirty-minute electroencephalogram (EEG) recordings were started at day 7 after surgery and continued for eight weeks. The number of SWDs and mean duration of one SWD were compared week-by-week between the three groups. There was no difference in the number of SWDs between any of the groups. However, the mean duration of one SWD was significantly lower in the lacosamide polymer group for up to 7 weeks when compared to the control group ( 0.004 p 0.038 ). The mean duration of one seizure was also lower at weeks 3, 5, 6, and 7 when compared to the blank polymer group ( p = 0.016, 0.037, 0.025, and 0.025, resp.). We have demonstrated that AED loaded PLGA polymer sheets implanted on the surface of the cortex could affect seizure activity in GAERS for a sustained period.
“Truths and roses have thorns about them” – Henry David Thoreau
Publisher: Wiley
Date: 06-2018
DOI: 10.1111/EPI.14433
Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations
Publisher: Springer Science and Business Media LLC
Date: 26-11-2018
DOI: 10.1038/S41593-018-0278-Y
Abstract: The mechanism of seizure emergence and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. We found that the transition to seizure is not a sudden phenomenon, but is instead a slow process that is characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon that is observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We found that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.
Author response: A taxonomy of seizure dynamotypes
Publisher: eLife Sciences Publications, Ltd
Date: 29-05-2020
Engineering a multimodal nerve conduit for repair of injured peripheral nerve
Publisher: IOP Publishing
Date: 03-01-2013
DOI: 10.1088/1741-2560/10/1/016008
Abstract: Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.
Does accounting for seizure frequency variability increase clinical trial power?
Publisher: Elsevier BV
Date: 11-2017
Epilepsy: Ever-changing states of cortical excitability
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.NEUROSCIENCE.2012.07.015
Abstract: It has been proposed that the underlying epileptic process is mediated by changes in both excitatory and inhibitory circuits leading to the formation of hyper-excitable seizure networks. In this review we aim to shed light on the many physiological factors that modulate excitability within these networks. These factors have been discussed extensively in many reviews each as a separate entity and cannot be extensively covered in a single manuscript. Thus for the purpose of this work in which we aim to bring those factors together to explain how they interact with epilepsy, we only provide brief descriptions. We present reported evidence supporting the existence of the epileptic brain in several states interictal, peri-ictal and ictal, each with distinct excitability features. We then provide an overview of how many physiological factors influence the excitatory/inhibitory balance within the interictal state, where the networks are presumed to be functioning normally. We conclude that these changes result in constantly changing states of cortical excitability in patients with epilepsy.
Surgery for temporal lobe epilepsy associated with mesial temporal sclerosis in the older patient
Publisher: Wiley
Date: 06-2010
DOI: 10.1111/J.1528-1167.2009.02430.X
Abstract: To assess the outcomes from temporal lobectomy for hippoc al sclerosis in patients 50 years or older. Controversy exists as to the suitability of older patients for epilepsy surgery, with most of the previous studies demonstrating a correlation between increasing age and poor outcome. However, the inclusion of temporal lobe epilepsy of multiple etiologies has confounded many previous studies of this age group. Twenty-one patients aged 50 years or older (mean 54.9 years) at the time of surgery were included in the study group. All patients had a pathologic diagnosis of hippoc al sclerosis. A retrospective analysis was performed comparing seizure outcomes following a standardized anterior temporal lobectomy with those from 103 patients younger than 50 (mean age 34.7 years) operated upon over the same time period. The mean follow-up period for the study was 9.57 years. Twenty of the 21 patients in the older group (95.2%) had a satisfactory seizure outcome (Engel classes I and II) compared with 90.3% of the younger patients. There was no statistically significant difference in the outcomes between the two groups (p = 0.719). Across both groups of patients combined, there was no significant difference between the mean age in the patients with a satisfactory seizure outcome compared to those with an unsatisfactory outcome (38.3 vs. 34.7 years, p = 0.213). Patients 50 years or older with intractable seizures from hippoc al sclerosis have seizure outcomes following temporal lobectomy that are comparable to young patients over the long term. Older patients should not be denied treatment on the basis of age.
Currents of memory: recent progress, translational challenges, and ethical considerations in fornix deep brain stimulation trials for Alzheimer's disease
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.NEUROBIOLAGING.2017.03.001
Abstract: The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are carefully managed to avoid treatment disenchantment and/or frustration from participants and caregivers. Finally, we urge for collaboration between centers to establish proper clinical standards and to promote better trial results comparison.
Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort study
Publisher: Elsevier BV
Date: 11-2018
Movement related directional tuning from broadband electrocorticography in humans
Publisher: IEEE
Date: 04-2015
Probing for cortical excitability
Publisher: IEEE
Date: 08-2011
Characteristics of motor vehicle crashes associated with seizure: Car crash semiology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-08-2018
DOI: 10.1212/WNL.0000000000006208
Abstract: To examine the characteristics of seizure-related vehicle crashes (SRC). Using a nested case-control design, we identified and compared cases of SRC involving confirmed epilepsy patients with 137,126 non-seizure-related crash controls (NSRC) in the Australian state of Victoria. SRC were identified from approximately 20,000 epileptologist medical records by cross-referencing this source with the Victorian Police Traffic Incident database and the Road Crash Information System Database (RCISD). Seventy-one SRC involving 62 patients with epilepsy were identified. Thirty-seven SRC resulted in injury and could be identified in the RCISD and compared to NSRC. Seizure-related crashes typically involved a single vehicle (57% vs 29%, p 0.001) carrying a sole occupant (95% vs 48%, p = 0.001). Most SRC began with an “out of control movement” (51% vs 10%, p 0.001) and the subsequent collision type differed significantly between the groups ( p 0.001). The majority of SRC were a “collision with a fixed object” (54% vs 17%, p 0.001) involving an “off path on straight” mechanism (48% vs 10%, p 0.001). Regarding all 71 SRC, generalized as compared with focal epilepsy crashes involved younger drivers ( p 0.001), seizure-provoking factors ( p = 0.033), and occurred earlier in the day ( p = 0.004). Given the distinct SRC features, we propose that clinicians, crash investigators, and driver licensing authorities incorporate collision characteristics into the overall assessment of suspected SRC. Further research should examine restricting driving immediately after risk periods as a harm-minimization strategy.
Forecasting Cycles of Seizure Likelihood
Publisher: Cold Spring Harbor Laboratory
Date: 21-12-2019
DOI: 10.1101/2019.12.19.19015453
Abstract: Seizure unpredictability is rated as one of the most challenging aspects of living with epilepsy. Seizure likelihood can be influenced by a range of environmental and physiological factors that are difficult to measure and quantify. However, some generalizable patterns have been demonstrated in seizure onset. A majority of people with epilepsy exhibit circadian rhythms in their seizure times and many also show slower, multiday patterns. Seizure cycles can be measured using a range of recording modalities, including self-reported electronic seizure diaries. This study aimed to develop personalized forecasts from a mobile seizure diary app. Forecasts based on circadian and multiday seizure cycles were tested pseudo-prospectively using data from 33 app users (mean of 103 seizures per subject). In idual’s strongest cycles were estimated from their reported seizure times and used to derive the likelihood of future seizures. The forecasting approach was validated using self-reported events and electrographic seizures from the Neurovista dataset, an existing database of long-term electroencephalography that has been widely used to develop forecasting algorithms. The validation dataset showed that forecasts of seizure likelihood based on self-reported cycles were predictive of electrographic seizures. Forecasts using only mobile app diaries allowed users to spend an average of 62.8% of their time in a low-risk state, with 16.6% of their time in a high-risk warning state. On average, 64.5% of seizures occurred during high-risk states and less than 10% of seizures occurred in low-risk states. Seizure diary apps can provide personalized forecasts of seizure likelihood that are accurate and clinically relevant for electrographic seizures. These results have immediate potential for translation to a prospective seizure forecasting trial using a mobile diary app. It is our hope that seizure forecasting apps will one day give people with epilepsy greater confidence in managing their daily activities.
Tooth-brushing epilepsy
Publisher: Wiley
Date: 07-1996
DOI: 10.1111/J.1528-1157.1996.TB00636.X
Abstract: Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We report a patient with an unusual form of reflex epilepsy in whom seizures are induced by tooth brushing. Magnetic resonance imaging (MRI) demonstrated a right posterior frontal low-grade tumor predominantly involving the precentral gyrus. Video-telemetry demonstrated right-sided epileptiform activity during a typical induced complex partial seizure. An ictal single photon emission computed tomography (SPECT) scan showed an area of hyperfusion that corresponded to the MRI lesion on coregistration with a surface-matching technique. A subsequent coregistered interictal SPECT scan demonstrated hypoperfusion in the same region. Ours is the first report to demonstrate a structural focus in this unusual form of reflex epilepsy. Possible mechanisms to explain the induction of the seizures are discussed.
Patterns of cortical hyperexcitability in adolescent/adult‐onset generalized epilepsies
Publisher: Wiley
Date: 29-03-2013
DOI: 10.1111/EPI.12151
Abstract: To investigate whether using transcranial magnetic stimulation (TMS) to derive if measures of cortical excitability changes can distinguish between various adolescent/adult-onset generalized epilepsy syndromes at different phases of the disorder. One hundred thirty-seven patients with adolescent/adult-onset generalized epilepsy ided into juvenile myoclonic epilepsy, juvenile absence epilepsy, and generalized epilepsy with tonic-clonic seizures only were studied. The cohorts were further ided into drug naive-new onset, refractory, and seizure-free groups. Motor threshold (MT) and paired pulse TMS at short (2, 5, 10, 15 msec) and long (100-300 msec) interstimulus intervals (ISIs) were measured. Results were compared to those of 20 controls. In the drug-naive cohorts MT was reduced (p < 0.05) and cortical excitability increased at 2 and 5 msec and 150, 250, and 300 msec ISIs (p < 0.01) in juvenile myoclonic epilepsy compared to other generalized epilepsy groups and controls. Cortical excitability increased to a lesser degree in other generalized epilepsy syndromes compared to controls, but those two syndromes were not distinguishable from one another. The changes in paired pulse TMS were more prominent in the groups with refractory seizures and very small in the groups who were seizure free. There are syndrome specific changes in cortical excitability associated with generalized epilepsy. These changes are also dependent on seizure control with medication. Juvenile myoclonic epilepsy has a higher cortical excitability profile compared to other adolescent/adult-onset generalized epilepsy syndromes and can be clearly distinguished from them during all phases.
A new era in electroencephalographic monitoring? Subscalp devices for ultra–long‐term recordings
Publisher: Wiley
Date: 27-08-2020
DOI: 10.1111/EPI.16630
Are patterns of cortical hyperexcitability altered in catamenial epilepsy?
Publisher: Wiley
Date: 11-2013
DOI: 10.1002/ANA.23923
Abstract: We used transcranial magnetic stimulation to determine menstrual cycle-related changes in cortical excitability in women with and without catamenial epilepsy and investigated whether these changes differed between ovulatory and anovulatory cohorts. Healthy nonepilepsy women and women with generalized and focal epilepsy were investigated during ovulatory (n=11, 46, and 43, respectively) and anovulatory (n=9, 42, and 41) cycles. Patients were ided based on seizure pattern into catamenial (C1=perimenstrual, C2=periovulatory, C3=luteal seizure exacerbation), noncatamenial, and seizure free. Cortical excitability was assessed using motor threshold (MT) and paired pulse stimulation at short (2-15 milliseconds) and long (100-300 milliseconds) interstimulus intervals twice, at the (1) late follicular and (2) mid luteal phases of the menstrual cycle. In controls, cortical excitability was greatest in the follicular study, where intracortical facilitation was increased (p<0.05). The opposite was seen in women with epilepsy, where intracortical facilitation was greatest and intracortical inhibition was least in the luteal studies (p<0.05). There were no differences between the ovulatory and anovulatory groups in any of the cohorts. No changes were observed in MT. Nonhormonal factors are involved in the cyclicity of cortical excitability across the menstrual cycle. Normal menstrual cycle variations in cortical excitability are altered in a similar pattern in ovulatory and anovulatory women with epilepsy regardless of seizure patterns. The underlying neural changes associated with epilepsy may alter responses to sex hormones. This may be an important underlying mechanism for catamenial seizure clustering.
The Pharmacokinetics and Clinical Therapeutics of the Antiepileptic Drugs
Publisher: Oxford University Press
Date: 12-2012
SPINE AND SPINAL CORD: DEVELOPMENTAL DISORDERS
Publisher: Elsevier
Date: 2002
Development and validation of a seizure initiated drug delivery system for the treatment of epilepsy
Publisher: Elsevier BV
Date: 11-2016
Probing to Observe Neural Dynamics Investigated with Networked Kuramoto Oscillators
Publisher: World Scientific Pub Co Pte Lt
Date: 08-11-2017
DOI: 10.1142/S0129065716500386
Abstract: The expansion of frontiers in neural engineering is dependent on the ability to track, detect and predict dynamics in neural tissue. Recent innovations to elucidate information from electrical recordings of brain dynamics, such as epileptic seizure prediction, have involved switching to an active probing paradigm using electrically evoked recordings rather than traditional passive measurements. This paper positions the advantage of probing in terms of information extraction, by using a coupled oscillator Kuramoto model to represent brain dynamics. While active probing performs better at observing underlying system synchrony in Kuramoto networks, especially in non-Gaussian measurement environments, the benefits diminish with increasing relative size of electrode spatial resolution compared to synchrony area. This suggests probing will be useful for improved characterization of synchrony for suitably dense electrode recordings.
A mechanistic appraisal of cognitive dysfunction in epilepsy
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.NEUBIOREV.2012.05.002
Abstract: A strong relationship between the clinical characteristics of epilepsy and the nature of cognitive impairments associated with the condition has been found, but the nature of this relationship appears to be quite complex and not well understood. This review presents a summary of the research on the interaction between cognition and epilepsy, surveyed from a mechanistic perspective with the aim of clarifying factors that contribute to the co-existence of both disorders. The physiological basis underpinning cognitive processing is first reviewed. The physiology of epilepsy is reviewed, with emphasis placed on interictal discharges and seizures. The nature of the impact of epilepsy on cognition is described, with transient and prolonged effects distinguished. Finally, the complexity of the co-morbidity between cognitive dysfunction and epilepsy is discussed in relation to childhood and adult-onset epilepsy syndromes and severe epileptic encephalopathies. Structural and functional abnormalities exist in patients with epilepsy that may underpin both the cognitive dysfunction and epilepsy, highlighting the complexity of the association. Research, possibly of a longitudinal nature, is needed to elucidate this multifactorial relationship between cognitive dysfunction and epilepsy.
Cortical excitability decreases in Lennox‐Gastaut syndrome
Publisher: Wiley
Date: 19-07-2012
DOI: 10.1111/J.1528-1167.2012.03599.X
Abstract: We used transcranial magnetic stimulation (TMS) to investigate cortical excitability changes in Lennox-Gastaut syndrome (LGS), anticipating we would find a marked increase in excitability compared to other patients with refractory epilepsies. Eighteen patients with LGS were studied. Motor threshold (MT), short intracortical inhibition (paired pulse TMS at 2 and 5 msec interstimulus intervals [ISIs]), intracortical facilitation (10 and 15 msec ISIs), and long intracortical inhibition (100-300 msec ISIs) were measured. Results were compared to those of 20 patients with chronic refractory idiopathic generalized epilepsy (IGE), 20 patients with chronic refractory focal epilepsy, and 20 healthy nonepilepsy controls. A significant decrease in cortical excitability was observed in LGS compared to the other two groups with refractory epilepsy as evidenced by increased MT and intracortical inhibition at both short (2, 5 msec ISIs), and long (100-300 msec ISIs) as well as decreased intracortical facilitation (10, 15 msec ISIs), (p < 0.01 effect sizes ranging from 0.3 to 1.8). Cortical excitability was also lower in LGS compared to nonepilepsy controls (increased MT and decreased intracortical facilitation p < 0.05 effect sizes ranging from 0.5 to 0.9). Interictal cortical excitability is decreased in LGS a feature that distinguishes it from other refractory epilepsy syndromes. This decrease may be an important mechanism for the neurobehavioral comorbidities associated with LGS.
Magnetic resonance imaging study in older fragile X premutation male carriers
Publisher: Wiley
Date: 27-07-2005
DOI: 10.1002/ANA.20542
Abstract: Some carriers of a "premutation" allele of the FMR1 gene develop late-onset tremor/ataxia. We conducted a magnetic resonance imaging volumetric study in an unselected s le of eight older male premutation carriers. Volumetric measures, including total brain volume, and the volumes of cerebrum, cerebellum, and cerebral cortex all were significantly reduced in premutation carriers compared with similar data from 21 age-matched normal controls. Total brain and cerebral volumes were significantly related to the number of CGG repeats in the FMR1 gene. Moreover, increased hippoc al volume indicates this premutation may account for both neurodegenerative and neurodevelopmental changes.
Evaluating the use of prolonged video-EEG monitoring to assess future seizure risk and fitness to drive
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.YEBEH.2010.09.026
Abstract: The use of prolonged video-electroencephalography monitoring (VEM), rather than routine electroencephalography (EEG), in predicting the risk of future seizures in patients with epilepsy is not well studied. A longer period of monitoring could be more likely to capture either ictal or interictal epileptiform activity. This information may better assist clinical decision making on driving fitness. The goal of this study was to evaluate the use of 6-hour prolonged VEM versus routine EEG in the assessment of future seizure risk and driving fitness for patients with epilepsy. Data on consecutive patients referred for 6-hour prolonged VEM were retrospectively analyzed. Criteria were developed that combined EEG findings and clinical factors to determine each patient's fitness to drive. Seizure relapse outcomes were followed over 2 years. Of 34 patients, 27 were considered safe to drive following prolonged VEM. Five (19%) of these 27 patients had seizure relapses all had an obvious precipitant(s) identified including sleep deprivation, excessive alcohol, and missed medication doses. Seven of the 34 patients were deemed unsafe to drive. All seven (100%) had seizure relapses, with unprovoked seizures in four patients. The relative risk of seizure in patients deemed unfit to drive was 5.4 (P=0.00015). If only the routine EEG component of the recordings were used with the criteria, the relative risk would have been 3.4 (P=0.037), with nearly double the number of active drivers having seizures. The majority of patients (76%) in this study had idiopathic generalized epilepsy, with a relative seizure risk of 4.0 (P=0.002) for patients deemed unfit to drive in this subgroup. The focal epilepsy group was small (eight patients) and did not quite achieve statistical significance. Six-hour VEM improves the evaluation of driving fitness by better predicting the risk of subsequent seizure relapse for idiopathic generalized epilepsy and possibly focal epilepsy. Prolonged monitoring is superior to routine EEG. Ongoing avoidance of seizure-provoking factors remains paramount to driving safety.
Long-term assessment of oxcarbazepine in a naturalistic setting: a retrospective study
Publisher: Hindawi Limited
Date: 05-2008
DOI: 10.1111/J.1600-0404.2007.00951.X
Abstract: New antiepileptics seem to be better tolerated by patients. The retention rate of an antiepileptic would be a useful indicator of its practical usefulness. To assess the long-term outcome of oxcarbazepine (OXC) in a naturalistic setting by determining the retention rate. This is a retrospective study. All epilepsy patients treated with OXC at a tertiary care epilepsy center during a period of 3.5 years were included in this study. Retention rates of OXC at 1 and 3 years were estimated for each cohort group using Kaplan-Meier estimates and corresponding 95% confidence intervals. A total of 98 patients were studied. OXC was used as monotherapy in 14 (14.3%) and as add-on therapy in 84 (85.7%). The mean daily dose was 947 +/- 492 mg and 60% received < or = 900 mg/day. Using the Kaplan-Meier survival analysis, the retention rates of OXC at 1 and 3 years were estimated to be 0.853 (0.749-0.956) and 0.737 (0.570-0.904), respectively. OXC is well tolerated by patients as both monotherapy and add-on therapy.
Novel methods of antiepileptic drug delivery -- polymer-based implants.
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.ADDR.2012.04.004
Abstract: Epilepsy is a neurological disorder characterised by spontaneous seizures. Over one third of patients receive insufficient benefit from oral anti-epileptic drug (AED) therapy, and continue to experience seizures whilst on medication. Epilepsy researchers are consequently seeking new ways to deliver AEDs directly to the seizure focus in the brain in order to deliver higher, more effective doses to the seizure focus whilst bypassing the remainder of the brain and body to prevent side effects. The focus of this review will be polymer-based implants, which are polymeric devices loaded with AED that are designed for implantation at the seizure focus in order to achieve gradual, continuous release of AED direct into the region of the brain responsible for seizures. Polymer-based implants produced for epilepsy to date are based on a range of polymers, both biodegradable and non-biodegradable, and range from simple materials development studies through to investigations of implants in animal models of seizures and epilepsy, with varying degrees of success. This review describes the range of methods employed to manufacture polymer-based implants and compares their advantages and potential appeal to industry, and describes and compares the results and successes of polymer-based materials and devices produced to date for the treatment of epilepsy. We also discuss disadvantages and hurdles to be overcome in the field, and describe our predictions for advances to be made in the field in the coming decade.
Exercise-induced seizures and lateral asymmetry in patients with temporal lobe epilepsy
Publisher: Elsevier BV
Date: 2014
Capture of Somatic mtDNA Point Mutations with Severe Effects on Oxidative Phosphorylation in Synaptosome Cybrid Clones from Human Brain
Publisher: Hindawi Limited
Date: 24-11-2014
DOI: 10.1002/HUMU.22694
Abstract: Mitochondrial DNA (mtDNA) is replicated throughout life in postmitotic cells, resulting in higher levels of somatic mutation than in nuclear genes. However, controversy remains as to the importance of low-level mtDNA somatic mutants in cancerous and normal human tissues. To capture somatic mtDNA mutations for functional analysis, we generated synaptosome cybrids from synaptic endings isolated from fresh hippoc us and cortex brain biopsies. We analyzed the whole mtDNA genome from 120 cybrid clones derived from four in idual donors by chemical cleavage of mismatch and Sanger sequencing, scanning around two million base pairs. Seventeen different somatic point mutations were identified, including eight coding region mutations, four of which result in frameshifts. Examination of one cybrid clone with a novel m.2949_2953delCTATT mutation in MT-RNR2 (which encodes mitochondrial 16S rRNA) revealed a severe disruption of mtDNA-encoded protein translation. We also performed functional studies on a homoplasmic nonsense mutation in MT-ND1, previously reported in oncocytomas, and show that both ATP generation and the stability of oxidative phosphorylation complex I are disrupted. As the mtDNA remains locked against direct genetic manipulation, we demonstrate that the synaptosome cybrid approach can capture biologically relevant mtDNA mutants in vitro to study effects on mitochondrial respiratory chain function.
Short-term effects of methylprednisolone on cerebral volume in multiple sclerosis relapses
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.JOCN.2005.08.012
Abstract: We prospectively investigated the short-term effects of intravenous methyl-prednisolone (IVMP) on cerebral volume in patients suffering a multiple sclerosis (MS) relapse. Ten patients underwent MRI brain studies immediately before and after IVMP treatment, and 4 and 8 weeks later. Whole brain volumes decreased significantly over the 8-week period. The greatest change occurred during IVMP administration. This has implications for MS treatment trials using cerebral atrophy as an endpoint.
Atypical EEG abnormalities in genetic generalized epilepsies
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.CLINPH.2015.05.031
Abstract: Bilateral, symmetric and synchronous generalized epileptiform activity is considered to be the typical electroencephalographic (EEG) abnormality in genetic generalized epilepsy (GGE). We sought to study atypical EEG abnormalities in a systematic way based on 24-h ambulatory EEG recordings. The diagnosis of GGE was validated and classified into syndromes according to the International League against Epilepsy criteria. All participants underwent 24-h ambulatory EEG recording. Epileptiform discharges were counted and detailed information was entered into an electronic database. Amplitude asymmetry, focal onset/offset of paroxysms, focal discharges, atypical morphology and generalized paroxysmal fast rhythm were defined as atypical abnormalities. Of the total of 120 patients, 107 had abnormal EEGs, of which 66.4% had at least one atypical epileptiform abnormality on EEG. Atypical morphology was the most frequent abnormality in 93.4% of patients, followed by litude asymmetry (28.0%), focal discharges (21.5%), focal onset of paroxysms (13.1%), focal offset of paroxysms (8.2%) and generalized paroxysmal fast rhythm (1.9%). The analysis of in idual discharges revealed that 76% of paroxysms were of atypical morphology. Significant associations were found between (a) litude asymmetry and state of arousal (p<0.001) as well as seizure-free duration (p 0.013) (b) atypical morphology and state of arousal (p<0.001). In GGE, there are both common and rare atypical epileptiform EEG abnormalities that may vary according to the state of arousal and seizure-free duration. Awareness of these variations is important to avoid misdiagnosis.
The thalamocortical circuit and the generation of epileptic spikes in rat models of focal epilepsy.
Publisher: IEEE
Date: 09-2009
The circadian profile of epilepsy improves seizure forecasting
Publisher: Oxford University Press (OUP)
Date: 26-07-2017
DOI: 10.1093/BRAIN/AWX173
Abstract: It is now established that epilepsy is characterized by periodic dynamics that increase seizure likelihood at certain times of day, and which are highly patient-specific. However, these dynamics are not typically incorporated into seizure prediction algorithms due to the difficulty of estimating patient-specific rhythms from relatively short-term or unreliable data sources. This work outlines a novel framework to develop and assess seizure forecasts, and demonstrates that the predictive power of forecasting models is improved by circadian information. The analyses used long-term, continuous electrocorticography from nine subjects, recorded for an average of 320 days each. We used a large amount of out-of-s le data (a total of 900 days for algorithm training, and 2879 days for testing), enabling the most extensive post hoc investigation into seizure forecasting. We compared the results of an electrocorticography-based logistic regression model, a circadian probability, and a combined electrocorticography and circadian model. For all subjects, clinically relevant seizure prediction results were significant, and the addition of circadian information (combined model) maximized performance across a range of outcome measures. These results represent a proof-of-concept for implementing a circadian forecasting framework, and provide insight into new approaches for improving seizure prediction algorithms. The circadian framework adds very little computational complexity to existing prediction algorithms, and can be implemented using current-generation implant devices, or even non-invasively via surface electrodes using a wearable application. The ability to improve seizure prediction algorithms through straightforward, patient-specific modifications provides promise for increased quality of life and improved safety for patients with epilepsy.
Fractal description of cerebral cortical patterns in frontal lobe epilepsy
Publisher: S. Karger AG
Date: 1995
DOI: 10.1159/000117155
Abstract: The convoluted pattern of normal cerebral cortex resists description by Euclidean geometry. However, subtle abnormalities often unrecognised in vivo may underlie a wide range of neurological disorders. Abnormalities of cortical morphology frequently characterise these lesions, and we applied fractal geometry in an attempt to quantify these abnormalities. We have demonstrated typical fractal scaling properties for the cortical-white matter interface on axial and coronal MR images, with a fractal dimension (Df) of 1.45 +0.06 (mean +1 standard deviation) in normal subjects. We have also applied this to 16 patients with frontal lobe epilepsy, a condition associated with subtle disruptions of the cortical ribbon, all of whom had no obvious abnormality on visual inspection of the images. Nine of these 16 had a Df < 1.27 (mean -3 standard deviations). A control group of 10 patients with temporal lobe epilepsy with a focal foreign tissue lesion (vascular or tumoural) all had Df in the normal range. Analysis of shape using this method identifies subtle abnormalities of the cortical ribbon, and has potential application to images of the human brain in a wide range of clinical and pathophysiological settings.
18F-Flumazenil: A γ-Aminobutyric Acid A–Specific PET Radiotracer for the Localization of Drug-Resistant Temporal Lobe Epilepsy
Publisher: Society of Nuclear Medicine
Date: 15-07-2013
DOI: 10.2967/JNUMED.112.107359
Abstract: Studies report that (11)C-flumazenil (FMZ) PET more specifically localizes the epileptogenic zone in patients with medically refractory focal epilepsy than (18)F-FDG PET. However, practical aspects of (11)C use limit clinical application. We report a phase I/IIa study assessing the clinical use of (18)F-FMZ PET for the localization of the epileptogenic zone in patients with drug-resistant temporal lobe epilepsy (TLE). Receptor binding was quantified using kinetic modeling that did not require arterial s ling. Dynamic (18)F-FMZ PET and static interictal (18)F-FDG PET scans were compared in healthy controls (n = 17 for (18)F-FMZ and n = 20 for (18)F-FDG) and TLE patients with mesial temporal sclerosis on MR imaging (MTS, n = 12) and with normal MR imaging (NL TLE, n = 19). Masked visual assessment of images was undertaken. Parametric images of (18)F-FMZ binding potential (BPND) were generated using the simplified reference tissue model. Region-of-interest analysis on coregistered MR images and statistical parametric mapping were used to quantify (18)F-FMZ BPND and (18)F-FDG uptake in the temporal lobe. The visual assessment of static standardized uptake value images showed (18)F-FMZ PET to have high specificity (16/17 [94%]) and moderate sensitivity (21/31 [68%]) for the localization of the epileptogenic zone, with a more restricted abnormality than (18)F-FDG PET. However, the (18)F-FMZ standardized uptake value images were falsely localizing in 3 of 31 patients (10%). Region-of-interest analysis demonstrated reductions in ipsilateral hippoc al (18)F-FMZ BPND in patients with either MTS or NL TLE, compared with controls subjects. Ipsilateral hippoc al (18)F-FMZ BPND was independent of both hippoc al volume and (18)F-FDG uptake, whereas ipsilateral hippoc al volume was correlated with (18)F-FDG uptake (r(2) = 0.69, P < 0.0001). Statistical parametric mapping analysis demonstrated decreased uptake in 14 of 31 (45%) cases with (18)F-FMZ PET and 18 of 29 (62%) with (18)F-FDG PET. Cluster size was significantly smaller on (18)F-FMZ than (18)F-FDG images (37 vs. 160 voxels, P < 0.01). (18)F-FMZ PET has potential as a clinical tool for the localization of the epileptogenic zone in the presurgical evaluation of drug-resistant TLE, providing information complementary to (18)F-FDG PET, with a more restricted region of abnormality.
DISORDERS OF SMELL AND TASTE
Publisher: Elsevier
Date: 2004
Hippocampal sclerosis in epilepsy and childhood febrile seizures
Publisher: Elsevier BV
Date: 12-1993
DOI: 10.1016/0140-6736(93)92754-H
Abstract: The connection between hippoc al sclerosis and childhood febrile seizures (CFS) is a contentious issue in the study of epilepsy. We investigated 107 patients with drug-resistant epilepsy by high-resolution volumetric magnetic resonance imaging (MRI). 20 had a history of CFS, 45 had focal (26) or diffuse (19) hippoc al volume loss (HVL). The frequency of CFS was significantly (p < 0.001) higher in the patients with HVL, especially of the diffuse pattern, compared to other epileptic patients without HVL and to the general population. Furthermore, the severity of HVL was greatest in those with a history of CFS. No other clinical or demographic features were associated with either a history of CFS or HVL. The frequency of CFS in patients with other structural congenital causes of epilepsy did not differ from that in a general population. Although these findings show that hippoc al sclerosis is strongly associated with a history of CFS, they do not indicate whether this is a causal relationship. If CFS do cause some cases of hippoc al sclerosis, this can not be the only mechanism, as 64% of those with HVL gave no history of CFS. As diffuse HVL is more strongly associated with a history of CFS than focal HVL, it is also possible that CFS convert pre-existing congenital focal abnormalities into diffuse hippoc al sclerosis. Given the possibility that CFS may cause hippoc al damage and epilepsy, they require urgent medical intervention.
Risk factors for injury in a community‐treated cohort of patients with epilepsy in Australia
Publisher: Wiley
Date: 05-02-2019
DOI: 10.1111/EPI.14659
Abstract: There remains a paucity of knowledge regarding specific epilepsy-related risk factors for accidents and injuries in people with epilepsy. Injury studies in people with epilepsy are overrepresented, with tertiary based populations that are prone to bias from severe disease. This study aims to assess the contribution of epilepsy-related risk factors to injuries in a community-based cohort. We performed a retrospective nested case-control study on patients recruited into the Tasmanian Epilepsy Register (TER) from July 1, 2001 to June 30, 2002. The TER is a community-based cohort of patients with epilepsy in Tasmania, Australia, recruited from the national prescription database and interviewed for epilepsy diagnosis, injuries, and risk factors using validated questionnaires with diagnosis made by an epilepsy specialist. The primary outcome measures were lifetime and recent 12-month injury. Multivariate logistic regression with multiple imputation modeling responder nondisclosure was performed, adjusting for age, gender, region, socioeconomic status, seizure frequency, and epilepsy duration. A total of 819 patients with epilepsy were included in this study. Ten percent of patients experienced an injury in the preceding year. Before adjusting for seizure frequency, any seizure over the past 12 months was associated with recent injury (adjusted odds ratio [OR] = 7.90, 95% confidence interval [CI] = 4.17-14.96). Impaired awareness, cluster seizures, sleep-only seizures, and convulsive seizure were characteristics found to significantly influence injuries irrespective of seizure frequency. Although a warning appeared initially protective for recent injuries (OR = 0.39, 95% CI = 0.22-0.69), this was entirely explained by seizure frequency, with the effect becoming nonsignificant. Likely due to their unpredictable nature, seizures expose patients with epilepsy to a high risk of life-threatening injury. These findings emphasize the importance of seizure freedom for maximizing the safety of patients with epilepsy.
Seizure Forecasting Using a Novel Sub-Scalp Ultra-Long Term EEG Monitoring System
Publisher: Cold Spring Harbor Laboratory
Date: 11-05-2021
DOI: 10.1101/2021.05.09.21256558
Abstract: Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder™), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilising cycles in EA and previous seizure times. The procedures and devices were well tolerated, and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88) is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.
Measurement invariance of core cognitive abilities in heterogeneous neurological and community samples
Publisher: Elsevier BV
Date: 08-2004
Focal seizure symptoms in idiopathic generalized epilepsiesAuthor Response
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-02-2016
MRI-based hippocampal volumetrics: Data acquisition, normal ranges, and optimal protocol
Publisher: Elsevier BV
Date: 1995
DOI: 10.1016/0730-725X(95)02013-J
Abstract: The process of producing magnetic resonance (MR) volume measurements can be ided into considerations of acquisition and postprocessing of the MR data. With careful attention to both of these, precise and reproducible measurements can be achieved. A statistical description of hippoc al measurements in normal volunteers must be available for comparison if volumetrics are employed either for clinical or research purposes. A wide range in "normal" hippoc al volume is present in the studies of normal young adults that have been reported to date. This variability is most probably due to interinstitutional differences in hippoc al boundary criteria, and in the software employed for counting pixels in a defined region of interest (ROI). Because the numeric output from the volume measurement procedure is highly technique-dependent, the statistical description of "normal" should be determined or calibrated at each institution wishing to use these techniques.
Sinus node arrest secondary to HSV encephalitis
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.JOCN.2006.06.017
Abstract: We report a patient with herpes simplex virus (HSV) encephalitis presenting as recurrent syncope due to sinus node arrest. Although the patient's initial presentation suggested a primary cardiac cause, an eventual diagnosis of HSV encephalitis was supported by computed tomography scan and magnetic resonance imaging, and confirmed by HSV polymerase chain reaction. The mechanism of cardiac arrhythmias in HSV encephalitis remains unclear however, cardiac monitoring should be considered in all patients in whom the diagnosis is suspected. With diagnosis and appropriate management, a permanent pacemaker is generally not indicated. This case report highlights the importance of considering potentially reversible causes of collapse secondary to sinus node dysfunction beyond primary cardiac causes.
Recurrent intramedullary sarcoidosis
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.JOCN.2005.08.009
Abstract: We present a 47-year-old man with recurrent intramedullary sarcoidosis. This condition, without any other manifestations of the disease, is rare, with less than 20 reports in the literature. Further, to our knowledge our presentation is the only reported case of intramedullary sarcoidosis recurring in a separate, distant region of the cord after a period of treatment with steroids, to which the patient had initially responded.
Image guided audit of surgery for temporal lobe epilepsy
Publisher: BMJ
Date: 10-1994
Abstract: Studies on surgery for temporal lobe epilepsy are h ered by lack of information about the actual surgery that has taken place. A method is described for accurately measuring the volumes of resection by MRI after surgery. Ten cases of surgically treated temporal lobe epilepsy (nine non-tailored resections, one selective amygdalohippoc ectomy) are presented to show the technique. Indices of extent of resection in both the mesiobasal and lateral temporal lobe compartments have been measured, compared, and evaluated. By comparison with identical preoperative volumetric MRI the hippoc al resections have been correlated with the demonstrated hippoc al volume loss, thought to be of relevance in the aetiology of temporal lobe epilepsy. Detailed postoperative audit in this manner is vital in providing a rational basis for follow up studies of outcome.
A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy
Publisher: Elsevier BV
Date: 12-2017
Three-dimensional neural cultures produce networks that mimic native brain activity
Publisher: Hindawi Limited
Date: 12-12-2018
DOI: 10.1002/TERM.2508
Abstract: Development of brain function is critically dependent on neuronal networks organized through three dimensions. Culture of central nervous system neurons has traditionally been limited to two dimensions, restricting growth patterns and network formation to a single plane. Here, with the use of multichannel extracellular microelectrode arrays, we demonstrate that neurons cultured in a true three-dimensional environment recapitulate native neuronal network formation and produce functional outcomes more akin to in vivo neuronal network activity.
Tremor/ataxia syndrome and fragile X premutation: Diagnostic caveats
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.JOCN.2006.01.015
Abstract: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly discovered late-onset neurodegenerative disorder caused by a premutation in the FMR1 X-linked gene. We present ex les of a discrepancy between obvious brain changes observed on MRI, and minimal clinical neurological manifestations in three older carriers of this premutation. This discrepancy occurred in three of nine carriers ascertained in an unbiased manner. If the systematic follow-up studies of adult carriers confirm this trend, this will have an impact on early diagnosis of neurological involvement and possible prevention. If MRI changes precede clinical manifestation of FXTAS this may explain the low detection rate of fragile X carriers among patients with neurological syndromes associated with tremor/ataxia.
The neurologist, psychogenic nonepileptic seizures, and borderline personality disorder
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.YEBEH.2007.09.010
Abstract: Patients with psychogenic nonepileptic seizures (PNES) are common in tertiary epilepsy centers, emergency departments, and neurological practices. Psychiatric discussion of patients with PNES has emphasized the role of trauma and dissociation. Personality disorder has been considered, but its extensive implications for neurological management have not been fully appreciated. We propose that the most difficult aspects of management stem not from the convulsive episodes, but from the personality disorder that frequently accompanies them. Although it is not the neurologist's role to treat personality disorder, the conduct of the physician-patient relationship can have potent consequences for good or ill on the outcome. We present a brief guide to current concepts of personality disorder discuss the literature concerning its association with PNES, and offer practical guidelines for the conduct of the neurologist-patient relationship. This perspective offers resolutions to longstanding controversies, including how to communicate the diagnosis, discontinuing medication, and ongoing neurological contact.
The cortical excitability profile of temporal lobe epilepsy
Publisher: Wiley
Date: 20-09-2013
DOI: 10.1111/EPI.12374
Abstract: Transcranial magnetic stimulation (TMS) was used to characterize measurable changes of cortical excitability in patients who were undergoing medical and surgical management of temporal lobe epilepsy (TLE) to investigate whether these alterations depended on timing of achieving seizure control throughout the course of illness and method of management. Eighty-five patients with TLE ided into (1) drug naive-new onset, (2) early medically refractor, and (3) late medically refractory, (4) early seizure-free on antiepileptic drugs, and (5) late seizure-free on antiepileptic drugs, (6) postoperative refractory, and (7) postoperative seizure-free groups were studied. Motor threshold (MT) and paired-pulse TMS at short (2, 5, 10, and 15 msec) and long (100-300 msec) interstimulus intervals (ISIs) were measured. Results were compared to those of 20 controls. A significant interhemispheric difference was observed early at onset prior to starting medication, with higher cortical excitability in the hemisphere ipsilateral to the seizure focus, whereas the unaffected hemisphere was normal. After that, cortical excitability was higher in both hemispheres in the refractory groups (medical and postoperative) compared to the seizure-free and drug-naive groups (p < 0.05). This effect was most prominent at the long ISIs. Changes in cortical excitability seen in patients with TLE are influenced by the course of the disease. The alterations that occur due to epilepsy are closely related to course of illness and degree/timing of seizure control. Successful management leads to resolution of this cortical hyperexcitability in a similar fashion regardless of method: medication (intact generator, but modulated by drugs) or surgery (generator removed).
Mortality in patients with psychogenic nonepileptic seizures
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-07-2020
DOI: 10.1212/WNL.0000000000009855
Abstract: To investigate the hypothesis that patients diagnosed with psychogenic nonepileptic seizures (PNES) on video-EEG monitoring (VEM) have increased mortality by comparison to the general population. This retrospective cohort study included patients evaluated in VEM units of 3 tertiary hospitals in Melbourne, Australia, between January 1, 1995, and December 31, 2015. Diagnosis was based on consensus opinion of experienced epileptologists and neuropsychiatrists at each hospital. Mortality was determined in patients diagnosed with PNES, epilepsy, or both conditions by linkage to the Australian National Death Index. Lifetime history of psychiatric disorders in PNES was determined from formal neuropsychiatric reports. A total of 5,508 patients underwent VEM. A total of 674 (12.2%) were diagnosed with PNES, 3064 (55.6%) with epilepsy, 175 (3.2%) with both conditions, and 1,595 (29.0%) received other diagnoses or had no diagnosis made. The standardized mortality ratio (SMR) of patients diagnosed with PNES was 2.5 (95% confidence interval [CI] 2.0–3.3). Those younger than 30 had an 8-fold higher risk of death (95% CI 3.4–19.8). Direct comparison revealed no significant difference in mortality rate between diagnostic groups. Among deaths in patients diagnosed with PNES (n = 55), external causes contributed 18%, with 20% of deaths in those younger than 50 years attributed to suicide, and “epilepsy” was recorded as the cause of death in 24%. Patients diagnosed with PNES have a SMR 2.5 times above the general population, dying at a rate comparable to those with drug-resistant epilepsy. This emphasizes the importance of prompt diagnosis, identification of risk factors, and implementation of appropriate strategies to prevent potential avoidable deaths.
The dynamics of the epileptic brain reveal long memory processes
Publisher: Frontiers Media SA
Date: 24-10-2014
Preliminary results of the global audit of treatment of refractory status epilepticus
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.YEBEH.2015.04.010
Abstract: The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus".
Familial dystonic choreoathetosis with myokymia; A sleep responsive disorder
Publisher: BMJ
Date: 12-1951
Abstract: A family is presented with paroxysmal dystonic choreoathetosis transmitted as a dominant trait over five generations. The family is unusual in the marked responsiveness of the episodes to short periods of sleep in several members, in the very variable age of onset, and in the association with prominent myokymia in some cases. These overlap features suggest a link between paroxysmal dystonic choreoathetosis and familial paroxysmal ataxia with myokymia.
Evaluating the Utility of Inpatient Video‐EEG Monitoring
Publisher: Wiley
Date: 21-07-2004
Three-dimensional fractal analysis of the white matter surface from magnetic resonance images of the human brain
Publisher: Oxford University Press (OUP)
Date: 1996
Abstract: The convolutions of the cerebral cortex are difficult to describe and delineate. Our understanding of the development of the brain and its associated maldevelopment would be assisted by quantitative analysis of the cortex. Volumetric magnetic resonance (MR) imaging provides high-resolution anatomical data from which we can reconstruct the white matter as a three-dimensional object and extract its surface (the grey/white matter interface). Three-dimensional fractal analysis of this surface is a method of quantifying the surface complexity dependent upon the variation of the surface area under different scales of inspection. We estimate the fractal dimension of the white matter surface for each hemisphere and 10 coronal blocks of each hemisphere in 30 normal adult subjects. These values are tightly distributed and have been used to define a normal range of fractal dimensions. Abnormal fractal dimensions were found in 8/16 subjects with epilepsy and a gyral abnormality observed on routine MR imaging and in 9/23 subjects with epilepsy and normal routine MR imaging. These analytical techniques offer additional information about the structure of the cortex in normal brains and about abnormalities of structure in subjects with suspected but unobserved structural abnormalities.
Amyloid Precursor Protein Mediates Neuronal Protection from Rotenone Toxicity
Publisher: Springer Science and Business Media LLC
Date: 05-01-2019
Cerebral and cerebellar volume reduction in children with intractable epilepsy
Publisher: Wiley
Date: 11-2000
DOI: 10.1111/J.1528-1157.2000.TB00122.X
Abstract: Adult epilepsy studies have demonstrated cerebral and cerebellar volume reduction beyond the epileptogenic zone, correlating this with an inferior surgical outcome. We determined whether brain volumes were reduced in childhood epilepsy and the significance of this. Cerebral, cerebellar, and hippoc al volumes were measured by quantitative magnetic resonance imaging on 112 children (ages 4-18) with epilepsy syndrome determined by video-EEG telemetry. Eighty-seven had partial epilepsy and 25 had generalized epilepsy or indeterminate syndrome. Normative volumes were obtained from 44 child controls from the community. A significant reduction in cerebral (12.6%) and cerebellar (7.9%) volume was present in the epilepsy group compared with controls. Analysis of subgroups revealed that cerebral volume was significantly decreased in frontal lobe and nonlocalized partial epilepsies. The mean hippoc al ratio of 0.73 for mesial temporal lobe epilepsy was significantly less than for all other syndromes and controls. There was no difference in the rate of hippoc al volume reduction between syndromes. There was a significant correlation between IQ and cerebral and cerebellar volume, but not duration or age of onset of epilepsy. Cerebral and cerebellar volume reduction is common in intractable epilepsy syndromes of childhood. These cross-sectional data suggest that brain volume reduction is present at epilepsy onset and is not a result of intractable seizures. Hippoc al asymmetry is more sensitive than volume reduction as a marker for mesial temporal lobe epilepsy, but neither measure is specific.
Non-invasive investigations successfully select patients for temporal lobe surgery
Publisher: BMJ
Date: 09-1997
Abstract: There is controversy regarding the need for invasive monitoring in the preoperative assessment of patients with temporal lobe epilepsy. The use of a series of non-invasive investigations in identifying the seizure focus is reported in 75 consecutive adults referred for epilepsy surgery. All had video-EEG monitoring using scalp electrodes, high resolution MRI, and neuropsychology assessment. Other investigations included volumetric MRI, PET, and ictal and interictal SPECT. The seizure focus was localised and surgery offered if MRI disclosed unilateral hippoc al atrophy or a foreign tissue lesion and other investigations were either concordant or not discordant. In 68 patients the seizure focus was localised and three patients were inoperable. Sixty five patients have been offered surgery and 50 have undergone temporal lobe surgery and have a follow up of at least 12 months (mean 24 months). All had pathology: hippoc al sclerosis 34, dysembryoblastic neuroepithelial tumour six, cavernoma four, dysplasia two, low grade glioma two, ganglioglioma two. Thirty nine patients (78%) are seizure free postoperatively, 29/34 with hippoc al sclerosis and 10/16 with a foreign tissue lesion. Of the 11 patients with postoperative recurrent seizures, eight have a >90% reduction in seizure frequency and three have <90% reduction in seizure frequency but a worthwhile improvement. Non-invasive investigations successfully select most patients for temporal lobe surgery.
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