ORCID Profile
0000-0001-6032-4347
Current Organisation
University of Melbourne
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Publisher: American Medical Association (AMA)
Date: 09-2020
Publisher: American Chemical Society (ACS)
Date: 03-04-2020
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.
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.
Publisher: IEEE
Date: 09-2009
Publisher: Elsevier BV
Date: 08-2023
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.
Publisher: American Medical Association (AMA)
Date: 12-2022
DOI: 10.1001/JAMANEUROL.2022.3479
Abstract: This case report describes a patient with anti–leucine-rich glioma-inactivated 1 (LGI1)–associated hyperexcitability syndrome associated with myopathy.
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.
Publisher: Bentham Science Publishers Ltd.
Date: 07-2009
DOI: 10.2174/187152709788680698
Abstract: Polymer based therapies offer many potential advantages in the treatment of diseases of the nervous system, and would allow delivery of therapeutic agents directly to the relevant area of brain, circumventing obstacles presented by the blood brain barrier, avoiding the side-effects often associated with systemic medication administration, and permitting much smaller doses of medication. As improvements in diagnostic procedures, particularly imaging, now provide very accurate localization of therapeutic targets in many of these conditions, it is technically feasible to deliver such agents precisely to the relevant brain region. Combined with advances in polymer sciences, there is renewed interest in focal drug delivery systems, particularly around intelligent or controlled release systems which would extend the life-span of these devices considerably. Major obstacles remain, however, particularly around the safety and biocompatibility of such materials, and the complexity of testing in clinical scenarios. We review here the current status of animal and human studies in this rapidly evolving area, addressing some of the practical obstacles and examining the range of potential applications in chronic neurological disease.
Publisher: Wiley
Date: 26-06-2022
DOI: 10.1111/EPI.17327
Abstract: Autoimmune encephalitis (AE) is a neurological disorder caused by autoimmune attack on cerebral proteins. Experts currently recommend staged immunotherapeutic management, with first-line immunotherapy followed by second-line immunotherapy if response to first-line therapy is inadequate. Meta-analysis of the evidence base may provide higher quality evidence to support this recommendation. We undertook a systematic review of observational cohort studies reporting AE patients treated with either second-line immunotherapy or first-line immunotherapy alone, and outcomes reported using the modified Rankin Scale (mRS search date: April 22, 2020). We performed several one-stage multilevel in idual patient data (IPD) meta-analyses to examine the association between second-line immunotherapy and final mRS scores (PROSPERO ID CRD42020181805). IPD were obtained for 356 patients from 25 studies. Most studies were rated as moderate to high risk of bias. Seventy-one patients (71/356, 19%) were treated with second-line immunotherapy. We did not find a statistically significant association between treatment with second-line immunotherapy and final mRS score for the cohort overall (odds ratio [OR] = 1.74, 95% confidence interval [CI] = .98-3.08, p = .057), or subgroups with anti-N-methyl-D-aspartate receptor encephalitis (OR = 1.03, 95% CI = .45-2.38, p = .944) or severe AE (maximum mRS score > 2 OR = 1.673, 95% CI = .93-3.00, p = .085). Treatment with second-line immunotherapy was associated with higher final mRS scores in subgroups with anti-leucine-rich glioma-inactivated 1 AE (OR = 6.70, 95% CI = 1.28-35.1, p = .024) and long-term (at least 12 months) follow-up (OR = 3.94, 95% CI = 1.67-9.27, p = .002). We did not observe an association between treatment with second-line immunotherapy and lower final mRS scores in patients with AE. This result should be interpreted with caution, given the risk of bias, limited adjustment for disease severity, and insensitivity of the mRS in estimating psychiatric and cognitive disability.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.EPLEPSYRES.2021.106846
Abstract: Outcomes of status epilepticus have not substantially changed over the last decade. Given onset is most often in the community, early termination strategies that are implementable outside of hospitals are of public health importance. This 10-year retrospective single-centre cohort study aimed to determine whether pre-hospital benzodiazepine administration is associated with improved health outcomes in patients with out-of-hospital onset status epilepticus. We reviewed the medical records of all patients admitted with status epilepticus between 2008 and 2018 at St Vincent's Hospital Melbourne. Data regarding onset setting, medical history, management and outcomes were extracted. 72 patients meeting inclusion criteria were identified. Onset of status epilepticus was out-of-hospital for 74% (53/72) of patients, 66% (35/53) of whom were administered a benzodiazepine before reaching hospital, most often by ambulance officers (30/35, 86%). Pre-hospital benzodiazepine administration was associated with a 90% reduction in duration time to seizure cessation (0.65 vs 5.8 days, p = 0.012) and 50% reduction in length of hospital stay (7.6 vs 15.8 days, p = 0.045). In-hospital onset status epilepticus was associated with higher mortality than out-of-hospital onset (26% vs 4%, RR 6.5, p = 0.004). Pre-hospital benzodiazepines shorten the time to seizure control and length of hospital stay in patients with out-of-hospital status epilepticus, although is under-utilised by both ambulance staff and home carers. Health policy measures to improve ambulance officer and home carer administration skills and confidence may address these issues.
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.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Springer Science and Business Media LLC
Date: 08-12-2022
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.
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.
Publisher: Sciedu Press
Date: 18-02-2016
DOI: 10.5430/CRIM.V3N1P67
Publisher: Springer Science and Business Media LLC
Date: 20-11-2020
DOI: 10.1038/S41531-020-00136-9
Abstract: Medical conditions with effective therapies are usually managed with objective measurement and therapeutic targets. Parkinson’s disease has effective therapies, but continuous objective measurement has only recently become available. This blinded, controlled study examined whether management of Parkinson’s disease was improved when clinical assessment and therapeutic decisions were aided by objective measurement. The primary endpoint was improvement in the Movement Disorder Society-United Parkinson’s Disease Rating Scale’s (MDS-UPDRS) Total Score. In one arm, objective measurement assisted doctors to alter therapy over successive visits until objective measurement scores were in target. Patients in the other arm were conventionally assessed and therapies were changed until judged optimal. There were 75 subjects in the objective measurement arm and 79 in the arm with conventional assessment and treatment. There were statistically significant improvements in the moderate clinically meaningful range in the MDS-UPDRS Total, III, IV scales in the arm using objective measurement, but not in the conventionally treated arm. These findings show that global motor and non-motor disability is improved when management of Parkinson’s disease is assisted by objective measurement.
No related grants have been discovered for Amy Halliday.