ORCID Profile
0000-0003-0527-3932
Current Organisation
Westmead Hospital
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Publisher: American Physiological Society
Date: 12-2006
Abstract: Recent studies suggest that beta (15–30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. In this study, we recorded both LFP and neuronal spike activity from the STN in 14 PD patients during functional neurosurgery. Of 200 single- and multiunit recordings 56 showed significant oscillatory activity at about 26 Hz and 89% of these were coherent with the simultaneously recorded LFP. The incidence of neuronal beta oscillatory activity was significantly higher in the dorsal STN ( P = 0.01) and corresponds to the significantly increased LFP beta power recorded in the same region. Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.
Publisher: Elsevier BV
Date: 05-2004
Publisher: Wiley
Date: 04-2003
DOI: 10.1002/MDS.10382
Abstract: We report on a patient with spontaneous and stimulus-sensitive myoclonic jerks and dystonia of the right leg that had been present since infancy. Magnetic resonance imaging showed a linear area of gliosis confined to the left posterolateral putamen. This is the first report of focal myoclonus-dystonia of the lower limb secondary to a putaminal lesion.
Publisher: Wiley
Date: 12-11-2014
DOI: 10.1002/MDS.25719
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.JOCN.2012.03.016
Abstract: The mechanism of motor weakness in patients with Miller-Fisher syndrome (MFS) remains to be fully elucidated. We performed stimulated single fibre electromyography (sSFEMG) in a clinically weak frontalis muscle in a patient with MFS. Stimulate single fiber EMG revealed increased jitter in over 50% of the apparent single fibre action potentials from the frontalis muscle in addition to increased mean jitter. The findings in the present study suggest dysfunction of neuromuscular transmission in patients with MFS.
Publisher: Wiley
Date: 20-11-2013
DOI: 10.1002/MDS.25739
Abstract: Proximal-dominant upper limb tremor is highly disabling, and there is no effective medical therapy. In this study, we evaluated the efficacy of botulinum toxin (BTX) injections for the treatment of proximal tremor. We conducted a retrospective analysis of open-label treatment with BTX in 19 patients with proximal tremor. The response to therapy was graded into four categories according to self-reported improvements in tremor and function. In total, 63% of patients reported moderate or marked benefit, defined as functional improvements sufficient enough to allow feeding or drinking from a cup whereas 21% of patients reported mild benefit and 15% of patients reported no benefit. One patient developed severe weakness of shoulder abduction and withdrew from the treatment otherwise, the therapy was free of side effects. The current findings support the efficacy of BTX therapy in the treatment of proximal upper limb tremor with minimal side effects.
Publisher: SAGE Publications
Date: 26-08-2013
DOI: 10.1111/IJS.12132
Abstract: No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation ‘spot sign’ will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4·5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth – AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale , intracerebral hemorrhage volume ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either % or ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636.
Publisher: Elsevier BV
Date: 09-2000
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.JOCN.2013.03.035
Abstract: Truncal predominant tar e dystonia is an uncommon presentation of dystonia, and may be associated with significant disability. We report a patient with near-complete resolution of severe, disabling truncal tar e dystonia following globus pallidus pars interna deep brain stimulation. Her unusual clinical presentation highlights the difficulties in diagnosing unusual forms of dystonia, and the therapeutic gains that can be achieved once the diagnosis is recognised.
Publisher: Oxford University Press (OUP)
Date: 09-11-2005
Abstract: The aim of this paper is to explain critical features of the human primary generalized epilepsies by investigating the dynamical bifurcations of a nonlinear model of the brain's mean field dynamics. The model treats the cortex as a medium for the propagation of waves of electrical activity, incorporating key physiological processes such as propagation delays, membrane physiology, and corticothalamic feedback. Previous analyses have demonstrated its descriptive validity in a wide range of healthy states and yielded specific predictions with regards to seizure phenomena. We show that mapping the structure of the nonlinear bifurcation set predicts a number of crucial dynamic processes, including the onset of periodic and chaotic dynamics as well as multistability. Quantitative study of electrophysiological data supports the validity of these predictions. Hence, we argue that the core electrophysiological and cognitive differences between tonic-clonic and absence seizures are predicted and interrelated by the global bifurcation diagram of the model's dynamics. The present study is the first to present a unifying explanation of these generalized seizures using the bifurcation analysis of a dynamical model of the brain.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JOCN.2013.02.032
Abstract: Impulse control and related disorders (ICRD) are not uncommon in patients with idiopathic Parkinson's disease (PD). The present study aimed to investigate the effects of ICRD on quality of life (QoL) and disability in PD. From two movement disorder clinics in Sydney, Australia, 100 consecutive patients with PD were included in the trial. The Unified Parkinson's Disease Rating Scale (UPDRS), Mini Mental State Examination and the Parkinson's Disease Questionnaire-39 were used to measure disease severity, cognition and disease-specific QoL. The diagnosis of ICRD was based on face-to-face structured clinical interviews by three psychiatrists with experience in ICRD using the Expanded Structured Clinical Interview for the Diagnostic and Statistical Manual IV for Obsessive-Compulsive Disorder Related/Spectrum Disorders. ICRD were present in 15% of our patient population, and had a negative impact on QoL and Activity of Daily Living (ADL) scores. After adjusting for the presence of major depressive disorders and PD duration, the effect on emotional wellbeing remained statistically significant (p<0.004). Disease duration also correlated with worse QoL and ADL scores. Major depression disorders reduced QoL but not ADL. Patients with ICRD tended to suffer more from depression than those without ICRD. There were no statistically significant differences in age, sex, major depressive disorders, PD duration, total levodopa equivalent daily dose, use of dopamine agonists, or UPDRS motor score between patients with and without ICDR.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.EXPNEUROL.2007.01.010
Abstract: We examined the effects of a sensory trick (SeT) on cortical EEG and globus pallidus (GP) local field potentials in four cervical dystonia patients, two of whom had an effective SeT and two who did not. The application of an effective SeT was associated with bilateral desynchronization in the 6-8 Hz and beta bands in the GP and sensorimotor cortical regions. In contrast, mimicking an SeT led to a worsening of dystonia, which was associated with desynchronization of the beta band and synchronization in the 4-6 Hz range. These preliminary findings suggest a role for 4-8 Hz frequency synchronization in the pathophysiology of dystonia.
Publisher: Elsevier BV
Date: 11-2012
Publisher: American Physiological Society
Date: 08-2007
Abstract: Cervical dystonia (CD) is a movement disorder that involves involuntary turning and twisting of the neck caused by abnormal muscle contraction. Deep brain stimulation (DBS) in the globus pallidus internus (GPi) is used to treat both CD and the motor symptoms of Parkinson's disease (PD). It has been suggested that the differing motor symptoms in CD and PD may arise from a decreased GPi output in CD and elevation of output in PD. To test this hypothesis, extracellular recordings of GPi neuronal activity were obtained during stereotactic surgery for the implantation of DBS electrodes in seven idiopathic CD and 14 PD patients. The mean GPi neuronal firing rate recorded from CD patients was lower than that in PD patients ( P 0.001 means ± SE: 71.4 ± 2.2 and 91.7 ± 3.0 Hz, respectively). Furthermore, GPi neurons fired in a more irregular pattern consisting of more frequent and longer pauses in CD compared with PD patients. When comparisons were done based on locations of recordings, these differences in firing rates and patterns were limited to the ventral portion of the GPi. In contrast, no difference in firing rate or pattern was observed in the globus pallidus externus between the two groups. These findings suggest that alterations in both firing rate and firing pattern may underlie the differing motor symptoms associated with these two movement disorders.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2023
DOI: 10.1038/S41531-023-00525-W
Abstract: Comparative studies assessing outcomes with the three device-assisted therapies could help to in idualise treatment for patients living with Parkinson’s disease. We designed a single-centre non-randomised prospective observational study assessing the quality of life (QoL), motor and non-motor outcomes at 6 and 12-months in patients treated with subcutaneous apomorphine continuous 16-hours infusion (APO), levodopa-carbidopa intestinal gel (LCIG) or subthalamic nucleus deep brain stimulation (STN-DBS). In this study, 66 patients were included (13 APO 19 LCIG 34 STN-DBS). At baseline, cognitive, non-motor and motor scores were significantly less severe in the STN-DBS group, whereas the LCIG group had a longer disease duration and higher non-motor scores. In the APO group, there were no statistically significant changes in non-motor, motor and QoL scales. The LCIG group had significant changes in QoL and motor scales that were significant after multiple comparison analysis at 6 and 12-months. The STN-DBS group showed improvement in QoL scores and non-motor and motor scores at 6 and 12-months after multiple comparison analysis. In this real-life prospective study, device-assisted therapies showed differences in their effects on QoL and motor and non-motor function at 12-months. However, there were also differences in baseline characteristics of the patient groups that were not based on pre-determined selection criteria. Differences in characteristics of patients offered and/or treatment with different device-assisted therapies may reflect within-centre biases that may, in turn, influence perceptions of treatment efficacy or outcomes. Treatment centres should be aware of this potential confounder when assessing and offering device-assisted treatment options to their patients and potential baseline differences need to be taken into consideration when comparing the results of non-randomised studies.
Publisher: Wiley
Date: 08-04-2020
DOI: 10.1002/PRI.1840
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JOCN.2015.05.059
Abstract: We report the efficacy and adverse effect profile of intraduodenal levodopa-carbidopa intestinal gel (LCIG) infusion from patients treated in a single Australian movement disorder centre. We conducted an open-label, 12 month prospective study of treatment with LCIG in patients with advanced Parkinson's disease in a single tertiary referral hospital unit specialising in movement disorders. Patients with levodopa-responsive, advanced Parkinson's disease with motor fluctuations despite optimal pharmacological treatment were enrolled and underwent a 16 hour daily infusion of LCIG for 12 months. Fifteen participants completed the trial. The mean (± standard deviation) improvement in Unified Parkinson's Disease Rating Scale part III was 37 ± 11%, mean daily "off" period reduced from 6.3 ± 2 to 1.9 ± 2 hours, total daily "on" time increased from 10.2 ± 3 to 13.7 ± 2 hours, "on" period without dyskinesia increased from 4.5 ± 3 to 7.5 ± 5 hours, and 39-item Parkinson's Disease Questionnaire Summary Index score improved by 32.5 ± 35%. The most common adverse event was reversible peripheral neuropathy secondary to vitamin B12 ± B6 deficiency (40%), local tube problems (40%), and impulse control disorder (ICD) (27%). No patient had stoma bleeding or peritonitis. All patients with ICD had a past psychiatric diagnosis of depression with or without anxiety and a higher daily levodopa intake at 6 and 12 months of LCIG infusion. Intraduodenal LCIG improves motor performance, quality of life and daily "on" period. Prior to and during duodenal LCIG infusion, clinicians should monitor for peripheral neuropathy and vitamin B12 and B6 deficiency, as supplementation can reverse peripheral neuropathy. This trial is registered at Clinicaltrials.gov as CT00335153.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2005
DOI: 10.1007/S00221-005-2359-X
Abstract: According to the now classical basal ganglia-thalamocortical circuitry model, the chorea of Huntington's disease (HD) and the hypokinesia in Parkinson's disease (PD) are explained by a decrease in the inhibitory output (reduced firing rates) from the globus pallidus internus (GPi) in HD and increased output in PD. Differences between firing patterns might also be a factor contributing to the different symptoms, however. To test the predictions of the model we examined neuronal firing rates and patterns in two HD patients and 14 PD patients. Single-cell, microelectrode recordings were obtained from awake patients undergoing stereotactic surgery for implantation of deep brain stimulating (DBS) electrodes in the GPi. The mean neuronal firing rate in the GPi of HD patients was 81.8+/-4.3 Hz (mean+/-SEM), which was not significantly different from that in PD patients (89.9+/-3.0 Hz). Firing pattern analyses using measurements of burst index, coefficient of variation, and percentage participation of spikes in bursts revealed, however, that GPi neurons in HD patients fired in a more regular pattern (fewer "bursts") than in PD patients. These results suggest that the rate-based model does not adequately explain the motor abnormalities present in the two HD patients studied. Furthermore, the findings did reveal a difference between firing patterns in the HD and PD groups, thereby supporting the role of altered firing patterns in the pathophysiology of these diseases.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.PARKRELDIS.2019.11.004
Abstract: Dystonia is a clinically and genetically heterogeneous disorder and a genetic cause is often difficult to elucidate. This is the first study to use whole genome sequencing (WGS) to investigate dystonia in a large s le of affected in iduals. WGS was performed on 111 probands with heterogenous dystonia phenotypes. We performed analysis for coding and non-coding variants, copy number variants (CNVs), and structural variants (SVs). We assessed for an association between dystonia and 10 known dystonia risk variants. A genetic diagnosis was obtained for 11.7% (13/111) of in iduals. We found that a genetic diagnosis was more likely in those with an earlier age at onset, younger age at testing, and a combined dystonia phenotype. We identified pathogenic/likely-pathogenic variants in ADCY5 (n = 1), ATM (n = 1), GNAL (n = 2), GLB1 (n = 1), KMT2B (n = 2), PRKN (n = 2), PRRT2 (n = 1), SGCE (n = 2), and THAP1 (n = 1). CNVs were detected in 3 in iduals. We found an association between the known risk variant ARSG rs11655081 and dystonia (p = 0.003). A genetic diagnosis was found in 11.7% of in iduals with dystonia. The diagnostic yield was higher in those with an earlier age of onset, younger age at testing, and a combined dystonia phenotype. WGS may be particularly relevant for dystonia given that it allows for the detection of CNVs, which accounted for 23% of the genetically diagnosed cases.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.PARKRELDIS.2012.02.007
Abstract: Inter-rater reliability for the Toronto Western Spasmodic Torticollis Rating Scale has been determined for neurologists, but not for physiotherapists. We assessed the inter-rater reliability of scoring the clinical severity subscale of the Toronto Western Spasmodic Torticollis Rating Scale by two physiotherapists and two neurologists. Seven in iduals with cervical dystonia were assessed on video a total of 23 times. The assessments were randomized and rated by all raters. Reliability for all raters considered together, assessed by the Intraclass Correlation Coefficient (ICC 2,1) was 0.74 (p < 0.001, 95% CI 0.46-0.88). Reliability for the two clinician groups was not significantly different: neurologists ICC (2,1) = 0.75 (p < 0.001, 95% CI 0.44-0.89), physiotherapists ICC (2,1) = 0.82 (p < 0.001, 95% CI 0.30-0.94). The clinical severity subscale of the Toronto Western Spasmodic Torticollis Rating Scale can be assessed with good inter-rater reliability when physiotherapists and neurologists are represented in the same rater pool.
Publisher: SAGE Publications
Date: 17-08-2012
Abstract: To investigate the feasibility and effectiveness of an active exercise program for cervical dystonia. Pilot randomized controlled, single-blind trial of a 12-week intervention followed by a four-week follow-up period. Supervised physiotherapy and outcome measurement sessions were conducted in a hospital outpatient physiotherapy setting. Participants also performed exercises at home. Twenty participants with idiopathic cervical dystonia were randomized into an experimental ( n = 9) or control ( n = 11) group. Two participants from the experimental group and one from the control group dropped out. The experimental group undertook a semi-supervised active exercise program aimed at correcting the dystonic head position, plus relaxation. The control group performed relaxation only. Feasibility of the intervention was assessed by recording adherence, muscle soreness, and adverse events. The primary outcome measure was blinded analysis of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score. The active exercise program was feasible and safe, with participants in the experimental group completing 84% of prescribed training sessions in the 12-week intervention period. There were no adverse events in either group, while mild muscle soreness was reported by 66% of the experimental group. There was no significant difference between groups at post-test or follow-up. The difference between groups of −1.9 (95% confidence interval (CI) –9.0–5.2) on the TWSTRS demonstrates a trend towards greater improvement for the experimental group. Active exercise for people with cervical dystonia is feasible and can be completed with good adherence and no adverse effects.
Publisher: Wiley
Date: 04-10-2013
DOI: 10.1002/MDS.25693
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.CORTEX.2011.03.014
Abstract: The suppression of automatic prepotent behaviour in favour of more successful, more 'appropriate' behaviour is the primary function of the frontal lobe. Five frontal-subcortical circuits connect the frontal lobe to the basal ganglia and the thalamus. We report 17 patients with small lesions in the downstream structures of the frontal-subcortical circuits displaying severe dysexecutive behaviour. Positron emission tomography (PET) demonstrated hypometabolism of the frontal lobe in some of these patients. The literature on frontal lobe dysfunction after lesions in the basal ganglia and thalamus is discussed and the semiology of frontal lobe dysfunction in relation to the frontal-subcortical circuits is highlighted. Derived from our findings we suggest a disconnection syndrome of the frontal lobe caused by lesions in the downstream structures of the frontal-subcortical circuits.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.PARKRELDIS.2014.12.019
Abstract: We report a prospective, open label study of 24 h levodopa-carbidopa intestinal gel (LCIG) as treatment for levodopa "unresponsive" freezing of gait (FOG) associated with Parkinson's disease. 5 patients with disabling FOG, documented as being levodopa "unresponsive", were commenced on continuous 24 h infusion LCIG therapy with the night-time rate at 50-80% of the daytime infusion rate. Patients underwent baseline, 3 and 6 month gait assessments, documentation of their falls frequency and completed FOG questionnaires. Median 360° turn time improved by 54%, fall frequency score reduced from 3 to 0 at 6 months, FOG questionnaire score improved by 14% and Timed Up- and -Go 8 m walk was unchanged. 24 h LCIG therapy may reduce levodopa "unresponsive" FOG and associated falls. A larger prospective study is needed for confirmation.
Publisher: BMJ
Date: 05-2005
No related grants have been discovered for Neil Mahant.