Publications
A/Professor Raymond Schwartz
PhD MBBS FRACP
Publications of A/Professor Raymond Schwartz
Neuroimaging Pearls from the MDS Congress Video Challenge. Part 2: Acquired Disorders
Fearon C, Rawal S, Olszewska D, … Schwartz RS, Fung VSC et al. Mov Disord Clin Pract. 2022;9(3):311–325.
A curated collection of challenging movement disorder cases drawn from the MDS Congress Video Challenge, focusing on acquired neurological conditions. Cases are paired with expert neuroimaging commentary to illustrate key diagnostic pearls. The series serves as an educational resource for clinicians interpreting complex movement presentations. A/Prof Schwartz contributed alongside an international faculty from the Movement Disorder Society.
Parkinsonism and Cerebrovascular Disease
Narasimhan M, Schwartz R, Halliday G. J Neurol Sci. 2022 Feb 15;433:120011.
This review examines the intersection of Parkinson’s disease and cerebrovascular pathology, exploring how small vessel disease and infarcts may contribute to or modify parkinsonian features. The authors discuss clinical, neuroimaging, and neuropathological evidence linking the two conditions. The paper is particularly relevant to understanding vascular parkinsonism and the limitations of clinical diagnosis in mixed pathology. It builds on A/Prof Schwartz’s longstanding research interest in the overlap between vascular and neurodegenerative disease.
Mills Syndrome: Clinical and Radiologic Asymmetry
Huynh W, Tu S, Mahoney CJ, Schwartz R, Kiernan MC. Neurology. 2021 Apr 6;96(14):677–678.
A focused clinical communication describing Mills Syndrome, a rare and controversial variant of motor neuron disease characterised by ascending hemiplegia. The report documents its hallmark asymmetrical clinical and radiological features on MRI, helping to differentiate it from more common motor neuron conditions. This case, involving collaboration across Southern Neurology and the University of Sydney’s neurology group, contributes to the very limited literature on this syndrome. It underscores the value of specialist neuroimaging in diagnostically atypical motor neuron presentations.
Teaching Video NeuroImage: Clenched Fists as an Unusual Presentation of Focal Neuromyotonia
Dhanapalaratnam R, Schwartz R, Huynh W. Neurology. 2021 Jul 27;97(4):e429–e430
This teaching case reports an atypical presentation of focal neuromyotonia manifesting as involuntary clenched fists, a clinical sign rarely described in the neuromyotonia literature. The accompanying video highlights the diagnostic value of careful observation and electrophysiological testing in distinguishing peripheral nerve hyperexcitability syndromes. The case emerged from Southern Neurology’s clinical practice and is co-authored by A/Prof Schwartz and A/Prof Huynh alongside Dr Dhanapalaratnam. It exemplifies the practice’s contribution of high-quality clinical teaching material to the neurology community.
Functional Outcomes of an Integrated Parkinson’s Disease Wellbeing Program
Horne JT, Soh D, Cordato DJ, Campbell ML, Schwartz RS. Australas J Ageing. 2020 Mar;39(1):e94–e102.
This prospective study evaluated the impact of a multidisciplinary, community-integrated Parkinson’s Disease Wellbeing Program on patient functional outcomes, including motor performance, quality of life, and mood. The program combined physiotherapy, occupational therapy, and nurse-led support in a co-ordinated outpatient model. Results demonstrated meaningful gains in patient-reported functional status and sustained engagement over the follow-up period. The study reflects Southern Neurology’s commitment to holistic, evidence-based care for patients with complex movement disorders.
Epidural Blood Patch as a Diagnostic and Therapeutic Intervention in Spontaneous Intracranial Hypotension
Davies MJ, Davies MA, Sharpe R, Cordato D, Schwartz R. World Neurosurg. 2020 May;137:e242–e250.
This paper describes a novel diagnostic and therapeutic approach to spontaneous intracranial hypotension (SIH), a condition caused by spontaneous CSF leakage, often difficult to localise with conventional imaging. The authors detail the use of epidural blood patching both to confirm the diagnosis and to provide durable clinical relief in a series of patients. The approach offers a practical framework for clinicians managing SIH in settings where advanced spinal imaging is inconclusive. The research highlights Southern Neurology’s expertise in managing complex CSF pressure disorders.
Real-World Effectiveness of OnabotulinumtoxinA for Prevention of Headaches in Chronic Migraine in Australia
Stark C, Stark R, Limberg N, … Cordato D, Schwartz R, Jukic R. J Headache Pain. 2019;20(1):81.
A retrospective real-world study assessing the effectiveness of onabotulinumtoxinA (Botox) for chronic migraine prevention in an Australian clinical cohort, providing locally relevant effectiveness data beyond randomised trial populations. The study found meaningful reductions in headache days and improved patient quality of life consistent with international evidence. It adds to growing literature supporting the routine use of botulinum toxin in treatment-refractory chronic migraine. The findings were particularly important for informing PBS access criteria discussions in Australia.
Impact of Small Vessel Disease on Severity of Motor and Cognitive Impairment in Parkinson’s Disease
Schwartz RS, Halliday GM, Soh D, Cordato DJ, Kril JJ. J Clin Neurosci. 2018 Dec;58:70–74.
This clinicopathological study investigated how the burden of cerebral small vessel disease (SVD) modifies the severity of motor and cognitive impairment in pathologically confirmed Parkinson’s disease. Analysis revealed that greater SVD burden was associated with worse cognitive outcomes, even after controlling for Lewy body pathology load. The findings suggest SVD is an independent contributor to disability in Parkinson’s disease, with implications for identifying patients at risk of accelerated cognitive decline. This work represents one of the few neuropathologically-grounded studies on this topic from an Australian centre.
Siponimod versus Placebo in Secondary Progressive Multiple Sclerosis (EXPAND): A Phase 3 Study
Kappos L, Bar-Or A, Cree BAC, … EXPAND Clinical Investigators. Lancet. 2018 Mar 31;391(10127):1263–1273.
The landmark EXPAND trial was the first Phase 3 study to demonstrate significant slowing of disability progression in secondary progressive multiple sclerosis (SPMS), a form of MS with limited effective treatment options. Siponimod, a selective S1P receptor modulator, reduced disability progression risk by 21% versus placebo over 24 months. The trial included contributions from Australian sites and was pivotal in establishing siponimod as a regulatory-approved therapy for SPMS. This publication in The Lancet represents one of the highest-profile MS trials in recent years.
Alemtuzumab Improves Preexisting Disability in Active Relapsing-Remitting MS Patients (CARE-MS II)
CARE-MS II Investigators. Neurology. 2016 Nov 8;87(19):1985–1992.
This analysis from the CARE-MS II trial examined whether alemtuzumab, a monoclonal antibody targeting CD52, could not only halt disease activity but actually reverse accumulated neurological disability in relapsing-remitting MS patients. The results demonstrated that a meaningful proportion of patients showed confirmed improvement in their Expanded Disability Status Scale (EDSS) scores, a finding rarely observed with other MS disease-modifying therapies. The paper strengthened the case for alemtuzumab as a high-efficacy, immunoreconstitution therapy. Australian site participation in the CARE-MS programme reflects the practice’s involvement in pivotal MS trials.
Biofeedback as a Psychological Intervention in Multiple Sclerosis: A Randomized Controlled Study
Mackay AM, Buckingham R, Schwartz RS, Hodgkinson S, Beran RG, Cordato DJ. Int J MS Care. 2015;17(3):101–8.
This randomised controlled trial tested whether biofeedback-based psychological intervention could improve psychological wellbeing and quality of life outcomes in multiple sclerosis patients. The intervention addressed stress, mood dysregulation, and fatigue — symptoms often underserved by pharmacological MS management. The trial, conducted through the St George/Southern Neurology group, found significant benefits in self-reported wellbeing measures for the biofeedback arm. It represents an important contribution to non-pharmacological approaches to MS symptom management.
Rebound Exacerbation in Multiple Sclerosis Following Cessation of Oral Treatment
Beran RG, Hegazi Y, Schwartz RS, Cordato DJ. Mult Scler Relat Disord. 2013 Jul;2(3):252–5.
This case-based report documented significant rebound MS disease activity following abrupt cessation of an oral disease-modifying therapy, highlighting the clinical risks of therapy discontinuation without appropriate transition planning. At the time of publication, rebound activity was an emerging safety concern as novel oral MS agents gained clinical uptake. The paper contributed early Australian clinical data to this important safety literature. It carries ongoing relevance for neurologists managing treatment transitions in relapsing MS.
Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis (DEFINE)
Gold R, Kappos L, Arnold DL, … DEFINE Study Investigators. N Engl J Med. 2012 Sep 20;367(12):1098–107.
The DEFINE trial established the efficacy of dimethyl fumarate (BG-12, subsequently Tecfidera) in relapsing MS, demonstrating approximately 49% reduction in annualised relapse rate versus placebo over two years. This was one of two pivotal Phase 3 trials that led to global regulatory approval of dimethyl fumarate as an oral first-line MS therapy. Published in the New England Journal of Medicine, DEFINE remains one of the most cited MS trials of the modern era. Australian site participation underscores Southern Neurology’s involvement in landmark global CNS trials.
Small-Vessel Disease in Patients with Parkinson’s Disease: A Clinicopathological Study
Schwartz RS, Halliday GM, Cordato DJ, Kril JJ. Mov Disord. 2012 Oct;27(12):1506–12.
One of the earlier foundational papers from A/Prof Schwartz’s research programme, this study used post-mortem neuropathological assessment to systematically quantify the co-occurrence of small vessel cerebrovascular disease in Parkinson’s disease brains. The work demonstrated that SVD is common in PD and correlates with clinical features such as gait impairment and dementia. Published in Movement Disorders, it was among the first clinicopathological studies to rigorously address this dual pathology in an Australian cohort. The findings informed subsequent clinical research into vascular contributions to parkinsonism.
Alemtuzumab for Patients with Relapsing MS after Disease-Modifying Therapy (CARE-MS II)
Coles AJ, Twyman CL, Arnold DL, … CARE-MS II investigators. Lancet. 2012 Nov 24;380(9856):1829–39.
The CARE-MS II Phase 3 trial directly compared alemtuzumab to subcutaneous interferon beta-1a in relapsing-remitting MS patients who had experienced disease activity on prior therapy. Alemtuzumab demonstrated superior reduction in relapse rates and disability worsening, establishing it as a high-efficacy option for active or breakthrough MS. Published in The Lancet, CARE-MS II was pivotal in securing regulatory approvals globally. The trial’s long-term extension data have since further reinforced the durable benefit of the alemtuzumab immunoreconstitution approach.
Health-Care Costs in Parkinson’s Disease vs Non-PD Patients in Southern Sydney
Cordato DJ, Schwartz R, Abbott E, Saunders R, Morfis L. J Clin Neurosci. 2006 Jul;13(6):655–8.
This health economics study compared direct medical costs for Parkinson’s disease patients and matched controls in the Southern Sydney healthcare region, providing an early Australian estimate of the cost burden attributable to PD. Hospital admissions, medication costs, and allied health utilisation were all significantly higher in the PD cohort. The findings helped contextualise the economic case for early specialist intervention and disease management programs. This remains one of the few region-specific PD cost studies published from Australia.
Dementia in Non-Paraneoplastic Limbic Encephalitis Associated with Relapsing Polychondritis
Yan M, Cooper W, Harper C, Schwartz R. Pathology. 2006 Dec;38(6):596–9.
This case report describes a rare association between relapsing polychondritis — an inflammatory cartilage condition — and non-paraneoplastic limbic encephalitis presenting with progressive dementia. The neuropathological findings are described in detail, offering insight into the neuro-immune mechanisms underlying this unusual syndrome. The case adds to the very limited literature on CNS involvement in relapsing polychondritis and illustrates the importance of multisystem assessment in unexplained dementia. Pathological confirmation strengthens the clinical and mechanistic significance of this rare observation.
Evoked Potentials in the Femoral Cutaneous Nerves in Meralgia Paresthetica
Cordato DJ, Yiannikas C, Stroud J, Halpern JP, Schwartz RS, Akbunar M, Cook M. Muscle Nerve. 2004;29(1):139–42.
This electrophysiological study described a technique for recording evoked potentials from the lateral and anterior femoral cutaneous nerves to objectively diagnose meralgia paresthetica, a common but often clinically under-recognised nerve entrapment syndrome. The methods proposed provided an electrodiagnostic complement to clinical assessment, improving diagnostic precision in a condition where conventional nerve conduction studies are technically unreliable. Published in Muscle & Nerve, this remains a useful reference for neurophysiologists evaluating patients with anterior thigh sensory symptoms.
Positional Vomiting Due to a Thoracic Spinal Dural Arteriovenous Fistula
Cordato DJ, Davies MA, Masters LT, Cremer PD, Schwartz RS, Sorby W, Becvarovski Z. J Neurosurg Spine. 2004;1(2):219–22.
This neurosurgical case report describes an unusual presentation of a thoracic spinal dural arteriovenous fistula (DAVF) manifesting primarily as positional vomiting — a symptom typically attributable to posterior fossa or vestibular pathology rather than thoracic spinal vascular disease. The case illustrates the diagnostic challenges posed by atypical DAVF presentations and the importance of spinal vascular imaging in unexplained progressive myelopathy. Multidisciplinary input from neurologists, neurosurgeons, and neuroradiologists was required for diagnosis and successful management. This remains a valuable teaching case in spinal vascular neurology.
A/Professor Dennis Cordato
PhD MBBS FRACP
Selected Publications 2020-2022 of A/Professor Dennis Cordato
Clinical Outcomes Following Reperfusion Therapy in Acute Ischemic Stroke with Infective Endocarditis
Maheshwari R, Cordato D, Wardman D, Thomas P, Bhaskar S. J Cent Nerv Syst Dis. 2022;14:11795735221081597.
This systematic review examined outcomes in an uncommon but challenging clinical scenario: patients with infective endocarditis presenting with acute ischemic stroke who receive intravenous thrombolysis or endovascular thrombectomy. Concerns about haemorrhagic transformation and embolic recurrence have traditionally deterred reperfusion therapy in this group. The review synthesises available evidence to help guide decision-making in this high-risk population. It contributes to an area where clinical guidelines remain incompletely informed by evidence.
Cerebrovascular Disease Profiles in Pacific Islander vs Caucasian Stroke Patients
Blair C, Firtko A, Edwards L, … Cordato DJ. Neuroepidemiology. 2022;56:25–31.
This multicentre study compared stroke risk factor profiles and clinical characteristics between Pacific Islander and Caucasian patients presenting to South-Western Sydney hospitals with acute stroke or transient ischaemic attack. Pacific Islander patients were younger and had a higher burden of modifiable risk factors including diabetes and hypertension. The findings highlight important ethnic disparities in cerebrovascular disease presentation and underscore the need for culturally tailored stroke prevention strategies. A/Prof Cordato’s group has been a national leader in studying stroke in culturally and linguistically diverse populations.
Creutzfeldt-Jakob Disease in South Western Sydney 2014–2016
Goire N, Edwards L, Thomas P, Bhaskar SMM, Cordato D, Buckland M, Beran RG. Neuroepidemiology. 2022;56:59–65.
This regional epidemiological study characterised confirmed cases of Creutzfeldt-Jakob Disease (CJD) presenting across South Western Sydney over a two-year period, examining clinical features, diagnostic pathways, and survival outcomes. The study provides rare Australian regional surveillance data on this rapidly progressive prion disease. Neuropathological confirmation was available for a substantial proportion of cases, allowing for clinicopathological correlation. The paper informs local clinical awareness and supports the broader CJD surveillance network in Australia.
The Auditory Afferent Pathway as a Clinical Marker of Alzheimer’s Disease
Shad KF, Soubra W, Cordato DJ. J Alzheimer’s Dis. 2022;85(1):45–73.
This comprehensive review examines the evidence that dysfunction of the central auditory pathways may serve as an early and accessible biomarker for Alzheimer’s disease, potentially detectable before overt cognitive decline. The authors evaluate neuroanatomical, electrophysiological, and clinical data linking auditory processing abnormalities to AD pathology. The pathway offers a non-invasive window into cortico-limbic degeneration that may prove clinically useful in pre-dementia populations. The review positions auditory testing as a candidate screening tool for enriching Alzheimer’s disease prevention trials.
Advanced Care Directives in an Australian Motor Neuron Disease Multidisciplinary Clinic
Phua CS, Ng A, Brooks C, … Cordato D. Postgrad Med J. 2021;97:566–570.
This study assessed the prevalence and determinants of Advanced Care Directive (ACD) completion in patients attending a multidisciplinary MND clinic in Australia, finding that ACDs remained underutilised despite the progressive and terminal nature of the disease. Factors associated with ACD completion included older age, longer disease duration, and higher level of disability. The findings highlight an important gap in end-of-life planning for MND patients and point to opportunities for systematic advance care planning integration into multidisciplinary clinic workflows. The paper has direct relevance for palliative care planning in neurodegenerative disease.
Effect of IV Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy (EXTEND-IA TNK Part 2)
Campbell BCV, Mitchell PJ, Churilov L, … Cordato D, … EXTEND-IA TNK Part 2 investigators. JAMA. 2020;323(13):e200015.
This randomised clinical trial compared standard dose versus higher dose tenecteplase as a bridging thrombolytic agent prior to endovascular thrombectomy in large vessel occlusion ischaemic stroke, seeking to optimise pre-procedural reperfusion rates. The results demonstrated that 0.25 mg/kg tenecteplase achieved superior angiographic reperfusion outcomes compared to the lower 0.1 mg/kg dose. Published in JAMA, EXTEND-IA TNK Part 2 was pivotal in establishing the preferred tenecteplase dose in the thrombectomy-eligible stroke population. Australian centres including A/Prof Cordato’s network played a central role in this important trial.
DIRECT-SAFE: Endovascular Thrombectomy vs Bridging Thrombolysis within 4.5 Hours
Mitchell PJ, Yan B, Churilov L, … Cordato D, … DIRECT-SAFE investigators. Lancet. 2022.
DIRECT-SAFE was a multicentre Asia-Pacific randomised controlled trial comparing direct endovascular thrombectomy versus standard bridging intravenous thrombolysis followed by thrombectomy in the 4.5-hour treatment window for large vessel occlusion stroke. The trial addressed the ongoing clinical equipoise around whether bridging thrombolysis adds benefit over thrombectomy alone. Published in The Lancet, this is one of the most significant stroke intervention trials in the Asia-Pacific region. A/Prof Cordato contributed as a site investigator to this landmark study.
A/Professor William Huynh
PhD BSc MBBS (Hons) FRACP · Over 70 Journal Publications
Publications & Textbook Chapters of A/Professor William Huynh
Neurorehabilitation Approaches for Disorders of the Peripheral Nervous System
Huynh W, Lee M, Kiernan MC. In: Oxford Textbook of Neurorehabilitation. OUP. 1st ed 2015; 2nd ed 2020.
A comprehensive chapter in the Oxford Textbook of Neurorehabilitation covering evidence-based rehabilitation strategies for peripheral nerve disorders, including Guillain-Barré syndrome, hereditary neuropathies, and acquired neuropathies. The chapter addresses functional recovery principles, electrophysiological monitoring during rehabilitation, and multidisciplinary management strategies. Updated for the second edition, the chapter reflects advances in neurorehabilitation science over the intervening five years. It serves as a key reference for clinicians and trainees managing patients with peripheral nerve and neuromuscular conditions.
Motor Neuron Disease (Balance, Gait, and Falls)
Dharmadasa T, Huynh W, Matamala JM, Zoing M, Kiernan MC. In: Day BL, Lord SR (Eds). Balance, Gait, and Falls. Elsevier, 2018.
This book chapter addresses the specific challenges of gait, balance impairment, and falls risk in motor neuron disease, a topic with significant implications for patient safety and quality of life. The authors review upper and lower motor neuron contributions to gait dysfunction and discuss the limited evidence base for rehabilitation interventions in ALS. Fall prevention and adaptive equipment strategies are addressed within the progressive disability trajectory of MND. The chapter remains an important clinical reference for neurologists, physiotherapists, and allied health professionals working with MND patients.
Selected Journal Publications — Recent to Earlier
Cortical Excitability Stratifies Neurochemical Profiles in ALS
Tu S, Mahoney CJ, Huynh W, Vucic S, Kiernan MC. Brain Communications. Accepted April 2026.
This study used transcranial magnetic stimulation to assess cortical excitability across ALS patients and then correlated these profiles with neurochemical signatures derived from magnetic resonance spectroscopy. The results indicate that cortical hyperexcitability — a well-established feature of ALS — correlates with distinct metabolic signatures, potentially enabling patient stratification for future clinical trials. The work advances the field’s understanding of how motor cortex dysfunction maps onto neurochemical pathology in ALS. Accepted in Brain Communications, it represents the latest contribution from A/Prof Huynh’s research programme.
Domain-Specific Cognitive Screening in Acute First-Ever Stroke: OCS vs ACE-III
Tanglay O, Jhunjhnuwala D, Huynh W. Front Hum Neurosci. 2026 Jan 12;19:1678230.
This comparative study evaluated the Oxford Cognitive Screen (OCS) and the Addenbrooke’s Cognitive Examination-III (ACE-III) in the acute stroke setting, assessing their relative sensitivity and specificity for domain-specific cognitive deficits such as aphasia, neglect, and memory impairment. The OCS was designed specifically for stroke-related cognitive profiles and demonstrated advantages in capturing domain-specific deficits that the ACE-III may miss in acute presentations. The findings have direct implications for clinical stroke unit practice, where rapid and sensitive cognitive assessment is essential for rehabilitation planning and discharge decisions.
Behavioral Subtypes Impact Prognosis and Survival in ALS
Tse NY, Caga J, Ahmed RM, … Huynh W, … Devenney EM. Amyotroph Lateral Scler Frontotemporal Degener. 2025;26(7-8):729–738.
This study applied unsupervised clustering to identify distinct behavioural subtypes within the ALS population and examined how these subtypes relate to survival and disease progression. Recognising that behavioural symptoms — including apathy, disinhibition, and emotional dysregulation — are common in ALS-FTD spectrum disorders, the study establishes that behavioural phenotyping has prognostic value beyond motor staging alone. The findings argue for routine behavioural assessment in ALS clinical trials and care settings. A/Prof Huynh’s contribution reflects his sustained research focus on the cognitive and behavioural dimensions of motor neuron disease.
Quantifying Neurodegeneration in Core Motor Pathways in ALS Using Diffusion MRI
Almgren H, Mahoney CJ, Huynh W, … Calamante F, Tu S. J Neurol. 2025;272(3):215.
This advanced neuroimaging study used diffusion MRI to quantify the degree and spatial pattern of white matter degeneration within the corticospinal tract and other primary motor pathways in ALS patients. The methodology allowed subdivision of tract degeneration beyond conventional tractography, providing finer-grained staging of structural neurodegeneration. The work contributes to a growing body of imaging biomarker research aimed at tracking disease progression and measuring treatment response in ALS clinical trials. A/Prof Huynh and Dr Mahoney are listed as key collaborators alongside the Brain and Mind Centre neuroimaging group.
Cerebrotendinous Xanthomatosis: A Clinically and Genetically Heterogeneous Condition
O’Keefe E, Kiernan M, Huynh W. Eur J Neurol. 2025;32(1):e70006.
This review characterises cerebrotendinous xanthomatosis (CTX), a rare but treatable autosomal recessive lipid storage disorder caused by CYP27A1 mutations, often misdiagnosed as progressive cerebellar ataxia or demyelinating disease. The authors document the broad clinical and genetic heterogeneity of CTX, emphasising that early diagnosis is critical given the availability of effective chenodeoxycholic acid replacement therapy. The review surveys the literature to inform neurologists of the clinical red flags that should prompt CTX testing in patients with unexplained progressive neurological disease. This represents an important educational contribution given the frequent diagnostic delay in CTX.
Efficacy and Safety of CNM-Au8 in ALS (RESCUE-ALS): A Phase 2 Randomised Trial
Vucic S, Menon P, Huynh W, Mahoney C, … Kiernan MC. EClinicalMedicine. 2023;60:102036.
RESCUE-ALS was a Phase 2 randomised, double-blind, placebo-controlled trial evaluating CNM-Au8, a gold nanocrystal compound designed to support neuronal bioenergetics, in early symptomatic ALS patients. The trial, in which A/Prof Huynh and Dr Mahoney served as investigators, assessed safety, tolerability, and biomarker outcomes including neurophysiological and metabolic markers. Published in EClinicalMedicine, RESCUE-ALS represents a novel mechanistic approach in ALS — targeting energy metabolism rather than excitotoxicity or protein aggregation. An open-label extension followed the double-blind phase, with long-term results under analysis.
Factors Influencing Non-Motor Impairment Across the ALS-FTD Spectrum
Devenney EM, McErlean K, Tse NY, … Huynh W, Mahoney CJ, … Kiernan MC. Front Neurol. 2021 Nov 25.
This large cohort study examined the impact of phenotype, sex, age, disease onset site, and disease stage on non-motor symptoms — including cognitive impairment, behavioural change, and emotional dysfunction — across the ALS-FTD spectrum. The analysis revealed that non-motor features are strongly influenced by phenotype subtype and disease stage, with bulbar-onset patients showing earlier and more severe cognitive involvement. These findings argue for phenotype-specific cognitive monitoring protocols and targeted non-motor outcome measures in ALS clinical trials. A/Prof Huynh and Dr Mahoney contributed to this multicentre Australian study.
Improving Clinical Trial Outcomes in Amyotrophic Lateral Sclerosis
Kiernan MC, Vucic S, Talbot K, … Huynh W, … Turner MR. Nat Rev Neurol. 2021;17(2):104–118.
Published in Nature Reviews Neurology, this authoritative review by leading international ALS researchers — including A/Prof Huynh — addressed the systematic challenges that have plagued ALS clinical trials, including phenotypic heterogeneity, imprecise eligibility criteria, and insufficient early-phase biomarker development. The paper proposed a framework for next-generation ALS trial design incorporating stratification by upper and lower motor neuron involvement, neurophysiological biomarkers, and digital health technologies. It has become one of the most influential methodological papers in modern ALS research and has shaped the design of recent Phase 2 and 3 trials globally.
The Impact of Cognitive and Behavioral Impairment in ALS
Huynh W, Ahmed R, Mahoney C, … Kiernan MC. Expert Rev Neurother. 2020.
This expert review systematically examined how cognitive impairment and behavioural change — occurring in up to 50% of ALS patients — affect disease management, caregiver burden, quality of life, and clinical trial participation. The paper reviewed the neuropsychological instruments available for detecting and tracking cognitive change in ALS, noting significant variability in sensitivity across tools. It also explored the biological basis of cognitive involvement in ALS, including frontotemporal network degeneration, and discussed implications for patient counselling and advance care planning. The review has become a standard reference for clinicians managing the broader ALS-FTD spectrum.
Functional Biomarkers for Amyotrophic Lateral Sclerosis
Huynh W, Dharmadasa T, Vucic S, Kiernan MC. Front Neurol. 2019;9:1141.
This review assessed the landscape of functional biomarkers — including neurophysiological, imaging, and biochemical measures — that can track disease progression and serve as surrogate endpoints in ALS trials. Threshold-tracking TMS-derived cortical excitability measures, electrical impedance myography, and phosphorylated neurofilament heavy chain are among the biomarkers reviewed and appraised for their practical utility. The paper argues that a multimodal biomarker strategy is necessary given the heterogeneity of ALS, and proposes a framework for integrating these tools into clinical trial design. It remains highly cited in the ALS biomarker literature.
Assessment of the Upper Motor Neurone in Amyotrophic Lateral Sclerosis
Huynh W, Simon NG, Groessler J, Turner M, Vucic S, Kiernan MC. Clin Neurophysiol. 2016;127(7):2643–60.
This detailed methodological review assessed the range of neurophysiological techniques available for the objective detection of upper motor neuron dysfunction in ALS — a major diagnostic challenge given the absence of a reliable biomarker. Threshold-tracking transcranial magnetic stimulation, cortical silent period measurement, and paired-pulse TMS protocols are each evaluated for diagnostic accuracy, reproducibility, and clinical applicability. The paper provides a practical guide for neurophysiologists and is particularly relevant for ALS diagnostic work-up and clinical trial eligibility assessment. It represents one of A/Prof Huynh’s most comprehensive methodological contributions.
Exploring the Evolution of Cortical Excitability after Stroke
Huynh W, Vucic S, Krishnan AV, Lin CS-Y, Kiernan MC. Neurorehabil Neural Repair. 2016;30(3):244–57.
This longitudinal study used threshold-tracking TMS to characterise the evolution of cortical excitability changes in stroke patients over the subacute to chronic recovery period. The authors found dynamic excitability changes — including early cortical depression followed by maladaptive hyperexcitability — that correlated with functional recovery trajectories. The findings have implications for the optimal timing of neuromodulatory interventions such as TMS-based rehabilitation. This work established A/Prof Huynh’s early research profile in the application of cortical excitability tools across both stroke and neurodegenerative disease.
Botulinum Toxin Modulates Cortical Maladaptation in Post-Stroke Spasticity
Huynh W, Krishnan AV, Lin CS-Y, Vucic S, Katrak P, Hornberger M, Kiernan MC. Muscle Nerve. 2012;48(1):93–9.
This study demonstrated that botulinum toxin injections for post-stroke spasticity not only reduce muscle tone peripherally but also modulate maladaptive cortical reorganisation in the ipsilesional motor cortex, as measured by threshold-tracking TMS. The cortical excitability changes following botulinum toxin correlated with improvements in clinical spasticity scores, suggesting a central mechanism of action beyond the neuromuscular junction. These findings were among the first to characterise the cortical effects of botulinum toxin in stroke patients and opened a new research direction in neurorehabilitation. The study was published in Muscle & Nerve during A/Prof Huynh’s doctoral research.
Post-Vaccination Encephalomyelitis: Illustrative Case and Literature Review
Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C. J Clin Neurosci. 2008;15:1315–1322. [Invited Review]
Published as an invited review early in A/Prof Huynh’s career, this paper presented a case of acute disseminated encephalomyelitis (ADEM) following vaccination and systematically reviewed the published literature on post-vaccination encephalomyelitis. The review addressed pathogenic mechanisms, clinical features, diagnostic criteria, and treatment approaches including corticosteroids and plasma exchange. It remains a widely cited reference for neurologists managing post-vaccination neuroimmunological complications, a topic of sustained clinical relevance. The paper was produced in collaboration with A/Prof Cordato’s group at Southern Neurology and St George Hospital.
Dr Colin Mahoney
PhD MBBCh MRCPI FRACP
Publication list coming soon.
Dr Christopher Blair
PhD MBBCh MRCPI FRACP
Publication list coming soon.
Dr Roshan Dhanapalaratnam
MBBS MMed FRACP
Publication list coming soon.
Dr Ying Liu
MBBS BOptom (Hons) FRACP