Movement Disorders Lab

Movement Disorder
Movement Disorders Lab group L- R:  Dr Lin Zhang, Prof. Dominic Thyagarajan, Dr Richard Blaze, Dr Will Lee, Dr Kelly Bertram (Group Lead) and Dr Salar Mcmodie

Key terms

Parkinson’s Disease, Movement Disorders, Atypical Parkinsonism, Dystonia, Tremor, Deep Brain Stimulation surgery

Research Goal

To improve diagnosis and treatment options for people living with Movement Disorders including Parkinson’s Disease, atypical Parkinsonism, and Dystonia.

Research Overview

Our research focusses on improving biomarkers for diagnosis of and clinical parameters affecting people living with Parkinson’s disease, Progressive Supranuclear Palsy, Multiple System Atrophy and Dystonia.

We are actively engaged in clinical trials bringing new treatment options to people with Parkinson’s disease, Parkinson’s disease dementia, Progressive supranuclear Palsy, Huntington’s disease and essential tremor. We lead the victorian component of the national Australian Parkinson’s Mission trial into medication repurposing aiming to find disease modifying agents for people living with Parkinson’s disease, and reseaching the genetics of medication response.

Investigator initiated research has included biomarker development for atypical parkinsonism including transcranial Magnetic Stimulation in Progressive Supranuclear Palsy and Multiple System Atrophy. We are also exploring potential links between Parkinson’s cognitive impairment and changes on TMS response.

Current Masters students / projects

Dr Lin Zhang
Supervisors: Dr Kelly Bertram, Dr Elspeth Hutton, Prof Terry O’Brien

Prevalence of Cervical Dystonia in subjects with Chronic Migraine

Cervical dystonia is characterised by abnormal head and neck postures, with pain reported in 70% of patients. The pathways involved in dystonia pathobiology interface with those involved in sensory processing, and sensory symptoms may be reported prior to motor ones. This is reflected in studies which have found a number of abnormalities in sensory testing measures in dystonia patients, including pressure pain threshold reduction, temporal and spatial discrimination abnormalities, and distorted body perception, reflected in mental rotation tasks (Stamelou, Edwards et al. 2012). The mechanisms are thought to involved reduced motor inhibition and altered brain plasticity. Migraine is a common cause of disability in our community ( Abajobir et al. 2017), and some cases can be refractory to treatment. Neck pain is a significant component of symptomatology for many patients with migraine, which may be refractory to physiotherapy and ergonomic modulatory measures. Clinical association between headache/migraine and cervical dystonia has been increasingly recognised in recent years however epidemiological and other studies exploring this association are lacking. This study is an investigator initiated multi-sites observational study on disease prevalence, aiming to explore this association.

Dr Andrew Ma
Supervisors: Prof Dominic Thyagarajan, Prof Terry O’Brien

Vocal Cord Hypokinesis As A Marker of Parkinson’s Disease Severity

Voice changes precede other motor features of Parkinson’s disease (PD) by 5 to 10 years [1] and affect up to 89% of those with idiopathic PD [2]. With a novel technique using dynamic 320-slice CT to quantitate vocal movements, we found that arytenoid cartilage movements are reduced during vocalisation in early PD [3]. On the other hand, glottic area is not reduced, supporting previous observations that the vocal folds are 'bowed' in this disease [4]. Other techniques demonstrating this phenomenon have relied on videolaryngoscopy, stroboscopy, assessment of laryngeal pressures and laryngeal electromyography [4-6], but their clinical application and practicality have thus far been limited. Our novel quantitative radiological technique as described in Perju-Dumbrava et al [3] has demonstrated that in those with early PD, vocal cord hypokinesia is reduced and that such changes correlate with clinically perceived changes in speech. This research aims to extend beyond this preliminary work by further assessing vocal cord movements across varying severities of PD.  The eventual application of this technique may be to the diagnosis and assessment of severity of PD.
This research aims to demonstrate that reduction in vocal fold movements as demonstrated on CT imaging, is positively correlated with the duration or clinical severity of Parkinson’s disease.

Current Project Funding

  • 2018 Bethlehem Griffiths Foundation Grant for project tentitled “Is deep brain stimulation neuroprotective in Parkinson’s disease?" CIs Joo Hyung Lee, D Thyagarajan $50,000
  • 2016 Bethlehem Griffiths Foundation Grant for project entitled "Preclinical validation of SRY as a therapeutic target for Parkinson's disease" CIs Joo Hyung Lee, D Thyagarajan and Vincent Harley,$50,000
  • 2016 Parkinson’s Victoria Atypical Parkinsonism community research award, Dr Kelly Bertram, Transcranial Magnetic Stimulation in Atypical Parkinsonism $30 000

Selected Recent Publications

For full list of publications visit Pubmed.

  1. McGuigan S, Zhou S, Brosnan M, Thyagarajan D, Bellgrove M, Chong T.Dopamine restores cognitive motivation in Parkinson’s disease. Brain. 2018
  2. Ding C, Palmer CJ, Hohwy J, Youssef GJ, Paton B, Tsuchiya N, Thyagarajan D et al. Deep Brain Stimulation for Parkinson’s disease changes perception in the Rubber Hand Illusion. Sci Rep. 2018 8(1):13842
  3. Lee W, Williams D, Evans A. Feasibility of Smartphone-based Testing of Interference in Parkinson’s Disease Neurodegener Dis. 2018;18(2-3):133-142.
  4. Lee YC, Williams DR, Anderson JFI. Prospective Characterization of Cognitive Function in Typical and 'Brainstem Predominant‘ Progressive Supranuclear Palsy Phenotypes.J Mov Disord. 2018;11(2):72-77.
  5. Morley JF, Cohen A, Silveira-Moriyama L, Lees AJ, Williams DR,et al.Optimizing olfactory testing for the diagnosis of Parkinson's disease: item analysis of the university of Pennsylvania smell identification test.NPJ Parkinsons Dis. 2018;15;4:2.
  6. Vijiaratnam N, Sirisena D, Paul E, Bertram KL, Williams DR. Measuring disease progression and disability in orthostatic tremor. Parkinsons and related disorders. 2018;55:138-140
  7. Vijiaratnam N, Williams DR, Bertram KL. Neck Pain: what if its not musculoskeletal? AJGP 2018;47(5) 168-171
  8. Vijiaratnam N, Hewer S, Ligtermoet M, Varley S, Eldho P, Lee W, Bertram KL, Williams DR levodopa-carbidopa intestinal gel: is the nasojejunalphase a redundant convention? Internal medical journal. 2018;48(4)469-471
  9. Bologna M,  Bertram KL,  Paparella G, Papi C, Belvisi D, Conte A, Suppa A, Williams DR, Berardelli A.  Reversal of long term potentiation-like plasticity in primary motor cortex in patients with progressive supranuclear Palsy. Clinical Neurophysiology 2017;128(9):1547-1552
  10. Vijiaratnam N , Bertram KL, Williams DR. Liquid levodopa/carbidopa: old solution, forgotton complication. Journal of Movement Disorders 2017;10(3):164-165
  11. Wasser CI, Evans F, Kempnich C, Glikmann-Johnston Y, Andrews SC, Thyagarajan D et al. Emotion Recognition in Parkinson’s Disease: Static and Dynamic Factors. Neuropsychology 2017.  doi:10.1037/neu0000400.
  12. Desai N, Rao AS, Palaniswami P, Thyagarajan D, Palaniswami M. Arytenoid cartilage feature point detection using laryngeal 3D CT images in Parkinson’s disease. Conf Proc Annu Int Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Annu Conf 2017; 2017: 1820–1823.
  13. Perju-Dumbrava L, Lau K, Phyland D, Papanikolaou V, Thyagarajan D et al. Arytenoid cartilage movements are hypokinetic in Parkinson’s disease: Aquantitative dynamic computerised tomographic study. PloS One 2017; 12:e0186611
  14. Lees AJ, Ferreira J, Rascol O, Poewe W, Williams, DR et al. Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA
  15. Lee W, Evans A, Williams DR. Subjective perception ofsleep benefit  in parkinson’s disease:Valid or irrelevant? Parkinsonism Rel Disord 2017;42:90-94
  16. Lee W, Evans AH, Williams DR. Objective Measurement and characterization of sleep benefit in Parkinson’s disease. Move Disord Clin Pract 2017;4(4):590-596
  17. Williams DR, Evans AH, Fung VCS, Hayes M, Iansek, R, Kimber T, O’Sulivan JD, Sue CM. Practical approaches to commencing device-assisted therapies for Parkinson disease in Australia. Intern Med J2017;47(10)1107-1113
  18. Ding C, Palmer CJ, Hohwy J,Thyagarajan D et al. Parkinson’s disease alters ultisensory perception: Insights from the Rubber Hand Illusion. Neuropsychologia 2017; 97: 38–45.
  19. Bertram, KL and Williams, DR. Delays to the diagnosis of cervical dystonia. Journal of Clinical Neuroscience 2016;25:62-4
  20. Bertram, KL and Colosimo, C. Camptocormia may be myopathic or dystonic. Muscle Nerve 2016;54(2):343
  21. Galimberti D, Bertram K, Formica A, Fenoglio C, Cioffi SM, Arighi A, Scarpini E, Colosimo C. Plasma screening for progranulin mutations in patients with progressive supranuclear palsy and corticobasal syndromes. J Alzheimers Dis. 2016; may 4;53(2):445-9
  22. Vijiaratnam N, Siresena D, Paul E, Bertram KL, Williams DR. Orthostatic tremor: Disease progression and disability [abstract]. Mov Disord. 2016; 31 (suppl 2).
  23. Quattrone A, Morelli M, Williams DR etal. MR parkinsonism index predicts vertical supranuclear gaze palsy in patients with PSP-parkinsonism. Neurology 2016;87(12):1266-73
  24. Hewer S, Varley S, Boxer AL, Paul E, Williams DR. Minimally clinically important worsening on the progressive supranuclear palsy rating scale.Mov Disord 2016;31(10):1574-77
  25. Lee W, Evans A, Williams, DR. Validation of a smartphone application measuring motor function in Parkinson’s disease. J Parkinsons Dis. 2016;6(2):371-82
  26. Lee YE, Williams DR, Anderson JF. Frontal deficits differentiate progressive supranuclear palsy from Parkinson’s diseases. J Neuropsychol 2016;10(1):1-4
  27. Cheshire P, Ayton S, Bertram KL, Ling H, Li A, McLean C, Halliday GM, O’Sullivan SS, Revesz T, Finkelstein DI, Storey E, Williams DR. Serotonergic markers in Parkinson’s disease and levodopa-induced dyskinesias. Movement Disorders 2015;30(6):796-804
  28. Cheshire, P; Bertram, K.; Ling, H.; O'Sullivan, S.; Halliday, G.; McLean, C.; Bras, J.; Foltynie, T.; Storey, E.; Williams, D. Influence of single nucleotide polymorphisms in COMT, MAO-A and BDNF genes on dyskinesias and levodopa use in Parkinson's disease, Neurodegenerative Diseases 2014;13(1):24-8