Movement Disorders

Neuropsychiatry of Movement Disorders

The unit’s 2013 Neuroimaging Fellow, Dr Brad Hayhow, has published an illustrated summary of how typical movement disorders associated with chorea, dystonia and ataxia are associated with neuropsychiatric illness. This review paper has been published in the new Columbia University movement disorders journal, Tremor.
The paper can be viewed in full here, and contains high-quality illustrations about frontal-subcortical circuits whose disruption can lead to psychiatric illness. One of the images can be found below.

Pasted Graphic
Prototypical frontostriatal circuit.

New Diagnostic Tool and Treatment Recommendations for NPC

New Diagnostic Tool and Treatment Recommendations for NPC

As part of the international NPC Guidelines working group, A/Prof Mark Walterfang has been involved in two new publications summarising the state-of-the-art in diagnosis and management of Niemann-Pick type C (NPC) disease. The first describes a “suspicion index” to assist clinicians in detecting patients who may have NPC, and allows for the ranking of symptoms to produce an overall illness score and then suggests pathways to diagnosis. The second is a thorough review and update regarding current diagnostic and management issues for clinicians treating patients with NPC, including multidisciplinary management, experimental treatments, and illness monitoring.

These two papers can be found
here and here.

Wijburg et al.
Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C. Neurology 78: 1560-1567, 2012.

Patterson et al. Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update.
Mol Genet Metab 106: 330-344, 2012.

Subcortial Morphology as a Dementia Biomarker


In collaboration with A/Prof Jeff Looi from the Australian National University, we have conducted a group of studies in various neurodegenerative disorders, and have shown that differing types of illness have relatively unique “shape signatures” that characterise their underlying pathology. These signatures may prove to be unique biomarkers for illness stage, progression over time and response to future illness-modifying therapies.

The two publications characterising these morphological changes in dementia can be found
here and here.

Looi et al. Striatal morphology as a biomarker in neurodegenerative disease.
Mol Psychiatry 2012 May 15. doi: 10.1038/mp.2012.54.

Looi et al.
Frontotemporal dementia as a frontostriatal disorder: neostriatal morphology as a biomarker and structural basis for an endophenotype. Aust NZ J Psychiatry 46: 422-434, 2012.

Pontine to midbrain ratio: useful in NPC


Niemann-Pick type C (NPC) disease is a rare autosomal recessive disorder that presents in adults with cognitive and motor disturbance, psychosis, and highly prominent vertical gaze palsy. We aimed to see if a validated measure in other disorders that demonstrate midbrain atrophy and have vertical gaze impairments was also useful in NPC. By examining a group of adult NPC patients and a larger group of matched controls, we showed that the pontine to midbrain ratio (PMR) - which, when elevated, reflects midbrain atrophy and consequent impairment of saccadic burst neurons that control eye gaze. We showed that this ratio is increased in NPC, although not to the same degree seen in other disorders such as progressive supranuclear palsy. However, this ratio was highly correlated to duration of illness and a range of measures of illness severity, including cognitive and ocular-motor functioning. The PMR may thus be a useful diagnostic and illness marker in NPC.

The paper can be found here.
Walterfang et al.
Pontine-to-midbrain ratio indexes ocular-motor function and illness stage in adult Niemann–Pick disease type C. Eur J Neurol, in press 2011.

Brain Changes in Adult NPC

Utilising methodology developed by Professor David Reutens, now at the Queensland Brian Institute, Dr Amanda Wood, from the University of Birmingham, and Drs Larry Abel and Elizabeth Bowman from the University of Melbourne’s Department of Optometry and Vision Sciences, we followed up our landmark MRI study in adults with Niemann-Pick disease type C (NPC) with a shape analysis of the corpus callosum (CC), the brain’s largest white matter fibre bundle, which connects the brain’s two hemispheres. This study demonstrated that the CC in NPC is globally thinned, but disproportionately thinned in regions similar to those seen in established schizophrenia, and may go some way to explaining the increased rate of psychosis in adults with NPC.

This paper can be found here.
Walterfang et al. Size and shape of the corpus callosum in adult Niemann-Pick type C reflects state and trait illness variables. American Journal of Neuroradiology 32: 1340-1346, 2011.