Niemann Pick type C

Subcortical Morphology in Niemann Pick Type C

Striatal, hippocampal, thalamic and cerebellar MRI changes characterise NPC

In two recent papers, we have shown that Niemann-Pick type C (NPC) in adults is characterised by significant subcortical volumetric changes that correlate with various illness variables including cognition, ataxia and ocular-motor functioning. This expands on our suite of neuroimaging papers in NPC, the only group neuroimaging studies in this disorder, by further clarifying the relationships between brain changes and behaviour in this disorder. We have shown that volumetric changes are greatest in those regions that carry the largest neurofibrillary tangle burden and/or ganglioside excess based on neuropathological studies, and that these changes correlate with illness stage, cognition, ataxia measures and key ocular-motor saccadic measures. The first paper involved collaborating with Brian Patenaude (author of the FIRST toolbox in FSL, from the Oxford FMRIB group); the second utilised Freesurfer methodology to parcellate the cerebellum.

These two papers can be found
here and here.

Walterfang et al. Subcortical volumetric reductions in adult Niemann-Pick type C: a cross-sectional study.
Am J Neuroradiol in press.

Walterfang et al. Cerebellar volume correlates with saccadic gain and ataxia in adult Niemann-Pick type C.
Mol Genet Metab 108: 85-89, 2013.

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.

Pontine to midbrain ratio: useful in NPC

THE PONTINE TO MIDBRAIN RATIO: USEFUL IN NPC, TOO

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.