22. 15 years of niemann pick c in australia

20. Systematic review of the effect of coffee on parkinson diseaseriskMohammed T. Hasan a, Mellina Gattellari a, Dennis Cordato b

a University of New South Wales, NSWb Liverpool Hospital, NSW

Background: Previous research has demonstrated a protectiveeffect of coffee intake on the risk of developing Parkinson’s Disease(PD).

Objectives: To systematically review and critically appraise pub-lished evidence examining the effect of coffee consumption on therisk of developing PD.

Methods: We identified eligible English language cohort andcase-control studies from Medline and Embase data-bases (1950and 1980 to June 4, 2009, respectively) and assessed studies for qual-ity using the Newcastle-Ottawa Checklist. Data extraction was car-ried out independently by two reviewers before results weremeta-analysed using Review Manager 5.0.

Results: Seven cohort studies involving 248,511 participants and18 case-control studies with 14,345 participants met eligibility crite-ria for inclusion. Only one case-control study and one cohort studymet all quality assessment criteria. Results from six cohort and 16case-control studies were included in the meta-analysis. The pooledRelative Risk from these studies demonstrated a protective effect ofcoffee drinking (RR = 0.68; 95% CI 0.59–0.77). The protective effectappeared stronger in males (RR = 0.60; 95% CI 0.51–0.69) when com-pared with females (RR = 0.78; 95% CI 0.65–0.93). Significant heter-ogeneity existed in results from case-control but not cohortstudies. There was evidence of publication bias when comparingstudies published before and after 2002 (Chi2 = 3.78 (P = 0.05)).

Conclusions: This systematic review confirmed an inverse rela-tionship between coffee intake and PD, suggesting that caffeinemay be neuroprotective. However, publication bias and confoundingmay have influenced results.

Limitations: Unpublished literature was not systematically iden-tified. Reliance on unadjusted estimates may have biased results.

doi:10.1016/j.jocn.2010.07.021

21. Alterations to white matter microstructure and grey mattervolume in adult Niemann-Pick Type CMark Walterfang a, Michael C. Fahey b, Patricia Desmond c, AmandaG. Wood d, Marc Seal e, Michael Fietz f, Christopher Adamson g,Dennis Velakoulis a

a Neuropsychiatry Unit, Royal Melbourne Hospital, VICb Department of Paediatrics, Monash University, VICc Department of Radiology, Royal Melbourne Hospital, VICd Murdoch Children’s Research Institute, Royal Children’s Hospital, VICe Melbourne Neuropsychiatry Centre, University of Melbourne, VICf Department of Chemical Pathology, Women’s and Children’s Hospital,SAg Murdoch Children’s Research Institute, Royal Children’s Hospital, VIC

Objective: Niemann-Pick type C (NPC) disease is a progressiveneurovisceral disorder with disrupted intracellular cholesterolmetabolism, that results in significant alterations to neuronal andaxonal structure. Adult patients present with ataxia, gaze palsy,impaired cognition and neuropsychiatric illness, but the neural sub-strate has not been well-characterized in vivo. Our aim was to inves-tigate a well-characterized sample of adults with confirmed NPC forgrey and white matter abnormalities.

Methods: We utilized a combination of optimized voxel-basedmorphometry (VBM) of T1-weighted images and tract-based spatialstatistics (TBSS) of diffusion-tensor images (DTI) to examine greymatter volume and white matter structural differences in six adultNPC patients and eighteen gender- and age-matched controls.

Results: NPC patients demonstrated bilateral grey matter reduc-tions in large clusters in bilateral hippocampus, thalamus, superiorcerebellum and insula, in addition to smaller regions of inferoposte-rior cortex. Patients demonstrated widespread reductions in frac-tional anisotropy in major white matter tracts. Subsequent analysisof measures of axial and radial diffusivity suggest that these changesare contributed to by both impaired myelination and altered axonalstructure.

Conclusions: Findings in grey matter areas are broadly consistentwith human and animal studies of selective vulnerability of neuronalpopulations to the neuropathology of NPC, whereas more wide-spread white matter changes are consistent with the hypothesis thatdisrupted myelination and axonal structure predate changes to theneuronal cell body. These findings suggest that volumetric analysisof grey matter and diffusion tensor imaging may be useful modali-ties for indexing illness stage, and monitoring response to emergingtreatment.

doi:10.1016/j.jocn.2010.07.022

22. 15 years of Niemann Pick C in AustraliaMichael Fahey a, Drago Bratkovic b, Michael Fietz b,Dennis Velakoulis d, Elsdon Storey c, Mark Walterfang d

a Monash Medial Centre, VICb Women’s and Children’s Hospital, SAc Alfred Hospital, VICd Royal Melbourne Hospital, VIC

Niemann-Pick type C (NPC) disease is a rare progressive neurovis-ceral disorder with disrupted intracellular cholesterol metabolism,which results in significant alterations to neuronal and axonal struc-ture. While childhood onset disease results in severe liver disease,adolescent and adult patients may present with a range of symptomsincluding ataxia, gaze palsy, impaired cognition and neuropsychiat-ric illness.

Objective: To describe the history, clinical presentation, diagnosisand course of a group of patients diagnosed with Niemann Pick Cfrom Australia in the last 15 years.

Methods: Patients ascertained from a specialist neurogeneticsclinic, a dedicated neuropsychiatric unit and the Australian referencelaboratory are described. Diagnosis in all cases was confirmed withfilipin staining of cultured skin fibroblasts and cholesterol esterifica-tion rates. Genetic mutations were identified in many.

Results: Between 1995–2009, 40 cases, of NPC were diagnosed.Of these 22 were diagnosed after 5 years old and 15 after the ageof 12 and up to the fourth decade. Since symptom onset, manyhad been followed for years without diagnosis. As expected gastroin-testinal symptoms were prominent in those diagnosed early infancy.In the others, gaze paresis was a significant clue, although in theolder patients behavioural change and psychiatric symptoms werealso prominent. Clinical summaries and signs will be presented.

Conclusions: The presentation Niemann Pick C varies with differ-ent age groups clinical features, including gaze paresis may assist inreaching the correct diagnosis.

doi:10.1016/j.jocn.2010.07.023

1616 Abstracts / Journal of Clinical Neuroscience 17 (2010) 1610–1638