417: A consanguineous family with Frontotemporal Dementia/Motor Neuron Disease

Abstracts / Journal of Clinical Neuroscience 15 (2008) 337–369

416: Neuropathy is an integral component of the cerebellar ataxia with bilateral vestibulopathy syndrome David J. Szmulewicz, John A. Waterston, Catriona A. McLean, Elsdon Storey; Alfred Hospital, Victoria, Australia Purpose: To review patients with the syndrome of cerebellar ataxia with bilateral vestibulopathy (CABV), as described by Halmagyi et al. in Brain 2004, and to characterize the spectrum of the accompanying neuropathy, both clinically and electrophysiologically. Methods: A retrospective case review was performed of patients diagnosed with the syndrome of CABV to confirm that diagnostic criteria for this syndrome were met and to review the clinical and electrophysiological features of the accompanying neuropathy. Results: Six patients were identified in whom the diagnosis of CABV could be sustained. All had clinical evidence of vestibular failure, including abnormal dynamic visual acuity and/or impaired caloric and rotational chair results. All also showed broken-up (saccadic) smooth visual pursuit, with an abnormal visually-enhanced vestibulo-ocular reflex (VVOR) in the four in whom this was assessed. All demonstrated other evidence of cerebellar dysfunction, including impaired tandem gait, dysmetria or dysarthria. Nerve conduction studies demonstrated absent upper and lower limb sensory nerve action potentials (SNAPS) in four, with absent sural SNAPS and evidence of mild axonal motor neuropathy in the other two. Clinically, the neuropathy varied from small fibre predominance with almost complete loss of pin prick sensation accompanied by moderate distal reduction of vibration sense, to predominant large fibre length-dependent loss with complete preservation of pin prick perception. The subject with this latter clinical pattern underwent sural nerve biopsy, which revealed significant loss of both myelinated and non-myelinated fibres with 34% segmental remyelination. Conclusion: A sensory or sensory-motor neuropathy is an integral component of the CABV syndrome. Its anatomical extent and fibre distribution vary, but it may result in severe sensory loss, contributing significantly to the disability in this syndrome. doi:10.1016/j.jocn.2007.07.029

417: A consanguineous family with Frontotemporal Dementia/Motor Neuron Disease Clement T. Loy a, Bill S. Brooks a, Kevin Taddei b, A. Patton c, Catriona McLean d, Glenda M. Halliday a, Ralph Martins b, John B. Kwok a, Peter R. Schofield a; a Prince of Wales Medical Research Institute, Sydney, Australia; b McCusker Foundation for Alzheimer’s Disease Research & Edith Cowan University, Australia; c McCusker Foundation for Alzheimer’s Disease Research, Australia; d National Neural Tissue Resource Centre, Australia

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Aim: To describe the clinical, pathological and genetic features of a consanguineous family with Frontotemporal Dementia/Motor Neuron Disease (FTD-MND). Methods: Clinical assessment, immunohistochemistry and genetic sequencing. Results: We describe a consanguineous family with a sibship of eleven. The parents were first cousins who died at the age of 74 & 86 respectively with no neurologic, cognitive or behavioral symptoms. Six of the eleven siblings presented with a progressive behavioral syndrome consistent with frontal variant FTD (onset age 48–65), with extrapyramidal features and visual hallucinations in some. One other sibling presented with progressive bulbar palsy aged 49, while another presented with a progressive amnestic syndrome aged 49. The remaining three siblings (currently aged 68–81), and the 45 offspring of this sibship (currently aged 28–55) are all well. Neuropathological examination for two of the affected siblings found atrophy greatest in the frontal and temporal lobes, spongy changes in the cortex and tau-negative, ubiquitinpositive inclusion bodies. Sequencing of the Microtubule-Associated Protein Tau (MAPT) gene did not identify any mutations. Discussion: We have described a consanguineous FTDMND family with a history suggesting a recessive mode of inheritance. Mutation screening for other FTD genes and positional cloning using 10K Single Nucleotide Polymorphism mapping chips are in progress. There has only been one other recessive FTD family reported in the literature, found to have a homozygous deletion at codon 296 of the MAPT gene (not found in our family). Identification of a new recessive gene for FTD may have wider implications, particularly for patients with early onset FTD and no family history. doi:10.1016/j.jocn.2007.07.030

418: Tuberculous (TB) meningitis in Auckland Hospital 1965–2004: epidemiology, delays in treatment and complications Neil E. Anderson a, Jithendra Somaratne a, Deborah F. Mason b, David Holland c, Mark G. Thomas d; a Auckland City Hospital, New Zealand; b Christchurch Hospital, New Zealand; c Middlemore Hospital, New Zealand; d University of Auckland, New Zealand Purposes: To identify trends in the incidence and outcome of TB meningitis during the last 40 years; the frequency and reasons for delays in starting anti-TB treatment; and the frequency of complications. Methods: Retrospective review using multiple case finding methods. Definite TB meningitis was defined as (1) one or more of headache, neck stiffness, altered mental state and fever, (2) CSF pleocytosis and (3) culture of M.tuberculosis from the CSF or another site, or a positive PCR assay for M. tuberculosis. Probable TB meningitis was