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53. Peripheral axonal hyperpolarisation in Inclusion Body Myopathy, Paget’s disease of the bone and Frontotemporal Dementia (IBMPFD)

Kumar, K., Liang, C., Needham, M., Burke, D., Sue, C. and Ng, K. (2010) 53. Peripheral axonal hyperpolarisation in Inclusion Body Myopathy, Paget’s disease of the bone and Frontotemporal Dementia (IBMPFD). Journal of Clinical Neuroscience, 17 (12). p. 1626.

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Objective: IBMPFD is an autosomal dominant disorder due to mutations in the valosin-containing protein (VCP) gene. We aimed to study the nerve axonal excitability properties in this disorder.

Methods: We studied 2 members from Family A with a novel VCP mutation (p.Arg155Leu) and 1 member from Family B with a known VCP mutation (p.Leu198Trp). The patients from Family A had a neurogenic pattern on needle electromyography (EMG) with no abnormality on nerve conduction studies, in contrast to the patient from Family B who had myopathic EMG changes. We performed motor and sensory nerve excitability studies and compared the results to controls.

Results: Comparisons were made to 95% confidence intervals in 50 normal subjects for motor and 27 normal subjects for sensory data. In motor threshold eletrotonus, there was a greater threshold increase to hyperpolarising conditioning current outside these limits in both members of Family A. All members of both families appeared to have increased superexcitability and reduced relative refractory period. Strength-duration time constant was increased in one (Family A), but subexcitability was normal in all. In sensory studies, similar changes in threshold electrotonus were seen in some but not in superexcitability, even though strength-duration was increased in all three.

Conclusion: Motor and sensory axonal excitability studies demonstrated features most consistent with hyperpolarisation. As this appeared most prominent in the motor studies of Family A, we conclude that this may be more pronounced for this genotype. Alternatively, it could be important in all patients with IBMPFD who have neuropathic features as part of their clinical phenotype. A possible mechanism is dysfunction of the ubiquitin-proteasomal system resulting in relative hyperactivity of the Na+/K+ pump.

Item Type: Journal Article
Publisher: Churchill Livingstone
Copyright: © 2010 Published by Elsevier Ltd.
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