Hyperpolarisation of Motor Axons in Inclusion Body Myopathy, Paget’s Disease of the Bone and Frontotemporal Dementia (IBMPFD)

  • Dr Kishore Kumar, Royal North Shore Hospital, Australia
  • Dr Christina Liang, Royal North Shore Hospital, Australia
  • Dr Merrilee Needham, Royal North Shore Hospital, Australia
  • Prof David Burke, The University Of Sydney, Australia
  • Prof Carolyn Sue, Royal North Shore Hospital, Australia
  • Dr Karl Ng, Royal North Shore Hospital, Australia

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. In motor threshold eletrotonus, there was a greater threshold increase to hyperpolarising conditioning outside these limits in both members of Family A. All members of both families appeared to have increased superexcitability and reduced relative refractory period, but normal strength-duration time constants and subexcitable indices.
Conclusion: Motor axonal excitability studies demonstrated features consistent with hyperpolarisation in Family A. This may be specific for this genotype. Alternatively, it could be important in all patients with IBMPFD who have neuropathic features as part of their clinical phenotype.