Introduction: Inclusion-body myopathy, Paget disease of the bone, and fronto temporal dementia (IBMPFD) is an autosomal dominant disorder due to mutations in the valosin-containing protein (VCP) gene. Patients with this disorder may have neuropathic or myopathic features.
Methods: Peripheral nerve function and axonal excitability were studied in three members from two families with VCP mutations (p.Arg155Leuand p.Leu198Trp).
Results: Patients from the first family had neurogenic patterns on needle electromyography (EMG), where as those in the second family had myopathic EMG changes. In threshold electrotonus for motor axons, the changes to depolarizing and hyperpolarizing conditioning currents were at or outside control limits in all three patients. Super excitability was increased, and the relative refractory period was reduced. The strength-duration time constant was normal. In sensory axons of all three patients, there were similar changes in threshold electrotonus, but not in super excitability.
Discussion: These features are best explained by axonalhyper polarization. The findings provide insight into the patho physiological mechanisms in these genotypes and, possibly, into all patients with IBMPFD.