Axonal dysfunction,dysmyelination, and conduction failure in hereditary neuropathy with liability to pressure palsies

Introduction: Patients with hereditary neuropathy with liability to pressure palsies (HNPP) manifest with episodes of focal paresis when exposed to mechanical stress, although the basis for vulnerability to conduction block remains relatively unexplained. Methods: Axonal excitability techniques were utilized to provide insights into pathophysiological mechanisms in 13 HNPP patients, stimulating median motor and sensory axons at the wrist. Results: In HNPP, distal latencies were prolonged, and motor and sensory amplitudes were reduced. Threshold was increased. Depolarizing and hyperpolarizing electrotonus was greater, and resting current–threshold slope was reduced. There were greater threshold changes in superexcitability, and refractoriness was decreased. Conclusions: Taken together, excitability testing in patients with HNPP established axonal hyperpolarization in both motor and sensory axons that may be attributable to changes in nerve architecture. In turn, the hyperpolarized resting membrane potential in HNPP may be a major predisposing factor for development of conduction block with mechanical stresses. Muscle Nerve 49 : 858–865, 2014