Pathophysiology of HNPP explored using axonal excitability

J Neurol Neurosurg Psychiatry. 2013 Jul;84(7):806-12. doi: 10.1136/jnnp-2012-304576. Epub 2013 Feb 16.


Objective: Hereditary liability to pressure palsies (HNPP) is an autosomal dominant disorder of myelination resulting in susceptibility to pressure palsies from compression or stretching of peripheral nerves.

Patients and methods: This study examined axonal excitability at two sites (one distal and one proximal) in five patients with biopsy and genetically proven HNPP to understand the pathophysiology of the disease. Comparisons were made with age-matched control subjects as well as five Charcot-Marie-Tooth type 1A patients to contrast the findings and explain the different phenotypes of diseases affecting the same gene.

Results: Changes in axonal excitability were found in HNPP subjects, but these were not uniform along the nerve: at the wrist there were prominent alterations in threshold electrotonus, whereas at the elbow there were only subtle alterations in the recovery cycle and the response to strong long-lasting hyperpolarisation. Threshold was raised at both sites, but the nerves were probably not hyperpolarised. Not unexpectedly, changes in CMT1A subjects were more marked than those in HNPP subjects and were uniform along the nerve.

Conclusions: Structural abnormalities at the node of Ranvier are sufficient to explain the changes in axonal excitability in HNPP, and these abnormalities would predispose the nerves to conduction block when subjected to pressure or stretch.

Keywords: Hmsn (Charcot-Marie-Tooth); Neuropathy; Neurophysiol, Clinical.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthrogryposis / genetics*
  • Arthrogryposis / physiopathology*
  • Axons*
  • Biopsy
  • Brachial Plexus / injuries
  • Charcot-Marie-Tooth Disease / genetics
  • Charcot-Marie-Tooth Disease / physiopathology
  • Data Interpretation, Statistical
  • Demyelinating Diseases / pathology
  • Elbow / innervation
  • Electric Stimulation
  • Female
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Hereditary Sensory and Motor Neuropathy / physiopathology*
  • Humans
  • Longitudinal Studies
  • Male
  • Median Nerve / physiopathology
  • Middle Aged
  • Models, Statistical
  • Motor Neurons
  • Muscle Tonus
  • Myelin Sheath / pathology
  • Potassium Channels / metabolism
  • Pressure
  • Reproducibility of Results
  • Sural Nerve / pathology
  • Wrist / innervation


  • Potassium Channels

Supplementary concepts

  • Tomaculous neuropathy