Axonal excitability in viral polyneuropathy and nucleoside neuropathy in HIV patients

J Neurol Neurosurg Psychiatry. 2011 Sep;82(9):978-80. doi: 10.1136/jnnp.2009.203091. Epub 2010 Jul 16.

Abstract

HIV infection is associated with several forms of peripheral neuropathy, the most common being a distal symmetrical polyneuropathy due to HIV infection ('DSP'). Direct viral effects are an important cause (hereafter termed viral neuropathy (VN)), but sometimes, it is due to nucleoside antiretroviral drug therapy (nucleoside neuropathy (NN)). Mechanisms of disease are incompletely understood, with some evidence implicating HIV envelope glycoprotein gp120 mediated neuronal apoptosis for the former and mitochondrial toxicity ± DNA polymerase γ involvement in the latter. The authors studied 16 HIV positive patients, 14 of whom had neuropathy (10 VN; 4 NN), clinically, with conventional nerve-conduction studies (NCS), and with measurements of the excitability of motor and sensory axons in the median nerve. Clinically neuropathic patients were all symptomatic, and 12 had abnormalities in NCS. There were no changes in the excitability of sensory or motor axons in VN, but there were in the NN group. These were consistent with depolarisation of the internodal membrane ('fanned in' threshold electrotonus, increased resting current--voltage slope, reduced superexcitability) but with sparing of nodal properties (absolute threshold, strength--duration properties, refractoriness). Membrane abnormalities in VN are not diffuse and are likely to result from a more focal process, presumably proximal, while those in NN most likely relate to mitochondrial dysfunction. Confirmation of these findings may allow neurophysiological distinction between these entities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / physiopathology
  • Action Potentials / drug effects
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Axons / drug effects
  • Axons / physiology*
  • Electrophysiological Phenomena
  • Energy Metabolism / drug effects
  • Female
  • HIV Infections / complications
  • HIV Infections / physiopathology*
  • Humans
  • Ischemia / pathology
  • Male
  • Middle Aged
  • Models, Neurological
  • Neural Conduction / drug effects
  • Neurologic Examination
  • Nucleosides / physiology*
  • Polyneuropathies / chemically induced
  • Polyneuropathies / etiology
  • Polyneuropathies / physiopathology*

Substances

  • Nucleosides