Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers

Clin Neurophysiol. 2010 Oct;121(10):1781-5. doi: 10.1016/j.clinph.2010.02.164. Epub 2010 Apr 1.


Objective: Diffusion tensor imaging (DTI) recently identified structural abnormalities of corticomotoneurons in asymptomatic copper/zinc superoxide-dismutase-1 (SOD-1) gene mutation carriers. The potential existence of longstanding corticomotoneuronal dysfunction would clearly have consequences for the medical management of asymptomatic SOD-1 mutation carriers. To clarify this unexpected finding, DTI techniques were combined with threshold tracking transcranial magnetic stimulation (TMS) to assess the anatomical and functional integrity of corticomotoneurons in asymptomatic SOD-1 mutation carriers.

Methods: TMS studies were undertaken using a 90 mm circular coil on seven asymptomatic SOD-1 mutation carriers and results were compared to 62 healthy controls. DTI studies were carried out using a 3T magnetic resonance device in the same asymptomatic SOD-1 mutation carriers. Results were compared to age-matched healthy controls.

Results: In contrast to previous findings, there were no significant differences in fractional anisotropy (SOD-1 mutation carriers, 0.62+/-0.01; controls, 0.61+/-0.02, P=0.2) and trace apparent diffusion coefficient (SOD-1 mutation carriers, 0.003+/-0.0001; controls, 0.003+/-0.0001) in asymptomatic SOD-1 mutation carriers. Of further relevance, there were no significant differences in short-interval intracortical inhibition (SOD-1 mutation carriers, 7.9+/-3.4%; controls, 8.5+/-1.1%, P=0.26), intracortical facilitation (P=0.5), MEP amplitude (P=0.44), resting motor threshold (P=0.36) and cortical silent period duration (P=0.29).

Conclusions: Combined anatomical and functional modalities established normal integrity of corticomotoneurons in asymptomatic SOD-1 mutation carrier subjects.

Significance: Additional factors other than simply SOD-1 mutation expression are required to trigger cortical hyperexcitability and neurodegeneration in FALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics
  • Adult
  • Amyotrophic Lateral Sclerosis* / genetics
  • Amyotrophic Lateral Sclerosis* / pathology
  • Amyotrophic Lateral Sclerosis* / physiopathology
  • Brain Mapping
  • Cerebral Cortex / pathology*
  • Diffusion Tensor Imaging / methods
  • Electric Stimulation / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Motor Neurons / physiology*
  • Mutation / genetics*
  • Neurologic Examination / methods
  • Peripheral Nerves / physiopathology
  • Pyramidal Tracts / pathology
  • Reaction Time / genetics
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1


  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1