Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers.
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.


CONCLUSIONS
Additional factors other than simply SOD-1 mutation expression are required to trigger cortical hyperexcitability and neurodegeneration in FALS.
Vucic
Steve
S
Department of Neurology, Westmead Hospital, Western Clinical School, University of Sydney, Australia.
Winhammar
Jennica M C
JM
Rowe
Dominic B
DB
Kiernan
Matthew C
MC
D000200:Action Potentials / Q000235:genetics; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination / Q000379:methods; D010525:Peripheral Nerves / Q000503:physiopathology; D011712:Pyramidal Tracts / Q000473:pathology; D011930:Reaction Time / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1