Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis

Familial amyotrophic lateral sclerosis (FALS) is an inherited neurodegenerative disorder of the motor neurons. While 10–15% of cases are caused by mutations in the copper/zinc superoxide-dismutase-1 (SOD-1) gene, the dying-forward hypothesis, in which corticomotoneurons induce anterograde excitotoxi...

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Bibliographic Details
Published in:Brain (London, England : 1878) England : 1878), 2008-06, Vol.131 (6), p.1540-1550
Main Authors: Vucic, Steve, Nicholson, Garth A., Kiernan, Matthew C.
Format: Article
Language:English
Subjects:
Adult
Aged
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - physiopathology
Biological and medical sciences
Case-Control Studies
cortical hyperexcitability
Evoked Potentials, Motor
familial ALS
Follow-Up Studies
Humans
Median Nerve - physiology
Medical sciences
Middle Aged
Motor Cortex - physiology
Motor Neurons - physiology
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Mutation
Neurology
Sensory Thresholds
SOD-1
Superoxide Dismutase - genetics
Superoxide Dismutase-1
Transcranial Magnetic Stimulation
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Summary:Familial amyotrophic lateral sclerosis (FALS) is an inherited neurodegenerative disorder of the motor neurons. While 10–15% of cases are caused by mutations in the copper/zinc superoxide-dismutase-1 (SOD-1) gene, the dying-forward hypothesis, in which corticomotoneurons induce anterograde excitotoxic motoneuron degeneration, has been proposed as a potential mechanism. The present study applied novel threshold tracking transcranial magnetic stimulation techniques to investigate the mechanisms underlying neurodegeneration in FALS. Studies were undertaken in 14 asymptomatic and 3 pre-symptomatic SOD-1 mutation carriers, followed longitudinally for up to 3-years. The pre-symptomatic subjects were asymptomatic at the time of their initial study but developed symptoms during the follow-up period. Results were compared to 7 SOD-1 FALS patients, 50 sporadic ALS patients and 55 normal controls. Short-interval intracortical inhibition (SICI) was significantly reduced in SOD-1 FALS (−1.2 ± 0.6%) and sporadic ALS patients (−0.7 ± 0.3%) compared to asymptomatic SOD-1 mutation carriers (9.8 ± 1.5%, P
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awn071