Abnormalities in cortical and peripheral excitability in flail arm variant amyotrophic lateral sclerosis.
BACKGROUND
While some regard the flail arm syndrome as a variant of amyotrophic lateral sclerosis (ALS), others have argued that it is a distinct clinical entity. Consequently, the present study applied novel central and peripheral nerve excitability techniques to further explore disease pathophysiology in flail arm syndrome.


METHODS
Cortical and peripheral nerve excitability studies were undertaken in 11 flail arm patients, defined by muscle weakness limited to the proximal aspects of the upper limbs for at least 24 months.


RESULTS
Mean age at disease onset (60.3 years) was similar to other ALS phenotypes (58.3 years), with strong male predominance (male:female distribution: flail arm 10:1; ALS 1.5:1; p<0.05) and prolonged disease duration (flail arm 62.5 months; ALS 15.8 months; p<0.05). There was evidence of cortical hyperexcitability in flail arm patients, similar to findings in ALS, with reduction in short interval intracortical inhibition (flail arm 0.8 (0.6)%; ALS 4.1 (1.1)%; controls 8.5 (1.0)%; p<0.0001) and resting motor threshold (flail arm 53.4 (2.8)%; ALS 56.6 (1.8)%; controls 60.7 (1.5)%; p<0.05), along with an increase in motor evoked potential amplitude (flail arm 49.5 (9.0)%; ALS 44.4 (4.9)%; controls 25.8 (2.8)%; p<0.05). Peripheral nerve excitability studies demonstrated changes consistent with upregulation in persistent Na+ currents and reduction of slow K+ conductances, similar to findings in ALS.


CONCLUSIONS
This study has demonstrated the presence of cortical hyperexcitability in flail arm syndrome, along with abnormalities in peripheral nerve excitability, findings consistent with previous studies in other ALS phenotypes. By demonstrating the presence of upper motor neuron dysfunction, the present study suggests that the flail arm syndrome is an unusual variant of ALS.
Vucic
Steve
S
Prince of Wales Medical Research Institute and Prince of Wales Clinical School, University of New South Wales, Australia.
Kiernan
Matthew C
MC
D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D001132:Arm / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000503:physiopathology; D010641:Phenotype; D015221:Potassium Channels / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D013577:Syndrome
D015221:Potassium Channels; D015222:Sodium Channels