Abstract

Background: While some regard the flail-arm syndrome as a variant of amyotrophic lateral sclerosis (ALS), others have argued that the flail-arm syndrome 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; 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.

Conclusion: The present 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 UMN dysfunction, the present study suggests that the flail-arm syndrome is an unusual variant of ALS.