Cortical contributions to the flail leg syndrome: Pathophysiological insights

Abstract

Cortical hyperexcitability has been identified as an intrinsic feature of amyotrophic lateral sclerosis (ALS). Consequently, the aim of the present study was to determine whether cortical hyperexcitability formed the pathophysiological basis for the flail leg syndrome (FL), an atypical ALS variant. Cortical excitability studies were undertaken on 18 FL patients, using the threshold tracking transcranial magnetic stimulation (TMS) technique, and results were compared to healthy controls, upper and lower limb-onset ALS as well as bulbar-onset and the flail arm variant ALS. Results showed that cortical hyperexcitability was a feature of FL and was heralded by a significant reduction of short-interval intracortical inhibition (FL 7.2 ± 1.8%; controls 13.2 ± 0.8%, p <0.01) and cortical silent period (CSP) duration (FL 181.7 ± 10.8ms; controls 209.8 ± 3.4ms; p <0.05) along with an increase in motor evoked potential amplitude (FL 29.2 ± 5.1%; controls 18.9 ± 1.2%, p <0.05). The degree of cortical hyperexcitability was comparable between FL and other ALS phenotypes, defined by site of disease onset. In addition, the CSP duration correlated with biomarkers of peripheral neurodegeneration in FL. In conclusion, cortical hyperexcitability is a feature of the flail leg syndrome, being comparable to other ALS phenotypes. Importantly, cortical hyperexcitability correlates with neurodegeneration, and as such may contribute to the underlying pathophysiology in FL.

Key words:

• Flail leg syndrome
• cortical hyperexcitability
• SICI

Acknowledgements

This study was supported by a research grant from the Motor Neuron Disease Research Institute of Australia, National Health and Medical Research Council of Australia and is gratefully acknowledged. This work was also supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neuron disease, from the National Health and Medical research Council of Australia Program Grant and the Pfizer Neuroscience Grant.

Declaration of interest

The authors declare no conflicts of interest.