title: 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.
authors.affiliation: a Sydney Medical School, University of Sydney , Sydney , Australia .|b Westmead Hospital , Sydney , Australia .
authors.forename: Parvathi
authors.initials: P
authors.lastname: Menon
authors.affiliation: a Sydney Medical School, University of Sydney , Sydney , Australia .|b Westmead Hospital , Sydney , Australia .
authors.forename: Nimeshan
authors.initials: N
authors.lastname: Geevasinga
authors.affiliation: a Sydney Medical School, University of Sydney , Sydney , Australia .|c Royal North Shore Hospital , Sydney , Australia , and.
authors.forename: Con
authors.initials: C
authors.lastname: Yiannikas
authors.affiliation: a Sydney Medical School, University of Sydney , Sydney , Australia .|d Brain and Mind Centre , Royal Prince Alfred Hospital , Sydney ,   Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.affiliation: a Sydney Medical School, University of Sydney , Sydney , Australia .|b Westmead Hospital , Sydney , Australia .
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D007866:Leg / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000502:physiology; D011446:Prospective Studies; D050781:Transcranial Magnetic Stimulation
keywords: Flail leg syndrome; SICI; cortical hyperexcitability