OBJECTIVE: The diagnosis of amyotrophic lateral sclerosis (ALS) relies on stringent clinical criteria, resulting in diagnostic delay and inevitably the institution of appropriate therapy. Cortical hyperexcitability, as assessed by the novel threshold tracking transcranial magnetic stimulation (TTTMS) technique, appears as an early feature of ALS. Consequently, the present study assessed the diagnostic utility of threshold tracking TMS and developed algorithms to aid the diagnosis of ALS. METHODS: Prospective studies were undertaken on a cohort of 156 consecutive patients with neuromuscular symptoms (104 ALS and 52 lower motor neuron syndrome, non-ALS syndrome, NALS) and 62 healthy controls. RESULTS: Short-interval intracortical inhibition (SICI) was significantly reduced in ALS patients (2.4 ± 0.9%) compared to NALS (8.7 ± 0.8%, P<0.0001) and controls (10.6 ± 0.8%, P < 0.0001). The MEP amplitude and intracortical facilitation were increased, while the cortical silent period duration was reduced in ALS, all indicative of cortical hyperexcitability. Analysis of receiver operating characteristic curves suggested that threshold tracking TMS distinguished ALS from NALS, with averaged (area under curve 0.76, P < 0.0001) and peak SICI 3 ms (area under curve 0.73, P<0.0001) being the most robust diagnostic markers. CONCLUSIONS: The presence of cortical hyperexcitability distinguishes ALS from mimic disorders. SIGNIFICANCE: The threshold tracking TMS techniques may prove useful as a diagnostic investigation for ALS.
OBJECTIVE: The diagnosis of amyotrophic lateral sclerosis (ALS) relies on stringent clinical criteria, resulting in diagnostic delay and inevitably the institution of appropriate therapy. Cortical hyperexcitability, as assessed by the novel threshold tracking transcranial magnetic stimulation (TTTMS) technique, appears as an early feature of ALS. Consequently, the present study assessed the diagnostic utility of threshold tracking TMS and developed algorithms to aid the diagnosis of ALS. METHODS: Prospective studies were undertaken on a cohort of 156 consecutive patients with neuromuscular symptoms (104 ALS and 52 lower motor neuron syndrome, non-ALS syndrome, NALS) and 62 healthy controls. RESULTS: Short-interval intracortical inhibition (SICI) was significantly reduced in ALS patients (2.4 ± 0.9%) compared to NALS (8.7 ± 0.8%, P<0.0001) and controls (10.6 ± 0.8%, P < 0.0001). The MEP amplitude and intracortical facilitation were increased, while the cortical silent period duration was reduced in ALS, all indicative of cortical hyperexcitability. Analysis of receiver operating characteristic curves suggested that threshold tracking TMS distinguished ALS from NALS, with averaged (area under curve 0.76, P < 0.0001) and peak SICI 3 ms (area under curve 0.73, P<0.0001) being the most robust diagnostic markers. CONCLUSIONS: The presence of cortical hyperexcitability distinguishes ALS from mimic disorders. SIGNIFICANCE: The threshold tracking TMS techniques may prove useful as a diagnostic investigation for ALS.
Authors: Gretchen M Thomsen; Genevieve Gowing; Jessica Latter; Maximus Chen; Jean-Philippe Vit; Kevin Staggenborg; Pablo Avalos; Mor Alkaslasi; Laura Ferraiuolo; Shibi Likhite; Brian K Kaspar; Clive N Svendsen Journal: J Neurosci Date: 2014-11-19 Impact factor: 6.167
Authors: Laura Ferraiuolo; Kathrin Meyer; Thomas W Sherwood; Jonathan Vick; Shibi Likhite; Ashley Frakes; Carlos J Miranda; Lyndsey Braun; Paul R Heath; Ricardo Pineda; Christine E Beattie; Pamela J Shaw; Candice C Askwith; Dana McTigue; Brian K Kaspar Journal: Proc Natl Acad Sci U S A Date: 2016-09-29 Impact factor: 11.205
Authors: Nimeshan Geevasinga; Parvathi Menon; Garth A Nicholson; Karl Ng; James Howells; Jillian J Kril; Con Yiannikas; Matthew C Kiernan; Steve Vucic Journal: JAMA Neurol Date: 2015-11 Impact factor: 18.302
Authors: Malcolm Proudfoot; Ricarda A L Menke; Rakesh Sharma; Claire M Berna; Stephen L Hicks; Christopher Kennard; Kevin Talbot; Martin R Turner Journal: Amyotroph Lateral Scler Frontotemporal Degener Date: 2015-08-27 Impact factor: 4.092