Kazumoto Shibuya1, Susanna B Park1, Nimeshan Geevasinga1, Parvathi Menon1, James Howells1, Neil G Simon1, William Huynh1, Yu-Ichi Noto1, Jürgen Götz1, Jillian J Kril1, Lars M Ittner1, John Hodges1, Glenda Halliday1, Steve Vucic1, Matthew C Kiernan2. 1. From the Brain and Mind Centre (K.S., S.B.P., J.H., W.H., Y.-i.N., M.C.K.), Westmead Clinical School (N.G., P.M., S.V.), and Discipline of Pathology (J.J.K.), Sydney Medical School, University of Sydney; St. Vincent's Clinical School (N.G.S.), Prince of Wales Clinical School (W.H.), and Dementia Research Unit, School of Medical Sciences (L.M.I.), University of New South Wales (J.H., G.H.), Sydney; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute (J.G.), The University of Queensland; and Neuroscience Research Australia (L.M.I., J.H., G.H.), Sydney, Australia. 2. From the Brain and Mind Centre (K.S., S.B.P., J.H., W.H., Y.-i.N., M.C.K.), Westmead Clinical School (N.G., P.M., S.V.), and Discipline of Pathology (J.J.K.), Sydney Medical School, University of Sydney; St. Vincent's Clinical School (N.G.S.), Prince of Wales Clinical School (W.H.), and Dementia Research Unit, School of Medical Sciences (L.M.I.), University of New South Wales (J.H., G.H.), Sydney; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute (J.G.), The University of Queensland; and Neuroscience Research Australia (L.M.I., J.H., G.H.), Sydney, Australia. matthew.kiernan@sydney.edu.au.
Abstract
OBJECTIVE: To study the relationship between cortical function and survival in amyotrophic lateral sclerosis (ALS). METHODS: A total of 216 referrals were screened, and participants with familial ALS or an inexcitable cortex were excluded. Clinical measures and phenotyping from 169 patients with sporadic ALS were combined with an assessment of cortical function using threshold tracking transcranial magnetic stimulation with indices including short interval intracortical inhibition (SICI). Peripheral nerve studies were collected, incorporating compound muscle action potential amplitude. Clinical prognostic factors were recorded longitudinally, including ALS Functional Rating Scale-Revised (ALSFRS-R). RESULTS: Compared to 109 healthy controls, 169 patients had reduced SICI (p < 0.0001). In survival analysis, 105 patients progressed to death with an estimated median survival time of 37 months. In patients with less than 2 years disease duration (n = 140), those with bulbar onset (p = 0.017), rapid vital capacity (VC) decline (p < 0.0001), rapid ALSFRS-R decline (p < 0.0001), and reduced averaged SICI (p = 0.047) had a poorer prognosis. Multivariate analysis identified rapid VC decline (p < 0.0001), rapid ALSFRS-R decline (p = 0.0060), and reduced averaged SICI (p = 0.011) as factors independently associated with a shorter survival. CONCLUSIONS: Cortical dysfunction appears to be a prognostic marker in patients with ALS within 2 years of disease onset, such that patients with reduced averaged SICI, indicative of intracortical hyperexcitability, demonstrated a worse prognosis.
OBJECTIVE: To study the relationship between cortical function and survival in amyotrophic lateral sclerosis (ALS). METHODS: A total of 216 referrals were screened, and participants with familial ALS or an inexcitable cortex were excluded. Clinical measures and phenotyping from 169 patients with sporadic ALS were combined with an assessment of cortical function using threshold tracking transcranial magnetic stimulation with indices including short interval intracortical inhibition (SICI). Peripheral nerve studies were collected, incorporating compound muscle action potential amplitude. Clinical prognostic factors were recorded longitudinally, including ALS Functional Rating Scale-Revised (ALSFRS-R). RESULTS: Compared to 109 healthy controls, 169 patients had reduced SICI (p < 0.0001). In survival analysis, 105 patients progressed to death with an estimated median survival time of 37 months. In patients with less than 2 years disease duration (n = 140), those with bulbar onset (p = 0.017), rapid vital capacity (VC) decline (p < 0.0001), rapid ALSFRS-R decline (p < 0.0001), and reduced averaged SICI (p = 0.047) had a poorer prognosis. Multivariate analysis identified rapid VC decline (p < 0.0001), rapid ALSFRS-R decline (p = 0.0060), and reduced averaged SICI (p = 0.011) as factors independently associated with a shorter survival. CONCLUSIONS:Cortical dysfunction appears to be a prognostic marker in patients with ALS within 2 years of disease onset, such that patients with reduced averaged SICI, indicative of intracortical hyperexcitability, demonstrated a worse prognosis.
Authors: Juhyun Kim; Ethan G Hughes; Ashwin S Shetty; Paola Arlotta; Loyal A Goff; Dwight E Bergles; Solange P Brown Journal: J Neurosci Date: 2017-08-17 Impact factor: 6.167
Authors: Smriti Agarwal; Elizabeth Highton-Williamson; Jashelle Caga; José M Matamala; Thanuja Dharmadasa; James Howells; Margaret C Zoing; Kazumoto Shibuya; Nimeshan Geevasinga; Steve Vucic; John R Hodges; Rebekah M Ahmed; Matthew C Kiernan Journal: J Neurol Date: 2018-06-04 Impact factor: 4.849
Authors: Michael D Weiss; Eric A Macklin; Courtney E McIlduff; Steve Vucic; Brian J Wainger; Matthew C Kiernan; Stephen A Goutman; Namita A Goyal; Seward B Rutkove; Shafeeq S Ladha; I-Hweii Amy Chen; Matthew B Harms; Thomas H Brannagan; David Lacomis; Sasha Zivkovic; Maxwell Ma; Leo H Wang; Zachary Simmons; Michael H Rivner; Jeremy M Shefner; Merit E Cudkowicz; Nazem Atassi Journal: Muscle Nerve Date: 2020-12-31 Impact factor: 3.217
Authors: Xuan Huang; Kasper C D Roet; Liying Zhang; Amy Brault; Allison P Berg; Anne B Jefferson; Jackie Klug-McLeod; Karen L Leach; Fabien Vincent; Hongying Yang; Anthony J Coyle; Lyn H Jones; Devlin Frost; Ole Wiskow; Kuchuan Chen; Rie Maeda; Alyssa Grantham; Mary K Dornon; Joseph R Klim; Marco T Siekmann; Dongyi Zhao; Seungkyu Lee; Kevin Eggan; Clifford J Woolf Journal: Cell Rep Date: 2021-06-08 Impact factor: 9.423