title: Motor cortical function determines prognosis in sporadic ALS.
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.
authors.affiliation: 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.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: 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.
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Nimeshan
authors.initials: N
authors.lastname: Geevasinga
authors.affiliation: 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.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Menon
authors.affiliation: 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.
authors.forename: James
authors.initials: J
authors.lastname: Howells
authors.affiliation: 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.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Simon
authors.affiliation: 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.
authors.forename: William
authors.initials: W
authors.lastname: Huynh
authors.affiliation: 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.
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Noto
authors.affiliation: 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.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
authors.affiliation: 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.
authors.forename: Jillian J
authors.initials: JJ
authors.lastname: Kril
authors.affiliation: 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.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Ittner
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Hodges
authors.affiliation: 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.
authors.forename: Glenda
authors.initials: G
authors.lastname: Halliday
authors.affiliation: 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.
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.affiliation: 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.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000502:physiology; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D011379:Prognosis; D016019:Survival Analysis; D050781:Transcranial Magnetic Stimulation