Motor cortical function determines prognosis in sporadic ALS

Kazumoto Shibuya; Susanna B. Park; Nimeshan Geevasinga; Parvathi Menon; James Howells; Neil G. Simon; William Huynh; Yu Ichi Noto; Jürgen Götz; Jillian J. Kril; Lars M. Ittner; John Hodges; Glenda Halliday; Steve Vucic; Matthew C. Kiernan

doi:10.1212/WNL.0000000000002912

Motor cortical function determines prognosis in sporadic ALS

Kazumoto Shibuya, Susanna B. Park, Nimeshan Geevasinga, Parvathi Menon, James Howells, Neil G. Simon, William Huynh, Yu Ichi Noto, Jürgen Götz, Jillian J. Kril, Lars M. Ittner, John Hodges, Glenda Halliday, Steve Vucic, Matthew C. Kiernan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

77 Citations (Scopus)

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.

Original language	English
Pages (from-to)	513-520
Number of pages	8
Journal	Neurology
Volume	87
Issue number	5
DOIs	https://doi.org/10.1212/WNL.0000000000002912
Publication status	Published - 2 Aug 2016
Externally published	Yes

Access to Document

10.1212/WNL.0000000000002912

Cite this

@article{e83c67f425224ffab6c534924bbc4b63,

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.",

author = "Kazumoto Shibuya and Park, {Susanna B.} and Nimeshan Geevasinga and Parvathi Menon and James Howells and Simon, {Neil G.} and William Huynh and Noto, {Yu Ichi} and J{\"u}rgen G{\"o}tz and Kril, {Jillian J.} and Ittner, {Lars M.} and John Hodges and Glenda Halliday and Steve Vucic and Kiernan, {Matthew C.}",

year = "2016",

month = aug,

day = "2",

doi = "10.1212/WNL.0000000000002912",

language = "English",

volume = "87",

pages = "513--520",

journal = "Neurology",

issn = "0028-3878",

publisher = "AAN Enterprises",

number = "5",

}

TY - JOUR

T1 - Motor cortical function determines prognosis in sporadic ALS

AU - Shibuya, Kazumoto

AU - Park, Susanna B.

AU - Geevasinga, Nimeshan

AU - Menon, Parvathi

AU - Howells, James

AU - Simon, Neil G.

AU - Huynh, William

AU - Noto, Yu Ichi

AU - Götz, Jürgen

AU - Kril, Jillian J.

AU - Ittner, Lars M.

AU - Hodges, John

AU - Halliday, Glenda

AU - Vucic, Steve

AU - Kiernan, Matthew C.

PY - 2016/8/2

Y1 - 2016/8/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84982973161&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000002912

DO - 10.1212/WNL.0000000000002912

M3 - Article

C2 - 27402895

AN - SCOPUS:84982973161

SN - 0028-3878

VL - 87

SP - 513

EP - 520

JO - Neurology

JF - Neurology

IS - 5

ER -

Motor cortical function determines prognosis in sporadic ALS

Abstract

Access to Document

Other files and links

Fingerprint

Cite this