title: Regionality of disease progression predicts prognosis in amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating neurological syndrome in which motor neurons degenerate relentlessly. Although the site of onset and the rate of spread have been studied extensively, little is known about whether focal as opposed to diffuse disease affects prognosis. We therefore tested the hypothesis that regionality of disease burden is a prognostic factor in ALS. We analysed clinical data from two large multicentre, longitudinal trials. Regionality was defined as the difference in progression rates in three domains as measured by the revised ALS Functional Rating Scale, omitting the respiratory domain from analysis. We used death by trial end as the outcome variable and tested this by logistic regression against predictor variables including regionality and overall rate of disease progression. There were 561 patients. Regionality of disease was independently associated with significantly higher chance of death by study end (odds ratio most diffuse against most focal category 0.354 (0.191, 0.657), p = 0.001), with a direct relationship between degree of regionality and odds of death. We have shown using clinical trial data that focal disease is associated with a worse prognosis in ALS. Measures of regionality warrant further independent consideration in the development of future prognostic models.
authors.affiliation: a Department of Basic and Clinical Neuroscience , Institute of Psychiatry, Psychology & Neuroscience, King's College London , UK.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: van der Kleij
authors.affiliation: a Department of Basic and Clinical Neuroscience , Institute of Psychiatry, Psychology & Neuroscience, King's College London , UK.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Jones
authors.affiliation: b Institute of Health and Society, University of Newcastle , UK.
authors.forename: I Nick
authors.initials: IN
authors.lastname: Steen
authors.affiliation: c Walton Centre NHS Trust , Liverpool , UK.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Young
authors.affiliation: d Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield , Sheffield , UK.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
authors.affiliation: a Department of Basic and Clinical Neuroscience , Institute of Psychiatry, Psychology & Neuroscience, King's College London , UK.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Shaw
authors.affiliation: e Brighton and Sussex Medical School, Trafford Centre for Biomedical Research , Falmer, Brighton, UK.
authors.forename: P Nigel
authors.initials: PN
authors.lastname: Leigh
authors.affiliation: f Nuffield Department of Clinical Neurosciences , Oxford University , Oxford , UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Turner
authors.affiliation: a Department of Basic and Clinical Neuroscience , Institute of Psychiatry, Psychology & Neuroscience, King's College London , UK.
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D010244:Bulbar Palsy, Progressive / Q000209:etiology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016015:Logistic Models; D035002:Lower Extremity / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology*; D016017:Odds Ratio; D011379:Prognosis; D012132:Respiratory Muscles / Q000503:physiopathology*; D015996:Survival Rate; D034941:Upper Extremity / Q000503:physiopathology*
keywords: ALSFRS-R; Amyotrophic lateral sclerosis; phenotype; prognosis; spread