title: Head injury does not alter disease progression or neuropathologic outcomes in ALS.
abstract: OBJECTIVE
  To study the effects of head injury on disease progression and on neuropathologic outcomes in amyotrophic lateral sclerosis (ALS).
  
  
  METHODS
  Patients with ALS were surveyed to obtain head injury history, and medical records were reviewed. Linear regression was performed to determine if head injury was a predictor for mean monthly decline of Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R), while controlling for confounders. Head injury history was obtained from family members of ALS autopsy cases. The frequency of tau proteinopathy, brain TDP-43 inclusions, and pathologic findings of Alzheimer disease (AD) were examined in ALS cases with head injury compared to cases without. Logistic regression was performed with each neuropathologic diagnosis as an outcome measure and head injury as a predictor variable.
  
  
  RESULTS
  No difference was seen in rate of decline of the ALSFRS-R between patients with head injury (n = 24) and without (n = 76), with mean monthly decline of -0.9 for both groups (p = 0.18). Of 47 ALS autopsy cases (n = 9 with head injury, n = 38 without), no significant differences were seen in the frequency of tau proteinopathy (11% with head injury; 24% without), TDP-43 in the brain (44% with head injury; 45% without), or AD pathology (33% with head injury; 26% without). Independent logistic regression models showed head injury was not a predictor of tau pathology (p = 0.42) or TDP-43 in the brain (p = 0.99).
  
  
  CONCLUSIONS
  Head injury was not associated with faster disease progression in ALS and did not result in a specific neuropathologic phenotype. The tau pathology described with chronic traumatic encephalopathy was found in ALS autopsy cases both with and without head injury.
authors.affiliation: From the Departments of Neurology (C.N.F., M.G., S.R.U., J.D.G.), Pathology (M.G., J.D.G.), and Environmental Health (M.K.), Emory University School of Medicine, Atlanta, GA. christina.nicole.fournier@emory.edu.
authors.forename: Christina N
authors.initials: CN
authors.lastname: Fournier
authors.affiliation: From the Departments of Neurology (C.N.F., M.G., S.R.U., J.D.G.), Pathology (M.G., J.D.G.), and Environmental Health (M.K.), Emory University School of Medicine, Atlanta, GA.
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.affiliation: From the Departments of Neurology (C.N.F., M.G., S.R.U., J.D.G.), Pathology (M.G., J.D.G.), and Environmental Health (M.K.), Emory University School of Medicine, Atlanta, GA.
authors.forename: Saila R
authors.initials: SR
authors.lastname: Upadhyayula
authors.affiliation: From the Departments of Neurology (C.N.F., M.G., S.R.U., J.D.G.), Pathology (M.G., J.D.G.), and Environmental Health (M.K.), Emory University School of Medicine, Atlanta, GA.
authors.forename: Mitch
authors.initials: M
authors.lastname: Klein
authors.affiliation: From the Departments of Neurology (C.N.F., M.G., S.R.U., J.D.G.), Pathology (M.G., J.D.G.), and Environmental Health (M.K.), Emory University School of Medicine, Atlanta, GA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Glass
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006259:Craniocerebral Trauma / Q000150:complications*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
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