Head Injury Does Not Alter Disease Progression or Neuropathologic Outcomes in Amyotrophic Lateral Sclerosis (ALS) 公开

Fournier, Christina Nicole (2014)

Permanent URL: https://etd.library.emory.edu/concern/etds/x920fx580?locale=zh
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Abstract

Background:Head injury has been examined as a risk factor for ALS that potentially accelerates neurodegeneration. A causal relationship between head injury and ALS has been proposed after observing pathologic findings of tau proteinopathy (the pathologic finding described with chronic traumatic encephalopathy (CTE)) and TDP-43 accumulation in the brains of professional athletes with ALS. Methods:ALS patients were surveyed to obtain head injury history, and clinical information was obtained from medical records. Head injury was defined as an event associated with loss of consciousness or requiring hospitalization, occurring greater than 1 year prior to ALS diagnosis. Demographic and clinical information from ALS patients with head injury was compared to ALS patients without. Linear regression was performed to determine if head injury is a predictor for rate of disease progression, as measured by the revised ALS functional rating scale (ALSFRS-R), while controlling for confounders. Additionally, head injury history was obtained from family members of ALS autopsy cases. The frequency of tau proteinopathy, TDP-43 proteinopathy in the brain, and pathologic findings of Alzheimer dementia (AD) were examined in ALS cases with head injury compared to ALS 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 ALSFRS-R between ALS patients with head injury (n=24) and without (n=76), with mean monthly ALSFRS-R 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 proteinopathy 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 significant predictor of tau pathology (OR=0.4, p=0.42) or TDP-43 brain pathology (OR=0.99, p=0.99). Conclusion: Head injury was not associated with faster disease progression in ALS. Additionally, head injury did not result in a specific neuropathologic phenotype in ALS. The tau pathology described with CTE occurred in ALS autopsy cases both with and without head injury.

Table of Contents

1. Introduction...........................1

2. Background............................3

3. Methods................................5

4. Results..................................9

5. Discussion and Conclusion.........11

6. References.............................13

7. Tables...................................17

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