ArticleBrain pathology (Zurich, Switzerland)2020
Neuropathological profile of long-duration amyotrophic lateral sclerosis in military Veterans.
Article in Brain pathology (Zurich, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Stable speech BCI performance during slow progression of ALS: A longitudinal ECoG study.Research square · 2026Article
- Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies.Brain : a journal of neurology · 2023Article
- Dynamic effects of prognostic factors and individual survival prediction for amyotrophic lateral sclerosis disease.Annals of clinical and translational neurology · 2023Article
- Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies.medRxiv : the preprint server for health sciences · 2023Article
- Utility of the ALSFRS-R for predicting ALS and comorbid disease neuropathology: The Veterans Affairs Biorepository Brain Bank.Muscle & nerve · 2022Article
- MicroRNA Alterations in Chronic Traumatic Encephalopathy and Amyotrophic Lateral Sclerosis.Frontiers in neuroscience · 2022Article
- Histamine-4 Receptor: Emerging Target for the Treatment of Neurological Diseases.Current topics in behavioral neurosciences · 2022Review
- Fast Progression in Amyotrophic Lateral Sclerosis Is Associated With Greater TDP-43 Burden in Spinal Cord.Journal of neuropathology and experimental neurology · 2021Article
- Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants.Brain pathology (Zurich, Switzerland) · 2021Article
- Neuroimaging and advanced research techniques may lead to improved outcomes in military members suffering from traumatic brain injury.Trauma surgery & acute care open · 2021Review
- Characterizing tau deposition in chronic traumatic encephalopathy (CTE): utility of the McKee CTE staging scheme.Acta neuropathologica · 2020Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Although ALS typically leads to death within 3 to 5 years after initial symptom onset, approximately 10% of patients with ALS live more than 10 years after symptom onset. We set out to determine similarities and differences in clinical presentation and neuropathology in persons with ALS with long vs. those with standard duration. Participants were United States military Veterans with a pathologically confirmed diagnosis of ALS (n = 179), dichotomized into standard duration (<10 years) and long-duration (≥10 years). The ALS Functional Rating Scale-Revised (ALSFRS-R) was administered at study entry and semi-annually thereafter until death. Microglial density was determined in a subset of participants. long-duration ALS occurred in 76 participants (42%) with a mean disease duration of 16.3 years (min/max = 10.1/42.2). Participants with long-duration ALS were younger at disease onset (P = 0.002), had a slower initial ALS symptom progression on the ALSFRS-R (P < 0.001) and took longer to diagnose (P < 0.002) than standard duration ALS. Pathologically, long-duration ALS was associated with less frequent TDP-43 pathology (P < 0.001). Upper motor neuron degeneration was similar; however, long-duration ALS participants had less severe lower motor neuron degeneration at death (P < 0.001). In addition, the density of microglia was decreased in the corticospinal tract (P = 0.017) and spinal cord anterior horn (P = 0.009) in long-duration ALS. Notably, many neuropathological markers of ALS were similar between the standard and long-duration groups and there was no difference in the frequency of known ALS genetic mutations. These findings suggest that the lower motor neuron system is relatively spared in long-duration ALS and that pathological progression is likely slowed by as yet unknown genetic and environmental modifiers.
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