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ALS Symptoms Linked to Changes in Spinal Cord

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disease that affects cells in the brain and/or spinal cord that control muscles. Individuals with ALS may experience muscle weakness or stiffness, and over time lose their ability to move, speak, eat, or breathe. There is no cure for this fatal motor neuron disease.

For the first time researchers have identified a relationship between the distinct patterns of ALS symptoms and microscopic changes in the brain and spinal cord.  VA Boston Healthcare and Boston University School of Medicine (BUSM) researchers at the VA Biorepository Brain Bank (VABBB) studied whether a commonly used ALS rating system to track disease progression, the ALS functional rating scale-revised (ALSFRS-R), was related to microscopic changes in the brain and spinal cord in 93 Veterans who donated their brain and spinal cord to the VABBB upon death.

Veterans or their caregivers completed the ALS rating system and other measures while living. The rating system measures muscle weakness in the arms/legs, swallowing/speech, and breathing resulting from ALS. The researchers, led by Leigh Colvin, PhD, found that Veterans could be grouped into different patterns, or clusters, of muscle weakness symptoms, e.g.one cluster reported weakness in all muscle groups, while another maintained their ability to speak and swallow until death. ALS clusters showing more severe symptoms also had more severe microscopic changes in the brain and spinal cord related to ALS.

The relationship between the cluster groups and microscopic ALS-specific changes had not been shown previously and suggests that using the functional rating system to identify different patterns of ALS disease progression may lead to better assessment of current and future ALS treatments. BUSM assistant professor of neurology Christopher Brady, PhD, the study’s senior author and scientific director of the VABBB noted  “there was previous evidence suggesting that the ALSFRS-R was related to more global brain changes seen on neuroimaging, but this is the first study to show that different patterns of ALS symptoms seen on the ALSFRS-R are related to microscopic changes specific to ALS at the level of the neuron. We hope these findings promote the examination of ALS symptom subgroups to better tailor future treatments for ALS.”

These findings, which appear online in Muscle & Nerve, support the growing consensus that more detailed examination of the scores on the ALS rating system may improve the tracking of different patterns of disease progression in ALS and assist researchers in identifying subgroups for more specific treatments in clinical trials.

Reference: Colvin LE, Foster ZW, Stein TD, et al. Utility of the ALSFRS-R for predicting ALS and comorbid disease neuropathology: The veterans affairs biorepository brain bank. Muscle Nerve. 2022. doi: 10.1002/mus.27635


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