Abstract
Motor neuron diseases are a spectrum of diseases characterized by degeneration of the upper motor neuron (UMN) and/or lower motor neuron (LMN). The motor neuron diseases include amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, bulbar atrophy, progressive muscular atrophy, progressive bulbar palsy, and familial myotrophic lateral sclerosis.
Clinical variability is high including muscle cramps, spasticity, muscle weakness, muscle atrophy, dysarthria, dysphagia, dyspnea, respiratory insufficiency, and cognitive impairment.
On MR imaging, bilateral hyperintensities along corticospinal tract as well as hypointensity in the precentral gyrus due to iron deposition are seen.
Muscle tissue shows fascicular atrophy and fiber type grouping. The spinal cord displays loss of upper and lower motor neurons, central chromatolysis, astrogliosis, and microgliosis. Inclusions in neurons are manifold and include skein-like inclusions (positive for ubiquitin, p62, TDP-43, and FUS/TLS), round inclusions (positive for ubiquitin and phosphorylated neurofilament), Bunina bodies (specific hallmark of ALS; positive for cystatin C and transferrin), Lewy body-like hyaline inclusions, and basophilic inclusions.
Possible pathogenic mechanisms and mutations in many genes have been identified which play a role in excitotoxicity, oxidative stress, reactive oxygenating species toxicity, mitochondrial dysfunction, impairment of axonal transport, cytoskeletal derangement, protein aggregation, endoplasmic reticulum stress, abnormal RNA processing, and neuroinflammation.
Treatment relies on drugs (e.g., riluzole (2-amino-6-[trifluoromethoxy]benzothiazole)), nutritional support, respiratory support, and symptomatic management. Motor neuron disorders are progressive disorders with a median life expectancy of 2.5–3.5 years. Favorable prognostic factors include early age of onset, progressive muscular atrophy, and primary lateral sclerosis while poor prognostic factors include bulbar onset, older age, and female sex.
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Weis, S. et al. (2019). Neurodegenerative Diseases: Motor Neuron Diseases. In: Imaging Brain Diseases. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1544-2_39
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DOI: https://doi.org/10.1007/978-3-7091-1544-2_39
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