Major advances in amyotrophic lateral sclerosis in 2020

Amyotrophic lateral sclerosis (ALS), a heterogeneous syndrome recognised clinically as a progressive degeneration of the upper and lower motor neurons, is traditionally classed as a neuromuscular disorder. However, major advances in cell and molecular biology, neuroimaging, neuroelectric signal analyses, and neuropathology have categorically shown that ALS should be considered to be a neurodegenerative disorder, albeit with a substantial neuromuscular component. 1 van Es MA Goedee HS Westeneng HJ Nijboer TCW van den Berg LH Is it accurate to classify ALS as a neuromuscular disorder?. Expert Rev Neurother. 2020; 20: 895-906 Crossref PubMed Scopus (5) Google Scholar Although the biological processes underlying the pathogenesis and progression of the disease are multifactorial, there is increasing evidence that ALS is characterised by early cortical hyperexcitability with altered synaptic integrity, possibly mediated by the deposition of TAR DNA-binding protein 43 (TDP-43), 2 Dyer MS Reale LA Lewis KE et al. Mislocalisation of TDP-43 to the cytoplasm causes cortical hyperexcitability and reduced excitatory neurotransmission in the motor cortex. J Neurochem. 2020; (published online Oct 16.)https://doi.org/10.1111/jnc.15214 Crossref PubMed Scopus (5) Google Scholar followed by more widespread disruption of neuronal networks. 3 Menon P Higashihara M van den Bos M Geevasinga N Kiernan MC Vucic S Cortical hyperexcitability evolves with disease progression in ALS. Ann Clin Transl Neurol. 2020; 7: 733-741 Crossref PubMed Scopus (14) Google Scholar