Science News: MRI Clustering Reveals Three ALS Subtypes With Unique Neurodegeneration Patterns

Submitted by: Raymond Rosales, MD, PhD
Edited by: Eman Tawfik, MD
 
Tan HHG, Westeneng HJ, Nitert AD, et al. MRI clustering reveals three ALS subtypes with unique neurodegeneration patterns. Ann Neurol. 2022;92(6):1030-1045. doi:10.1002/ana.26488
 
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which patients are confronted with speech impairment, muscle wasting and weakness, and eventually respiratory insufficiency and death. The purpose of this study was to identify subtypes of ALS by comparing patterns of neurodegeneration using brain magnetic resonance imaging (MRI) and explore their phenotypes. The study included 488 ALS patients and 338 control subjects.

MRI clustering algorithm divided patients with ALS into three subgroups. All subgroups displayed involvement of the precentral gyrus, and each has a unique neurodegeneration pattern, and is associated with distinct clinical characteristics and cognitive profiles. The three subgroups are: (1) pure motor involvement (pure motor cluster [PM]), (2) orbitofrontal and temporal involvement (frontotemporal cluster [FT]), and (3) involvement of the posterior cingulate cortex, parietal white matter, temporal operculum, and cerebellum (cingulate-parietal–temporal cluster [CPT]).
 
Comments: With the increase in knowledge over the years, the remarkable heterogeneity of ALS is becoming more apparent in many aspects of the disease, such as the primary disease site, progression rate, the presence of cognitive and behavioral impairment, genetic predisposition, and pathophysiological processes. Life expectancy is also highly variable, ranging from a few months to more than 10 years. This heterogeneity means that providing an accurate prognosis is complicated for clinicians and, as a result, leaves patients with uncertainty about their future. To advance our understanding of ALS, it is crucial to get to the core of this heterogeneity, in particular, because it seems highly likely that treatments will need to be tailored to individual patient characteristics. Neuroimaging may help shed the light on ALS heterogenicity as demonstrated in this study.