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TBK1 mutation spectrum in an extended European patient cohort with frontotemporal dementia and amyotrophic lateral sclerosis human mutation. 20 Geronimo AM, Martin A, Simmons Z. Inertial sensing of step kinematics in ambulatory patients with ALS and related motor neuron diseases. Arterial blood gas analysis: base excess and carbonate are predictive of noninvasive ventilation adaptation and survival in amyotrophic lateral sclerosis. [Extracted from the article]

Background and Objectives: Pathogenic variations in fused in sarcoma (FUS) are among the most common genetic causes of amyotrophic lateral sclerosis (ALS) worldwide. They are supposedly characterized by a homogeneous pure motor phenotype with early-onset and short disease duration. However, a few FUS- mutated cases with a very late disease onset and slow progression have been reported. To analyze genotype-phenotype correlations and identify the prognostic factors in FUS -ALS cases., Methods: We identified and cross-sectionally analyzed 22 FUS -ALS patient histories from a single-center cohort of 2,615 genetically tested patients and reviewed 289 previously published FUS -ALS cases. Survival analysis was performed by Kaplan-Meier survival curves, followed by the log-rank test and multivariate Cox analysis., Results: Survival of FUS -ALS is age-dependent: In our cohort, early-onset cases had a rapid disease progression and short survival ( p = 0.000003) while the outcome of FUS -mutated patients with mid-to-late onset did not differ from non- FUS -ALS patients ( p = 0.437). Meta-analysis of literature data confirmed this trend ( p = 0.00003). This survival pattern is not observed in other ALS-related genes in our series. We clustered FUS -ALS patients in 3 phenotypes: (1) axial ALS, with upper cervical and dropped-head onset in mid-to-late adulthood; (2) benign ALS, usually with a late-onset and slow disease progression; and (3) juvenile ALS, often with bulbar onset and preceded by learning disability or mild mental retardation. Those phenotypes arise from different mutations., Discussion: We observed specific genotype-phenotype correlations of FUS -ALS and identified age at onset as the most critical prognostic factor. Our results demonstrated that FUS mutations underlie a specific subtype of ALS and enable a careful stratification of newly diagnosed FUS -ALS cases for clinical course and potential therapeutic windows. This will be crucial in the light of incoming gene-specific therapy., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)