• Taha Bali, Wade Self, Jingxia Liu, Teepu Siddique, Leo H Wang, Thomas D Bird, Elena Ratti, Nazem Atassi, Kevin B Boylan, Jonathan D Glass, Nicholas J Maragakis, James B Caress, Leo F McCluskey, Stanley H Appel, James P Wymer, Summer Gibson, Lorne Zinman, Tahseen Mozaffar, Brian Callaghan, April L McVey, Jennifer Jockel-Balsarotti, Peggy Allred, Elena R Fisher, Glenn Lopate, Alan Pestronk, Merit E Cudkowicz, and Timothy M Miller.
• Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
• J. Neurol. Neurosurg. Psychiatr. 2017 Feb 1; 88 (2): 99-105.

ImportanceUnderstanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population.ObjectiveTo establish an updated natural history of ALSSOD1.Design, Setting And ParticipantsRetrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000.Main Outcomes And MeasuresAge of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis.ResultsMean age of disease onset was 49.7±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p<0.0001, log-rank). A statistically significant increase in ALS-FRS decline in SOD1A4V compared with SOD1non-A4V participants (p=0.02) was observed, as well as a statistically significant increase in ALS-forced vital capacity decline in SOD1A4V compared with SOD1non-A4V (p=0.02).Conclusions And RelevanceSOD1A4V is an aggressive, but relatively homogeneous form of ALS. These SOD1-specific ALS natural history data will be important for the design and implementation of clinical trials in the ALSSOD1 patient population.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

34 keywords...

hide…