Primary lateral sclerosis in Brazil: phenotypic heterogeneity, non-motor features, and prognostic markers in a 17-year multicentre cohort.

Objective

Primary lateral sclerosis (PLS) is a rare upper motor neuron disorder within the motor neuron disease spectrum. Data from Latin America remains limited. We aimed to characterize clinical phenotypes, non-motor features, and prognostic markers in a systematically adjudicated Brazilian PLS cohort.

Methods

In this retrospective multicenter study, we analyzed the data of 81 patients meeting the Turner 2020 criteria for probable/definite PLS at SARAH Network Hospitals (2007-2023). Clinical phenotyping, neurophysiology, C9orf72 testing, and survival analyses were conducted.

Results

The participants' median age at onset was 54 years (interquartile range 46-62); 53% of them were men. The onset distribution was as follows: lower limb 65%, bulbar 22%, and upper limb 11%. Extrapyramidal signs (7%) identified high-risk patients with fourfold increased mortality (relative risk [RR] 4.2, p = 0.013) and sixfold increased cognitive impairment (RR 6.3, p = 0.007). Eight patients (9.9%) exhibited hemiparetic presentations, with two meeting the definite Mills syndrome criteria; seven patients progressed to generalized PLS. Non-motor features were common: pseudobulbar affect (51%), urinary urgency (57%), and cognitive impairment (11%). Family history was observed in 10% and C9orf72 expansion in 3%, with intrafamilial phenotypic variability. Five-year survival was excellent (98%) without onset-site effect (hazard ratio 0.80, p = 0.697). Two patients maintained isolated corticobulbar syndrome for 50-71 months.

Conclusions

This first Latin American PLS cohort demonstrates clinical characteristics comparable to those reported in international studies. Extrapyramidal signs emerged as a high-risk marker. Hemiparetic presentations appear transitional, and non-motor manifestations support PLS as a multisystem disorder.