Temperature-induced symptoms in adolescents and adults with spinal muscular atrophy

INTRODUCTION: Temperature-induced aggravation of weakness is a well-known characteristic of demyelinating and motor neuron disorders. We investigated prevalence, frequency, and severity of symptoms during heat and cold exposure in patients with 5q-spinal muscular atrophy (SMA).

METHODS: We conducted a longitudinal cohort study systematically assessing temperature-induced symptoms by means of a standardized questionnaire at baseline and after one year in adolescents and adults with SMA types 1-4 and age-matched healthy and disease controls. All patients were treatment-naïve for SMN-augmenting therapies at baseline.

RESULTS: We included 103 patients with SMA types 1-4 (median age 39 years, range 13-67 years), 25 healthy controls and 46 disease controls. Eighty-four (82%) patients with SMA and 24 (52%) disease controls were non-ambulatory. Ninety patients with SMA (87%) reported cold-induced symptoms, primarily as aggravation of weakness (85%, n = 88), i.e., cold paresis. Cold paresis was more prevalent in non-ambulatory patients with SMA (94% vs. 47%) and associated with lower Revised Upper Limb Module (RULM) scores in these patients. Healthy controls did not report cold-induced symptoms, in contrast to the 30 (65%) disease controls who did experience cold paresis. Cold paresis was more prevalent in non-ambulatory patients with SMA compared to disease controls. The prevalence of cold paresis was unchanged after one year of disease-modifying treatment.

CONCLUSIONS: Cold paresis is commonly experienced by patients with SMA, particularly those with more severe weakness based on SMA type, ambulatory status, and RULM score. Better understanding of the underlying mechanisms of cold paresis might lead to new symptomatic treatment to preserve motor functionality.Trial registration information: NL72562.041.20 (registered at www.toetsingonline.nl; 26-03-2020).