Sensory Nerve Action Potential Analysis in a Cohort of Patients With Spinal Muscular Atrophy Aged 12 Years and Older.

Abstract

Introduction/aims: Survival Motor Neuron 1 (SMN1)-related spinal muscular atrophy (SMA) is characterized by α-motor neuron degeneration, with sensory function assumed to be clinically preserved. However, recent studies in severely affected patients and animal models have challenged this view. Therefore, we assessed the maximum sensory nerve action potential (SNAP) amplitude of the median nerve in patients with SMA and examined its changes during treatment with SMN-splicing modifying therapies.

Methods: We longitudinally assessed median nerve maximum SNAPs in 103 genetically confirmed patients with SMA (types 1c-4, aged ≥ 12 years) before and approximately 1 year after treatment with nusinersen or risdiplam. For comparison, we included 53 age- and sex-matched healthy controls, using identical settings. We also compared data with reference values from a previously published cohort.

Results: Maximum SNAPs were abnormal in 6 patients with SMA (6%), which was comparable to controls (8%), even when corrected for age. In patients younger than 50 years, abnormal maximum SNAPs were more prevalent in patients with SMA types 1 and 2. Maximum SNAPs were higher in SMA compared with controls. Maximum SNAPs showed an age-related decline in most cohorts, but the decline was steeper in patients with SMA type 1c. There was no difference in SNAPs after 1 year of treatment.

Discussion: Our findings suggest the preserved sensory integrity of the median nerve in the majority of patients with SMA (94%), even in longstanding disease. The resilience of sensory neurons of the median nerve, and whether this extends to other peripheral nerves, warrants further investigation.

Trial registration: The study was approved by the local medical ethics committee (no. 20-143) and registered in the Dutch registry for clinical studies and trials (www.toetsingonline.nl-NL72562.041.20, March 26, 2020).