Sensory nerve action potential amplitudes decreased as patients aged in a cohort of spinal muscular atrophy (SMA) type 1 patients compared with a healthy, age-matched control group.
Spinal muscular atrophy type 1 (SMA1) is a progressive neurodegenerative disorder that leads to motor neuron degeneration and subsequent muscle weakness and atrophy in pediatric patients. While researchers have gained a better understanding of SMA in recent years, the age of sensory neuropathy onset in pediatric patients is still unknown. A study published in Muscle and Nerve aimed to assess sensory nerve conduction velocities (SNCVs) and sensory nerve action potential (SNAP) amplitudes in nerves of patients with SMA1 versus those in healthy subjects.
Despite the development of disease-modifying therapy, longer life expectancy, and increased understanding of SMA—an inherited disease caused by mutation or deletion of the survival motor neuron 1 gene (SMN1)—it is still unknown whether sensory neuropathy in SMA1 is an age- or length-dependent process, the authors noted. Patients with SMA1 typically do not live past 18 months of age.
The study cohort included 28 patients with SMA1 who had 2 copies of the SMN2 gene. Three had subtype 1a, 16 had 1b, and 9 had type 1c. Mean age was 6.73 ± 4.3 years, and the heathy cohort had 93 total participants with an average age of 7.03 ± 4.9 years. Seventeen SMA patients required tracheostomy at the time of the sensory nerve conduction studies, 8 required nocturnal ventilation, and 3 did not require respiratory support.
SNAPs from the right sural and median nerves were recorded, except in the rural nerves of 2 patients (both 12 years of age) and the median and rural nerves of 2 additional patients (ages 14 and 16).
Median nerve SNAP was gauged by a ring electrode on the second phalanx of the third finger performing antidromic stimulation of the nerve at the wrist. Sural SNAP was recorded by 2 electrodes placed below the lateral malleolus, stimulating over the calf lateral to the midline. An average of approximately 30 responses was evoked by supramaximal stimulation of the sensory nerve, and SNCV was measured using the SNAP onset latency.
In the 6-24 months and 3-6 years subgroups, there were no statistically significant differences between children with SMA1 and the healthy control groups. In the 7-16 years cohort, SNAP amplitude was significantly lower in patients with SMA1 than in the healthy control cohort for both the median and sural nerves. There was also a lower SNCV in the rural nerve of SMA1 patients compared with the control group.
The findings point to a correlation between age and axonal sensory neuropathy in patients with SMA1. Compared with external references, SMA1 patients had nerve amplitude within normal range until 6 years of age, with a decline occurring in older children. Nerve velocity decreased beginning at 3 years of age. Five patients also showed an abnormal sensory conduction velocity.
The results, which show axonal sensory neuropathy, are also consistent with findings from mouse model studies of SMA. However, the small sample size of older patients is a limitation in this study. In patients with tracheostomy, it is also unclear whether sensory nerve abnormalities were due to SMA itself or were secondary to ICU complications, the authors noted.
Overall, the authors suggest that monitoring SNAP amplitude may provide more information on the evolution of SMA in general.
“The neurophysiological assessment of the peripheral somatosensory system should be included in the evaluation of patients with SMA1,” the authors wrote. “This could aid the development of new therapeutic strategies that will benefit and support all SMA patients.”
Pro S, Tozzi AE, D'Amico A, et al. Age-related sensory neuropathy in patients with spinal muscular atrophy type 1. Muscle Nerve. Published online August 23, 2021. doi:10.1002/mus.27389