A Systematic Review About Neuropathies in Spinal Muscular Atrophy (SMA): Current Insights and Future Directions.

BACKGROUND

Spinal muscular atrophy (SMA) is primarily a motor neuron disorder, yet peripheral neuropathic features have been variably reported. This systematic review evaluates nerve conduction study (NCS) findings in genetically confirmed 5q-SMA and examines whether neurophysiology can function as a biomarker.

METHODS

Following PRISMA 2020 guidelines and a PROSPERO-registered protocol, PubMed, Embase and Scopus were searched through November 2025. Original studies reporting NCS in SMN1-confirmed SMA were included. Data on neuropathy patterns, SMN1/SMN2 status and treatment exposure were extracted. Study quality was assessed using Joanna Briggs Institute tools.

RESULTS

Twenty-three studies including 395 patients were identified. NCS methodology was heterogeneous, and only 12 studies (52.2%) reported sufficient detail to allow formal classification of neuropathy type. Among these, axonal abnormalities involving motor, sensory or sensorimotor fibers were most frequently reported. Demyelinating features were rare and occurred only in a sensorimotor distribution, often in association with potential alternative or modifying factors. Most longitudinal and treatment-focused studies relied on amplitude-only protocols, limiting assessment of sensory and demyelinating involvement. Longitudinal neurophysiological follow-up was reported in 156 patients, predominantly using compound motor action potential/sensory nerve action potential (CMAP/SNAP) amplitude-only protocols; within these constraints, treated patients were more often stable or improved, while deterioration was rare and observed only in untreated cases.

CONCLUSION

Motor axonal neuropathy is the most consistently detectable neurophysiological abnormality in 5q-SMA, largely reflecting methodological constraints. Longitudinal NCS data, predominantly CMAP-based, may provide supportive information for monitoring treated patients, but standardized and comprehensive NCS protocols are required to define the full spectrum of peripheral nerve involvement.