Peripheral neuropathy in neuronal intranuclear inclusion disease: a clinical and electrophysiological cross-sectional study.

Background And Objective: Neuronal intranuclear inclusion disease (NIID) is a multifaceted disorder impacting both the central and peripheral nervous systems. This study aims to investigate the clinical and electrophysiological characteristics of peripheral neuropathy in patients with NIID.

Methods: In this cross-sectional study, patients diagnosed with NIID were prospectively recruited from multiple centers across China between October 2017 and May 2024. Comprehensive neurological examinations, brain magnetic resonance imaging, and NOTCH2NLC gene analysis were performed. All participants underwent electrophysiological evaluations, which encompassed nerve conduction studies, F-wave studies, and needle electromyography.

Results: This analysis included a total of 78 patients diagnosed with NIID, with a mean age of 61.0 ± 9.9 years, of whom 60.2% were female. Among these patients, 85.9% exhibited peripheral neuropathy. Specifically, 19 patients (24.4%) presented with symptomatic peripheral neuropathy, with 17 of these individuals demonstrating sensorimotor polyneuropathy. Additionally, 48 patients (61.5%) exhibited subclinical peripheral nerve damage. Segmental motor conduction studies indicated that both distal and proximal nerve segments were uniformly affected. F-wave latency prolongation was observed in 84.6% of tibial nerves, demonstrating high sensitivity (66/67) and specificity (11/11) for detecting peripheral neuropathy in NIID. The severity of peripheral neuropathy was stratified into four levels, with approximately two-thirds of cases presenting with pure demyelination and one-third displaying a combination of demyelination and axonal degeneration. Severe axonal damage was exclusively identified in the neuromuscular disease-dominant subtype of NIID. Importantly, male patients exhibited more pronounced peripheral nerve damage compared to female patients.

Conclusions: This study identified a significant prevalence of peripheral neuropathy in NIID, exhibiting a spectrum of severity ranging from mild demyelination to severe axonal damage. Prolongation of F-wave latency emerged as a sensitive marker for the detection of peripheral nerve impairment. Furthermore, the findings underscore the potential influence of gender in the pathophysiology of NIID, warranting further investigation.