Peripheral nervous system involvement accompanies central nervous system involvement in anti-N-methyl-D-aspartate...

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis, primarily affecting the central nervous system (CNS) and typically presenting with neuropsychiatric symptoms. However, emerging evidence suggests that peripheral nervous system (PNS) involvement may also occur in some cases.

To investigate the clinical and neuro-electrophysiological characteristics of PNS involvement in patients with positive anti-NMDAR antibodies in cerebrospinal fluid (CSF).

We retrospectively reviewed all patients with CSF-confirmed anti-NMDAR encephalitis at the Second Affiliated Hospital of Guangzhou Medical University between 2016 and 2025. Collected data included initial symptoms and disease severity, CSF and serum test results, magnetic resonance imaging (MRI) and neuro-electrophysiological findings, primary treatment regimens, presence of coexisting autoimmune disorders, and clinical outcomes.

Among the 46 patients with anti-NMDAR encephalitis, 9 patients (19.6%) exhibited PNS involvement. The average age of onset in this subgroup with PNS involvement were significantly older than those with CNS involvement only (mean ± SD: 36.2 ± 18.9 years vs. 24.6 ± 12.4 years; P = 0.029). Limb weakness was significantly more frequent in the PNS involvement group (55.6% vs. 2.7%; P < 0.001). Electromyography (EMG) was performed in 18 patients (39.1%), of whom 10 patients (55.6%) showed abnormal findings. Among these, 1 patient exhibited active radiculopathy associated with motor neuron disease, 2 patients had isolated radiculopathy, and 1 patient presented with mixed polyneuropathy involving both motor and sensory functions. Cranial nerve involvement was observed in 2 patients (22.2%). In one case, PNS involvement was the initial symptom. All patients received first-line immunotherapy. PNS involvement was not significantly associated with disease prognosis.

PNS involvement in anti-NMDAR encephalitis is not uncommon and most frequently manifests as acute or subacute limb weakness. Neuro- electrophysiological abnormalities predominantly involve motor conduction pathways and proximal nerve roots. This is a single-center retrospective study with a small sample size. Large-sample prospective studies are needed to further validate the findings.