CASPR2 antibody-associated peripheral nerve hyperexcitability presenting with neuropathic pain and insomnia

Abstract

Contactin-Associated Protein-like 2 (CASPR2) antibody-associated disorders present with a wide range of clinical features, including peripheral nerve hyperexcitability (PNH), neuropathic pain, autonomic dysfunction, and central nervous system involvement such as insomnia or encephalopathy. While immunotherapy is frequently required, spontaneous clinical improvement has been reported in a small subset of patients. The clinical presentation may vary considerably, and electrophysiological findings often play a key role in diagnosis. A 49-year-old man presented with burning pain and paresthesia affecting the hands and forearms, followed by similar symptoms in the lower extremities and deep aching pain in the thighs. Severe insomnia and mild autonomic symptoms, including diarrhea and hyperhidrosis, were also present. Neurological examination revealed distal paresthesia in a glove-and-stocking distribution. Routine laboratory investigations were unremarkable. Nerve conduction studies were within normal limits; however, low-amplitude after-discharges were observed following tibial M-wave responses. F-wave recordings demonstrated prominent after-discharges, particularly in the tibial and median nerves. Similar abnormalities were detected during low-frequency repetitive nerve stimulation. Needle electromyography revealed fasciculations, rare myokymic discharges, and increased insertional activity limited to the paraspinal muscles. Serum testing confirmed CASPR2 antibody positivity. Brain MRI, sleep EEG, and malignancy screening showed no abnormalities. By day 40, the patient experienced near-complete clinical recovery without immunotherapy, although electrophysiological abnormalities remained detectable. Oral prednisolone was subsequently initiated to reduce the risk of relapse. This case emphasizes the clinical heterogeneity of CASPR2-associated syndromes and suggests that spontaneous clinical improvement may occur even when electrophysiological findings have not fully normalized.