Neurexin-3α IgG-mediated autoimmune encephalitis with psychiatric manifestations and choreiform movements: a case report and literature review

Abstract

To summarize the clinical manifestations, ancillary examination findings, treatment course, and prognosis of a patient with neurexin-3α IgG-mediated autoimmune encephalitis presenting with prominent psychiatric disturbances and choreiform movements, and to review the literature on the clinical spectrum of this disease. A 52-year-old woman with a history of hypertension and biopsy-proven podocytopathy with a “full-house” immunofluorescence pattern showing diffuse positivity for IgG, IgA, IgM, C3, and C1q, diagnosed in February 2026; however, a definitive diagnosis of lupus podocytopathy remained uncertain, as the patient lacked systemic lupus erythematosus manifestations. She was admitted on April 3, 2026, with a 5-day history of psychiatric disturbances and involuntary choreiform movements in all four limbs, preceded by significant psychological stress (bereavement). Neurological examination revealed slowed responses and impaired calculation. Cranial MRI showed only bilateral periventricular small ischemic foci (Fazekas grade 1) with normal SWI. Initial EEG demonstrated sharp waves and spike-and-wave complexes in the left parietal, occipital, and temporal regions. CSF analysis revealed leukocytosis (21/μl, 90% mononuclear cells), protein of 0.4 g/L, elevated IgG index of 0.76, and elevated 24-hour intrathecal IgG synthesis rate of 5.63 mg/dl. CSF mNGS detected 453 EBV sequences (RPM) with a relative abundance of 97.48%. Serum EBV VCA-IgG and EBNA-IgG were elevated with negative IgM. Autoantibody testing followed a stepwise approach: initial screening for conventional autoimmune encephalitis, paraneoplastic, and demyelinating antibodies was negative; subsequent tissue-based assay (TBA) of CSF revealed strong positive immunoreactivity, prompting expanded antibody panel testing, which ultimately detected anti-neurexin-3α antibodies in serum (titer 1:30) and CSF (titer 1:100), confirmed by both cell-based assay (CBA) and TBA. The patient’s condition progressively deteriorated, requiring endotracheal intubation on April 21 and tracheostomy on April 30. She received methylprednisolone pulse therapy at 500 mg/day for 5 days followed by a stepwise taper, intravenous immunoglobulin at 0.4 g/kg for 5 days, and five sessions of plasma exchange from April 30 to May 8 due to poor initial response. Choreiform movements gradually resolved after plasma exchange. She was weaned from mechanical ventilation on May 19 and decannulated on May 27. During the ICU course, she developed pulmonary infection with carbapenem-resistant Acinetobacter baumannii, which was controlled after antibiotic adjustment. Repeat EEG normalized on June 1. She was discharged from rehabilitation on June 9 on oral methylprednisolone 32 mg/day. On June 26, 2026, follow-up serum TBA showed weakly positive immunoreactivity, with the serum antibody titer remaining at 1:30. She subsequently received four infusions of efgartigimod at 400 mg each for consolidation immunotherapy and was transitioned to ofatumumab for long-term maintenance. At follow-up on August 6, 2026, the patient had no residual psychiatric symptoms or choreiform movements, with muscle strength recovered to 4+ in all limbs, full independence in daily activities, ambulation without assistance, and only mild gait instability. Neurexin-3α IgG-mediated autoimmune encephalitis is a rare but treatable condition. Choreiform movements expand its clinical spectrum. The coexistence of podocytopathy raises a hypothesis of shared antigenicity between renal and neuronal neurexin family members, though this remains purely speculative. CSF EBV reactivation may represent a bystander phenomenon or epiphenomenon of severe immune dysregulation rather than a confirmed trigger. Tissue-based assay provides crucial diagnostic direction when conventional screening is negative. Early recognition, comprehensive immunotherapy, and meticulous ICU management are important determinants of favorable outcomes. Given the inherent limitations of a single case report, these findings warrant confirmation through larger cohort studies.