Clinical spectrum and outcomes of anti-metabotropic glutamate receptor 5 encephalitis in Chinese patients: a case report and literature review

TL;DR

This study examines the clinical features and treatment outcomes of anti-mGluR5 encephalitis in Chinese patients, showing varied symptoms and a low tumor association.

Contribution

The study provides the first detailed clinical overview of anti-mGluR5 encephalitis in a Chinese cohort, emphasizing its low paraneoplastic rate and effective immunotherapy.

Findings

Chinese patients with anti-mGluR5 encephalitis show significant clinical heterogeneity and a low tumor association (17%).

Immunotherapy, including steroids and rituximab, leads to favorable outcomes in most patients.

Both serum and cerebrospinal fluid antibody testing are essential for accurate diagnosis.

Abstract

Anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare autoimmune disorder that targets the metabotropic glutamate receptor. It is frequently linked to limbic encephalitis and paraneoplastic syndromes, such as Ophelia syndrome associated with Hodgkin lymphoma. Due to its rarity, the complete clinical spectrum and regional variations of this condition, particularly among Chinese populations, remain inadequately understood.

We present a case of a 39-year-old Chinese male diagnosed with anti-mGluR5 encephalitis. The patient initially presented with persistent fever, which later progressed to seizures, psychosis, apathy, drowsiness, and memory impairment. Brain imaging findings were unremarkable, while electroencephalogram (EEG) revealed predominant beta wave activity. Cerebrospinal fluid (CSF) analysis showed pleocytosis and elevated protein levels. Both serum and CSF tested strongly positive for mGluR5 antibodies (titers 1:160 and 1:640, respectively), with no other autoantibodies detected. A thorough evaluation revealed no evidence of an underlying tumor. Symptom resolution was rapid following intravenous methylprednisolone pulses, with sustained remission achieved through rituximab therapy combined with a gradual tapering of steroids over one year of follow-up.

In 18 Chinese patients, the median age was 36 years (range 7–60), with 61% being male (11/18). Only 17% (3/18) had associated tumors, including two cases of teratomas and one of gangliocytoma. The clinical manifestations were highly diverse, with headache (44.4%), irritability/sleepiness (38.9%), and seizures (38.9%) being the most prevalent symptoms. Additional symptoms included hallucinations (33.3%), fever (27.8%), memory impairment (27.8%), dystonia (22.2%), and consciousness disorders (22.2%). Antibody analysis showed that 94.4% (17/18) of patients were serum mGluR5-positive, 61.1% (11/18) had mGluR5 antibodies in cerebrospinal fluid, and 55.5% (10/18) tested positive in both. Magnetic resonance imaging (MRI) anomalies were identified in 72.2% of patients, typically affecting the temporal/insular lobes and deep gray matter. Immunotherapy, consisting of steroids, intravenous immunoglobulin and/or immunosuppressive drug, was administered to 94.4% (17/18) of patients, resulting in favorable outcomes for 17 cases.

This study highlights that anti-mGluR5 encephalitis in Chinese patients exhibits significant clinical heterogeneity and a notably low association with tumors (17%), contrasting with higher rates reported elsewhere. Both serum and CSF antibody testing are crucial for diagnosis. Immunotherapy, including steroids and potentially rituximab, appears highly effective. Clinicians should be aware of the broad symptom spectrum and the relatively low paraneoplastic risk in this population. Vigilance for tumors, especially teratomas and neural tumors, remains essential.

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