Clinical features of anti-mGluR5 encephalitis and comparison according to MRI positivity: a systematic review and analysis

Background Anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare autoimmune neurological disorder with high clinical heterogeneity. The phenotypic spectrum of anti-mGluR5 autoimmune encephalitis (AE) and the relationship between MRI findings and clinical presentations remain to be fully elucidated. Methods Previously reported cases were systematically identified through a literature search of PubMed/MEDLINE, Web of Science and Scopus following PRISMA guidelines. Clinical data from eligible cases, including one from our center, were extracted and analyzed. Patients with a predominant encephalitic phenotype were further stratified into MRI-negative and MRI-positive groups, and statistical comparisons were performed. Results 60 patients were identified, including 40 patients with a predominant AE phenotype. Among the anti-mGluR5 AE patients, common manifestations included cognitive deficits, behavioral and mood disturbances, sleep disturbances, seizures, movement disorders and decreased level of consciousness (dLOC). Tumors occurred in 25.0% of patients, with a higher frequency in Western than Chinese patients (60.0% vs. 4.0%; p 0.001). Brain MRI abnormalities were observed in 52.5% patients, and no significant differences in mRS was observed between MRI-positive and MRI-negative patients. Cerebrospinal fluid (CSF) positivity for anti-mGluR5 antibodies was lower than serum positivity (54.8% vs. 96.8%; p 0.001). Exploratory analyses suggested cognitive deficits tended to be more frequent in MRI-positive than MRI-negative patients (95.2% vs. 68.4%; p = 0.040). CSF pleocytosis was relatively more common in the MRI-positive group, while sleep disturbances, seizures, dLOC, prodromal symptoms, CSF Oligoclonal bands (OCBs) tended to occur more frequently in the MRI-negative group, though not statistically significant. Conclusions The clinical features of anti-mGluR5 AE are heterogeneous. Chinese patients show lower tumor association. Serum antibody testing may be prioritized over CSF testing for diagnosis in suspected anti-mGluR5 patients. MRI abnormalities are observed in approximately half of patients and may not correlate with mRS. Cognitive deficits tend to be more frequent in MRI-positive patients; whereas several other manifestations showed trends, without reaching statistical significance. These observations may suggest hypothesis-generating patterns warranting confirmation.