Anti-mGluR1 encephalitis is associated with autoantibodies against neuronal mGluR1 and manifests as cerebellar ataxia, although the full clinical spectrum is unknown. Response to immunotherapy is variable; it is unclear why some patients improve and others are left with long-term neurological deficits. Previous studies with a mice model and cerebellar slices suggested that mGluR1 antibodies are pathogenic, but the molecular mechanisms remain unclear.

We reviewed the clinical information of newly identified and previously reported patients. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 were examined in cultured neurons.

We identified 11 new patients (10 adults, 1 child), 7 males. All patients and 19 previously reported cases (n=30, median age 55) developed a subacute cerebellar ataxia that was associated with behavioral/cognitive changes or other neurological symptoms in 25 of them (86%), and with a tumor in 3/26 (11%). Twelve/19 (63%) patients had normal MRI at onset, and 10/12 (83%) developed cerebellar atrophy at follow-up. Twenty-five/30 (83%) patients received immunotherapy. After a median follow-up of 2 years, 13/25 (52%) had clinical stabilization, 10/25 (40%) significantly improved, and 2/25 (8%) died. Patients with bad outcome (mRS>2, n=7) had higher degree of initial disability, as reflected by the need of assistance to walk (p<0.01) and a worse SARA (Scale for Assessment and Rating of Ataxia) score (p<0.05).  Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in neurons.

Anti-mGluR1 encephalitis associates with severe cerebellar ataxia and patients are at risk of developing long-term disability and cerebellar atrophy. The antibodies are pathogenic by decreasing synaptic mGluR1 clusters.