To report a case of metabotropic glutamate receptor type 1 (mGluR1) antibody syndrome presenting with ataxia and severe ophthalmoplegia.

The mGluR1 antibody syndromes are rare disorders presenting with subacute ataxia and varying nystagmus, altered saccadic eye movements, and encephalopathy. While diplopia has been described with this syndrome, near-complete external ophthalmoplegia has not.  The classic Miller Fisher syndrome (MFS) triad of ataxia, areflexia, and ophthalmoplegia is not always present and patients can display isolated ophthalmoplegia and ataxia without areflexia.  In this setting, differentiating between the mGluR1 antibody syndrome and MFS can be difficult.

A 66-year-old otherwise healthy male presented with subacute onset of ataxia, dysarthria, and progressive diplopia. His examination showed normal mentation, limited vertical and lateral gaze, left hypertropia, gaze-evoked nystagmus, flaccid dysarthria, and dysmetria and titubation. Muscle reflexes were symmetrically reduced in upper extremities but normal in lower extremities. Head CT/CTA and MRI were normal and an evaluation for other etiologies was unremarkable. CSF showed 11 nucleated cells (90% lymph/10% mono) but was otherwise normal. Mayo Clinic paraneoplastic panel and GQ1b antibodies were sent and he was treated with 2 grams/kg IVIg with partial improvement in ataxia and extraocular movements. Subsequently, GQ1b antibody was negative but mGluR1 antibody IFA titer was abnormal at 1:1920 (normal < 1:240). Work-up for occult malignancy was negative and monthly IVIg was continued. At 3-month follow-up he has compete resolution of extraocular movements and partial improvement in ataxia, dysmetria, and gaze-evoked nystagmus.

1. The mGluR1 antibody encephalitis is a rare central disorder that can be clinically indistinguishable from MFS variants.

2. Early detection is important as mGluR1 syndromes may be associated with underlying malignancy (lymphoma, prostate, leukemia, and testicular cancer).

3. Initial treatment for the mGluR1 antibody syndromes includes IVIg, plasma exchange, and IV steroids whereas MFS is typically refractory to IVIg.