Successful Management of Anti‐mGluR1 Encephalitis with Immunosuppressive Treatment: Dengue Virus as a Trigger?

Abstract

A case of reversible myoclonus-ataxia related to anti-metabotropic glutamate receptor 1 (mGluR1) autoantibodies (mGluR1-Ab), using high-dose steroid and intravenous (IV) immunoglobulin infusions, was recently reported. Patients with mGluR1-Ab are highly rare, and the prognosis is not well known. We observed a significant recovery in a woman with mGluR1-Ab, suggesting the interest of immunomodulatory treatments. In April 2018, a 22-year-old woman was admitted to the University Hospital of Guadeloupe with ataxia. One month before she complained about coughing but no fever, no rash, and no coryza symptoms. Five days before admission, she had temporal headaches. The neurological examination was normal. During the next 5 days, she progressively developed dizziness, walking disability, and dysarthria. On admission, she had a severe cerebellar syndrome with severe gait, limbs and trunk ataxia, dysarthria, hypotonia, areflexia, action tremor, continuous horizontal nystagmus, and oscillopsia. International Cooperative Ataxia Rating Scale (ICARS) score was 80/100, and modified Rankin Scale score (mRS) was 5. Laboratory analysis showed raised leucocytes (33 × 10/L), polymorphonuclear leucocytes (30.36 × 10/L), and C-reactive protein (92 mg/L, normal <10 mg/L). The day after admission, she developed visual and auditory hallucinations. Electroencephalogram showed a slowing of the left hemisphere and triphasic frontal spikes. Brain magnetic resonance imaging showed cerebellar leptomeningeal contrast enhancement. Cerebrospinal fluid (CSF) was purely lymphocytic (214 × 10/L) with a protein level at 42 mg/dL and positive oligoclonal bands. Thoracic and abdominal computed tomography scans were normal. Cognitive and psychiatric evaluations at day 5 showed moderate dysexecutive and attentional dysfunction, phasic and mnesic disorders, and mild depression. High levels of antidengue antibodies were detected in serum (immunoglobulin G (IgG) 33.93; immunoglobulin M (IgM) 17.06 NovaTec-Units (NTU); normal <9 NTU). Dengue nonstructural protein 1 (NS1) antigen was negative. mGluR1-Ab were detected in blood and CSF by immunohistochemistry and cell-based assay (French reference center). The patient received 3 monthly IV immunoglobulin infusions. After 1 month, brain magnetic resonance imaging and CSF analysis became normal. A partial clinical improvement (ICARS 34/100, mRS 4) justified the introduction of cyclophosphamide (1 g IV once, and 0.5 g monthly 5 times) and rituximab (1 g IV twice, delay 15 days) 6 months after the disease onset. The patient was able to walk unaided 2 months later (ICARS 24/100, mRS 2). Whole-body PET/CT showed no tumor, but a cerebellar, cingulate, and prefrontal hypometabolism (Fig. 1). At 1 year after the disease onset, neurological examination showed an imperfect tandem gait testing and inconspicuous kinetic cerebellar ataxia (ICARS 11/100, mRS 1; Video 1). Our new case of ataxia and mGluR1-Ab associated with seizures, cognitive, and psychiatric symptoms also showed a clear cerebellar hypometabolism. The presence of Dengue virus (DENV) IgM suggested a possible postinfectious mechanism and raised the question of arboviral infection and, specifically, DENV infection as a trigger of autoimmune encephalitis. As reported recently, intensive therapy allowed a remarkable improvement, whereas IV immunoglobulin infusions were moderately active. Our case report, underlines that ataxia with mGluR1-Ab must be quickly and intensively treated with immunomodulators to improve functional prognosis and potentially cure the patient.