LAUSR

A 65-year-old man presented with a 3-month history of gait disturbance, generalized chorea, and painful intermittent cervical dystonia. He also reported sleep disruption, mood changes, and irritability. He had a medical history of hypertension and polymyalgia rheumatica. There was no family history. Neurological examination evidenced moderate generalized chorea, dystonia of the neck, mild unsteady gait, and subtle dysarthria. There were no signs of parkinsonism or limitation of eye movements. Also, no Kayser-Fleischer ring, xanthomas, or signs of neuropathy were observed. A neuropsychiatric assessment evidenced emotional lability with no neurocognitive impairment. A blood test showed normal iron profile, cholestanol, phytanic acid levels, vitamin E, copper, ceruloplasmin, creatine kinase, chitotriosidase activity, hypercoagulability, systemic autoimmunity assays, and peripheral blood smear examination. HIV and bacterial serologies were negative. Genetic testing excluded both Huntington’s disease and the main Huntington’s disease-like spinocerebellar ataxia 17. A brain MRI showed paramagnetic deposits in the basal ganglia, substantia nigra, and red nucleus (Fig. 1A,D). A normal CT of the brain (Fig. 1C,F) ruled out calcification. A video-polysomnography showed fragmented sleep, motor restlessness, vocalizations, the absence of REM-sleep, and an apnea-hypopnea index of 57 (severe sleep apnea). Symptomatic treatment with tetrabenazine, quetiapine, trazodone, and CPAP was started. Nine months later, the patient’s clinical state was suddenly impaired by an exacerbation with bulbar dysfunction (severe dysarthria, dysphagia, and aspiration pneumonia) and severe gait instability. Due to this impairment, the patient was admitted to our hospital. A lumbar puncture showed CSF pleocytosis (9 cells per mm, 100% lymphocytes). Oligoclonal bands were negative. An autoimmune etiology of the disorder was suspected. After intravenous methylprednisolone pulses (250 mg per day for three days), the patient improved to his baseline. A total body CT was normal. At this time, a control MRI revealed an increase of paramagnetic deposits (Fig. 1B,E). AntiGAD, antiIA2, and a panel of antibodies against neuronal cell-surface antigens (NMDAR, AMPAR, CASPR2, LGI1, DPPX, and GABAB) were negative in serum and CSF. Anti-IgLON5 antibodies were specifically assessed, obtaining a positive result in serum and CSF (Fig. 2). HLA-DQB1*0501 and HLA-DRB1*10:01 alleles were present. Anti-IgLON5 encephalopathy was diagnosed. In addition to symptomatic treatment, rituximab was started as maintenance immunosuppressive therapy. At present, four years after disease onset, the patient remains stable (slight dysarthria and mild chorea persist) with no new exacerbation.