To highlight a case of concurrent anti-SJ/ITPR1 and anti-NMDA encephalitis.

The anti-Sj/inositol 1,4,5-trisphosphate receptor (ITPR1) has been associated with autoimmune cerebellar ataxia and malignancy. Reports of patients with anti-Sj/ITPR1 describe isolated cerebellar ataxia as well as various manifestations throughout the central and peripheral nervous system. Anti-NMDA encephalitis presents with subacute decline, seizures, movement disorder, alterations in behavior and cognition, autonomic dysfunction, and central hypoventilation but is rarely associated with cerebellar ataxia in adults.

A 28-year-old female with no relevant medical history presented to an outside hospital with acute onset headache, diplopia, nystagmus, and vertigo. MRI and MRV were unremarkable. CSF analysis showed a lymphocytic pleocytosis. She was empirically treated with acyclovir, although viral serologies were negative. On initial assessment in our clinic, neurologic exam showed square wave jerks, ataxic eye movements, resting tremor, appendicular and gait ataxia. She progressively declined with gait instability, autonomic dysfunction, neuropsychiatric symptoms, and significant weight gain from compulsive hyperphagia. Her course was complicated by respiratory failure and tracheostomy was placed for mechanical ventilation. Malignancy screening with mammogram, CT, and full body PET was negative. Transvaginal ultrasound was nondiagnostic. Serum paraneoplastic autoantibody panel was negative. EEG showed severe generalized slowing. Repeat CSF studies were positive for anti-SJ/ITPR1 and anti-NMDA. She was treated with high-dose IV methylprednisolone, plasmapheresis, and rituximab. She has residual moderate/severe ataxia, but is now conversant, without trach dependence, and ambulates with assistance.

There is no definite current evidence for the pathogenicity of the ITPR1 antibody. Given the rarity of cerebellar ataxia in anti-NMDA encephalitis in adults, one could argue for a pathogenic role of ITPR1 in our case. No underlying malignancy was identified in our patient. We will continue surveillance since the clinical syndrome may precede tumor identification by several years.