Introduction

ITPR-1 (Inositol 1,4,5-Trisphosphate Receptor Type 1) autoimmunity is a recently described entity, with the predominant manifestations described thus far including cerebellar ataxia and peripheral neuropathy. Here, we describe the first case of  paraneoplastic encephalopathy related to ITPR1 antibody, associated with lymphoma.

Case Presentation

An 80-year-old man with hypertension and benign prostatic hypertrophy presented with progressive disorientation, inattention, perseveration, fatigue, and weight loss, over 2 months. He was previously functionally independent, however required significant family assistance after symptom onset.

Initial neurologic examination was notable for profound disorientation, inattention, impaired comprehension and perseveration. Preliminary laboratory results revealed hyponatremia and raised CRP. CT CAP showed extensive lymphadenopathy and splenomegaly. MRI brain revealed global atrophy. EEG revealed theta background slowing. Cervical node biopsy yielded anaplastic large cell lymphoma.  He commenced BV-CHP (Brentuximab + Cyclophosphamide + Doxorubicin + Prednisone).

His CSF autoimmune panel yielded an antibody reactive against cerebral tissue, which was demonstrated to be ITPR1 antibody on immunofluorescence and cell-based assays. He received 5 days of IVIG. His mental status improved significantly during hospitalization. He has since completed 6 cycles of BV-CHP. CT PET has demonstrated resolution of FDG avid adenopathy.  Upon 3 month follow up, examination revealed ongoing improvement of mental status, near cognitive baseline.

Of the 19 ITPR1 antibody patients with data, cancer was reported in 7; including 1 renal cell carcinoma, 2 lung carcinomas, 3 breast carcinomas; 1 with concurrent endometrial carcinoma and 1 multiple myeloma. Manifestations include 10 cases of ataxia, 7 cases of neuropathy, 2 cases of encephalopathy with seizure, in addition to cervical dystonia and spastic paraparesis. There is, thus, established heterogeneity in the manifestations of ITPR1 autoimmunity. We report this case to add to the phenotypic descriptions of ITPR1 autoimmunity, report a novel association with lymphoma and highlight clinical improvement with immunotherapy and chemotherapy.