1447 A Rare but Fatal Case of N-methyl-D-aspartate Receptor Antibody Encephalitis Associated With a Pancreatic Neuroendocrine Tumor

Abstract

INTRODUCTION: N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is an autoimmune inflammatory condition of the brain thought to be paraneoplastic given its strong association with malignancy, but such related tumors are rarely detected in older males. To our knowledge, there is only a single case report of NMDAR-Ab encephalitis related to a pancreatic neuroendocrine tumor (NET). Here, we report a case of NMDAR-Ab encephalitis associated with pancreatic NET that was fatal despite early tumor resection. CASE DESCRIPTION/METHODS: A 79-year-old man with hypertension presented with acute onset of confusion, agitation, and urinary and bowel incontinence. He was living independently but had progressive short-term memory loss over the year prior. Electroencephalogram showed diffuse slowing without seizure activity. Magnetic resonance imaging of the brain noted trace sulcal FLAIR hyperintensity in perirolandic regions. Cerebrospinal fluid (CSF) analysis revealed elevated protein (96 mg/dL), low nucleated cell count, no oligoclonal bands, and negative infectious serology and cultures. CSF paraneoplastic panel was positive for anti-NR1 antibody, confirming the diagnosis of NMDAR-Ab encephalitis. Malignancy workup revealed a 1.2 cm mass in the pancreatic tail, and endoscopic ultrasound-guided fine-needle biopsy showed positive staining for synaptophysin and chromogranin A consistent with a well-differentiated NET. The patient rapidly declined from worsening encephalopathy and required percutaneous gastrostomy tube placement. He underwent laparoscopic distal pancreatectomy and splenectomy with intravenous immunoglobulin and glucocorticoids, but a repeat CT abdomen next month showed peritoneal metastases with diffuse uptake on somatostatin receptor scintigraphy and rising serum chromogranin A (603 ng/mL). He had no significant neurologic recovery and eventually died on comfort measures without further interventions. DISCUSSION: Though rare, prior cases of NMDAR-Ab encephalitis associated with NET described the importance of early surgical removal of the underlying tumor to provide the best chance of neurologic recovery. Metastatic disease portends a poor prognosis as it renders encephalitis impossible to resolve. Worldwide experience with NMDAR-Ab encephalitis is limited and further observations are needed to refine current treatment strategies.