Case Presentation: Confusion and headache in a young male is suspicious for encephalitis until proven otherwise. We present a case of anti-NMDA receptor encephalitis from clear cell renal cell carcinoma causing acute encephalopathy in a hospitalized patient.
A 25 year old African American male presented with two days of slurred speech, headache and confusion. He was without travel or sick contacts. Physical examination revealed agitation and slurred speech. He was oriented to person, place and time. Chest x-ray and head CT were normal. Labs were unremarkable with a WBC count of 7.35 thousand/uL. UA was normal. LP was done and gram stain showed 5/slide – 2/field gram positive cocci. CSF revealed protein of 29 mg/dL, glucose 58 mg/dL and 43/mm3 nucleated cells with 88% lymphocytes. He was placed on IV acyclovir, ceftriaxone and vancomycin.
Neurology was suspicious for limbic encephalitis given the lack of meningitis. All cultures remained negative. CSF for cryptococcal Ag, West Nile, HSV, enterovirus, cytology, LGI-1 Ab, IgG index and flow cytometry were negative. EEG showed right temporal delta wave slowing concerning for limbic encephalitis. Plasmapheresis was started and symptoms gradually improved. CSF was with 7 oligoclonal bands, positive for N-Methyl-D-Aspartate (NMDA) receptor antibody and a positive autoimmune encephalopathy panel. Anti-NMDA receptor encephalitis was confirmed with this. A CT scan of the abdomen and pelvis revealed a heterogeneous 2.3 cm mass at the upper pole of the right kidney.
Urology was consulted and he required surgery. He continued improvement on plasmapheresis and underwent a right nephrectomy. Pathology showed clear cell renal cell carcinoma with a positive nuclear expression for BRCA1 associated protein-1 (BAP-1). Plasmapheresis was stopped as his mental status returned to baseline. His post-operative course was unremarkable and discharged home.
Discussion: Anti-NMDA receptor encephalitis is an autoimmune encephalitis associated with psychiatric manifestations, seizures, language dysfunction, memory deficits and confusion. These symptoms in the absence of meningitis cause concern for limbic encephalitis, which is a manifestation of autoimmune encephalitis. There is known association with certain ovarian tumors, but rarely in males, especially renal cell carcinoma.
EEG showed right temporal delta wave slowing and CSF with lymphocytic pleocytosis suggests autoimmune encephalitis. To further support this diagnosis, identification of a specific antibody was confirmed. Many patients can be antibody negative. Infection was ruled out and the gram stain was not significant as all cultures remained negative.
Treatment for anti-NMDA receptor encephalitis is with plasmapheresis, immunosuppression and tumor removal when applicable. In our patient, the renal mass was localized and nephrectomy was curative. There are published cases of autoimmune encephalitis associated with lung and ovarian tumors, but no reported association with clear cell renal carcinoma exists, making this a rare case of anti-NMDA receptor encephalitis in a hospitalized patient.
Conclusions: Encephalopathy may present commonly in hospitalized patients, but uncommon causes should be considered when initial investigative data is ambiguous. In our case, the initial gram stain was a red herring, leading to a more extensive workup revealing anti-NMDA receptor encephalitis associated with clear cell renal cell carcinoma. Thankfully, the detailed workup allowed for timely curative treatment.