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Observation
November 2015

Non–N-Methyl-D-Aspartate Receptor Antibody Encephalitis With Cerebellitis With Associated Ovarian Teratoma

Author Affiliations
  • 1Department of Neurology, University of Rochester Medical Center, Rochester, New York
JAMA Neurol. 2015;72(11):1375-1377. doi:10.1001/jamaneurol.2015.1531

The incidence of autoimmune and paraneoplastic encephalitis is increasing with improved recognition of clinical syndromes and diagnostic testing. Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis has been well described in young women with ovarian teratoma.1 The classic presentation of this syndrome is a subacute encephalopathy with mood disturbances, including psychosis, with variability of seizures and movement disorders. However, to our knowledge, there have been no reported associations between ovarian teratomas and paraneoplastic cerebellitis. Typically, paraneoplastic cerebellar degeneration or cerebellitis has been linked to anti-Yo antibody. More recently, cases of autoimmune and paraneoplastic cerebellitis have been reported with associated anti–Homer-3 and anti–metabotropic glutamate receptor 1 antibodies. Metabotropic glutamate receptor 1 has been associated with Hodgkin lymphoma, but there have been no reported neoplasms in cases of cerebellitis with positive Homer-3 antibodies.2,3

We present a case of meningoencephalitis with cerebellitis in a previously healthy woman with bilateral ovarian teratomas. Based on diagnostic evaluation and treatment response, we postulated a novel paraneoplastic cerebellitis with associated ovarian teratomas.

Report of a Case

A woman in her mid-20s with no medical history presented with 2 to 3 days of fever, headache, encephalopathy, and ataxia. Her examination was significant for fever, encephalopathy, dysarthria, hypophonia, ataxic speech, reduced visual acuity, truncal more than appendicular ataxia, and bilateral Babinski signs. Initial magnetic resonance imaging of the brain without and with contrast did not show any abnormality. Cerebrospinal fluid (CSF) was notable for elevated opening pressure of 30 cm H2O (184 nucleated cells; lymphocyte count of 86/µL [to convert to ×109 per liter, multiply by 0.001], elevated protein level of 137 mg/dL, and low glucose level at 36 mg/dL [to convert to millimoles per liter, multiply by 0.05555]). Given this CSF profile, she was initially treated empirically for infectious meningoencephalitis with broad-spectrum antibiotics, acyclovir and dexamethasone.

Over the course of the next week, she continued to have fevers; encephalopathy; autonomic instability, including central apnea and syndrome of inappropriate antidiuretic hormone secretion; and truncal and appendicular ataxia. All blood and CSF culture and polymerase chain reaction test results returned negative for an infectious etiology. Therefore, antimicrobial therapies were discontinued. A repeat magnetic resonance image of the brain again did not show any overt abnormality. Repeat CSF test results showed an opening pressure of 29.4 cm H2O, nucleated cell count of 396/µL, lymphocyte count of 89/µL, red blood cell count of 0/µL, glucose level of 46 mg/dL, and protein level of 99 mg/dL. A paraneoplastic panel of serum and CSF, including NMDAR antibody, was sent earlier in the course of her hospitalization and the test results were later found to be normal (Table). She started treatment with high-dose methylprednisolone for 5 days owing to concern for an autoimmune inflammatory condition. Immunotherapy with high-dose methylprednisolone and intravenous immunoglobulin resulted in rapid clinical improvement. A computed tomographic scan of her abdomen and pelvis showed a right adnexal mass suggestive of an ovarian teratoma (Figure). Pelvic ultrasonography confirmed bilateral ovarian teratomas. She subsequently underwent isolated teratomectomies without removal of either ovary. Teratomas were confirmed on pathological review. She was discharged to acute rehabilitation with a prednisone taper, with complete clinical resolution.

Table.  
Paraneoplastic Antibodies Tested During Hospitalizationa
Paraneoplastic Antibodies Tested During Hospitalizationa
Figure.
Computed Tomography of the Abdomen and Pelvis
Computed Tomography of the Abdomen and Pelvis

Coronal view of the abdomen and pelvis showing a right adnexal fat-containing mass with a soft tissue nodule in the wall (arrowhead).

Discussion

We describe a previously unrecognized, to our knowledge, neurologic complication of ovarian teratoma not associated with NMDAR antibodies but reversible with immunotherapy and tumor resection. We hypothesized that this disorder was mediated by non-NMDAR antibody autoimmunity triggered by ovarian teratoma. Similar cases have been reported with Homer-3 and metabotropic glutamate receptor 1 antibodies,2,3 but neither have been associated with ovarian teratomas. Further investigation for a novel antibody, including metabotropic glutamate receptor 1 and Homer-3, was not pursued in this case. Identification of novel antibodies and their associated clinical scenarios are critical to our understanding, recognition, and treatment of autoimmune (including paraneoplastic) encephalitides. Clinical suspicion for ovarian teratoma is warranted in young women presenting with noninfectious, nonlimbic encephalitic syndromes.

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Article Information

Corresponding Author: Andrew D. Smith III, MD, Department of Neurology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642 (andrewd_smith@urmc.rochester.edu).

Conflict of Interest Disclosures: None reported.

References
1.
Dalmau  J, Tüzün  E, Wu  HY,  et al.  Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007;61(1):25-36.
PubMedArticle
2.
Marignier  R, Chenevier  F, Rogemond  V,  et al.  Metabotropic glutamate receptor type 1 autoantibody-associated cerebellitis: a primary autoimmune disease? Arch Neurol. 2010;67(5):627-630.
PubMedArticle
3.
Höftberger  R, Sabater  L, Ortega  A, Dalmau  J, Graus  F.  Patient with homer-3 antibodies and cerebellitis. JAMA Neurol. 2013;70(4):506-509.
PubMedArticle
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