A Patient With Encephalitis Associated With NMDA Receptor Antibodies

Discussion of Diagnosis

The syndrome of this patient along with the MRI findings, CSF inflammatory features, and history of an ‘ovarian cyst’ raised suspicions of the presence of a type of paraneoplastic encephalitis that has recently been described in patients with teratoma.[1] The disorder associates with antibodies to NMDAR and affects young women, who are then often hospitalized for psychiatric care with diagnoses of acute schizophrenia, catatonia, drug abuse, or malingering.[2] It is not until the patient develops seizures, autonomic instability, dyskinesias or a decreased level of consciousness that an organic illness is considered. Less frequently, patients present with severe short-term memory deficits resembling limbic encephalopathy.[3]

Box 1 outlines the clinical features of this type of paraneoplastic encephalitis, which often evolves as follows: psychiatric or ‘limbic’ presentation with seizures, decline of consciousness, dysautonomia and movement disorder, and recovery after treatment.[2,4,5] At times patients might remain with eyes open, mumbling or unresponsive, with increased muscle tone, similar to catatonia. In 25% of patients, FLAIR or T2 abnormalities in medial temporal or frontobasal regions are observed, sometimes with mild or transient meningeal enhancement as occurred in the present case.[2]

NMDAR antibodies are present in serum and CSF, usually with intrathecal synthesis, and are sometimes only detected in the CSF. The main target epitopes are in the NR1/NR2 heteromers of the NMDAR. The major antigen is NR1/NR2B, which is predominantly expressed in the hippocampus and forebrain, but reactivity with other NR1/NR2 heteromers is frequently observed.[2] In the present case, the patient had serum and CSF antibodies that reacted with all NR1/NR2 heteromers (NR2A-NR2D).

The associated tumors are mature (dermoid cyst) or immature teratomas of the ovary; recurrent or bilateral tumors can occur.[6] A CT scan and ultrasound of the pelvis, or intravaginal ultrasound, usually reveals the tumor. As 70% of the tumors are benign, PET scans can be negative.[1] In one patient the teratoma was in the mediastinum.[2] In all patients studied the NMDAR antibodies reacted with nervous tissue contained in the tumor (J Dalmau, unpublished data).[2]