NMDA-Receptor Antibody by CBA, Spinal Fluid
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Patients with NMDA-receptor antibody (targeting the GluN1 [NR1] subunit of this ionotropic glutamate receptor) have a fairly stereotyped neurological disorder, as described by Dalmau and colleagues. This disorder often develops in several stages. Prodromal symptoms include headache, fever, nausea, vomiting, diarrhea, or upper respiratory tract symptoms. Shortly afterwards, patients develop psychiatric symptoms and many initially come to the attention of psychiatrists. Anxiety, insomnia, fear, delusions, mania, and paranoia frequently occur; drug-induced psychosis may be suspected. Other behavioral changes include social withdrawal and stereotyped behavior. Amnesia and an unusual language disorder (noncortical aphasia) are common. The behavioral changes in children may be less specific and include temper tantrums and hyperactivity. Neurological disorders including seizures and dystonia are frequent, and may be the presenting symptom. After these initial symptoms, in both adults and children, decreased responsiveness ensues. Movement disorders include oro-lingual-facial dyskinesias, generalized chorea, oculogyric crisis, dystonia, and rigidity. Autonomic manifestations include hyperthermia, tachycardia, hypersalivation, hypertension, bradycardia, hypotension, urinary incontinence, and erectile dysfunction. Hypoventilation may necessitate extended ventilatory support (often months). Dissociative responses similar to those caused by NMDA-receptor antagonists (eg, phencyclidine or ketamine) have been observed (eg, resisting eye opening despite lack of response to painful stimuli).
The female:male ratio of patients is about 8:1. Overall, ovarian teratoma is encountered in approximately 50% of affected women. The most useful screening tests include magnetic resonance imaging (MRI) of pelvis, computed tomography (CT) scan, and pelvic and transvaginal ultrasound. The detection of teratoma is dependent on age and ethnic background; the younger the patient, the less likely that teratoma will be detected; black women are more likely to have teratoma than other ethnic groups. Only 2% have a neoplasm other than ovarian teratoma. Neoplasms documented in women include breast adenocarcinoma, ovarian neuroendocrine tumors, sex cord stromal tumor, pseudopapillary neoplasm of pancreas, neuroblastoma, and Hodgkin lymphoma. Neoplasia has been documented in 5% of men: testicular germ cell tumors or small-cell lung carcinoma.
Simultaneous testing of serum and cerebrospinal fluid (CSF) is recommended, because CSF is often more informative for NMDA-receptor antibody.
Evaluating new onset encephalopathy (noninfectious or metabolic) comprising 1 or more of the following: confusional states, psychosis, delirium, memory loss, hallucinations, movement disorders, seizures, or hypoventilation
Evaluating limbic encephalitis
Directing a focused search for cancer
Investigating encephalopathy appearing in the course or wake of cancer therapy, and not explainable by metastasis or drug effect
This is a valuable serological marker of autoimmune encephalopathy and of a patient's immune response to cancer (usually teratoma). NMDA-receptor autoantibodies are usually accompanied by subacute neurological symptoms and signs, and not found in healthy subjects.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A negative result does not exclude autoimmune encephalopathy or cancer.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Dalmau J, Lancaster E, Martinez-Hernandez E, et al: Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10:63-74