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The diagnosis of the paraneoplastic syndrome called anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is based upon the clinical history and examination, followed by the demonstration of antibodies to the NMDAR, 7 proscar finasteride either the NR1 or NR2 (also called the Gln1) subunits.

It is known that the highest sensitivity and specificity occur using combined techniques for cerebrospinal fluid (CSF) testing, such as brain immunohistochemistry and CBA using fixed cells in preference to serum testing.

Treatment Principles

First Line Treatment

Treatment of anti-NMDAR encephalitis is mostly initiated with first-line immunotherapy modalities such as:

• Corticosteroids
• Intravenous immunoglobulin (IVIG) – to reduce the level of synthesis of endogenous anti-NMDAR antibodies and arrest further neuronal damage
• Plasmapheresis or plasma exchange – to reduce the antibody titer

Tumor removal should be done whenever a tumor is identified, and surgery is feasible. It may also be attempted in scan-negative cases with refractory symptoms, as occult teratomas have been found to be present following the histologic examination of such an ovary, with improvement of clinical features after the surgery.

Second-Line Treatment

In case of failure of this first-line therapy, second-line treatment consists of:

• Rituximab
• Cyclophosphamide

It was observed in one large study involving multiple institutions that 94% of patients had either removal of the tumor or first-line immunotherapy. The first line of treatment usually included steroids with IVIG, in 44%. Within a month of initiation, there was a significant improvement in 53%.

Of the 47% who failed to improve with first-line treatment, 57% were put on second-line immunotherapy and showed improvement over those who were not, or who stopped immunotherapy. The overall improvement was about 79% at 24 months. The risk of relapse was 12% in this period, but in 67% of patients the relapses were more tolerable than the initial presentation. The condition improves with more careful follow-up, until about 18 months after onset, at which time no more increase in recovery statistics is seen. The mortality at 24 months is about 10%.

It is noteworthy that starting the treatment with second-line immunotherapy reduced the frequency of relapses, and similarly, the use of second-line immunotherapy reduced the incidence of relapses in those patients in whom no tumor was present. When a relapse was treated with second-line drugs, there were fewer relapses in the following years. In addition, the occurrence of a relapse should prompt the search for or treatment of for an unidentified or untreated tumor, especially a teratoma, or consideration of the possibility of tumor recurrence.

Psychiatric disturbances are usually managed using antipsychotic drugs, both typical and atypical. Haloperidol, even at low doses, is often associated with extrapyramidal symptoms in such patients, and this may be mistaken for neuroleptic malignant syndrome. Corticosteroid administration may induce psychosis, while clonidine and benzodiazepines are successful in inducing sleep. Catatonic symptoms may be treated with lorazepam.

Prognostic Factors

The primary determinants of a poor outcome, including death, or of relapse include:

• High or increasing titers of antibodies in serum and CSF
• Failure of CSF antibody titers to decrease within four weeks of onset of the syndrome
• Late initiation of treatment (after 3 months of the onset of symptoms)
• Severe initial presentation
• A GCS (Glasgow Coma Scale) of 8 or less at admission which shows the depth of unconsciousness and hence the severity of antibody attack on the brain neurons
• Number of complications
• Admission to the intensive care unit

Further Reading

• All Encephalitis Content
• What is Encephalitis?
• What can Aedes mosquitos transmit?
• Autoimmune Encephalitis Classification
• Autoimmune encephalitis

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.