An Atypical Neuropsychiatric Condition: Anti-NMDA Receptor Encephalitis 3/19/2020

Although not a bread and butter primary care concern, Anti-NMDA Receptor Encephalitis is a recently recognized autoimmune process that can cause significant psychiatric, neurological and medical sequelae and it is an organic systemic disorder that may first present in the primary care setting. (NMDA = N-Methyl-D-Aspartate.) In the last decade, it has been more widely recognized in the pediatric population, and the importance of early detection and treatment has become established.

The pathophysiology of the condition arises from auto-antibodies that attack components of the NMDA receptors. These receptors are active in the glutamate pathways in the brain, concentrated in the forebrain, pituitary, hypothalamus and the limbic system. The activity appears to lead to decreased activity of these pathways, resulting neurological and psychiatric symptoms. The cause of the autoimmune reaction is not always clear. Often in adults, the condition can be para-neoplastic in nature, associated with ovarian tumors, but this is less so for adolescents. According to UpToDate, 50% of cases in adult women are associated with ovarian teratoma, while less than 9% of girls younger than 14 with the diagnosis will have a tumor.

Presentation can be quite variable but typically includes a prodromal period in which symptoms are generalized and flu-like, followed by progressively more complex psychiatric and neurological symptoms. Often, psychiatric manifestations are first to follow the prodromal period, and can include psychotic, depressive, anxious states and catatonic states. Neurological symptoms may include seizures, de novo cognitive deficits, abnormal movements and language dysfunction. In severe cases, autonomic instability can ensue and be life threatening. The time course of the progression is variable, but the initiation of supportive and targeted treatments prevents morbidity and reduces mortality rates.

The diagnostic workup is broad, and if the condition is suspected, would include a spinal tap with specific panels for ANTI-NMDA and other cerebral antibodies, an EEG, and an MRI. The diagnosis is confirmed with presence of NDMA specific IgG in the CSF. An investigation for possible tumors is also indicated.

Treatment includes tumor resection for tumor positive cases. First line systemic treatments include IV steroids, IV IG, or Plasma exchange. Second line treatment includes rituximab and/ or cyclophosphamide. Psychiatric medications, including benzodiazepines for catatonias, and anti-psychotics for psychotic symptoms are often required. Patients are often continued on psychiatric medications and require close follow-up with psychiatry and neurology for months or years following the diagnosis.

In the primary care setting, it may be helpful to pay attention to red flags, such as abrupt onset of psychiatric symptoms that were not previously present; the combination of emotional disturbances or bizarre behaviors with any kind with new-onset abnormal movements, seizures or abnormal levels of consciousness. It can be helpful to seek out psychiatric and neurological consultation for suspected cases. Since time is of the essence, accessing a consultation services with a quick turn-around time, such as Smart Care may be of benefit in decision making and arranging for a prompt psychiatric consultation.

Scheer, S., & John, R. M. (2016). Anti–N-Methyl-D-Aspartate Receptor Encephalitis in Children and Adolescents. Journal of Pediatric Health Care, 30(4), 347–358.

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