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Anti-NMDA Receptor Encephalitis

Also Known As: Anti-N-methyl-D-aspartate receptor encephalitis, NMDA receptor antibody encephalitis, Autoimmune encephalitis (NMDA subtype)
System: Immune System and Nervous System
Autoantibodies: Anti-NMDA receptor antibodies (against the NR1 subunit of the NMDA receptor)
Primary Organ or Body Part Affected: Brain (particularly the limbic system and cortex)
Acceptance as Autoimmune: Confirmed
Anti-NMDA receptor encephalitis

What is Anti-NMDA Receptor Encephalitis?

Anti-NMDA receptor encephalitis is a serious autoimmune brain inflammation disorder. The immune system produces antibodies against NMDA receptors in the brain, which play a critical role in memory, behavior, and cognition. These antibodies disrupt normal brain signaling, leading to a wide range of psychiatric and neurological symptoms. It most often affects young women but can occur in anyone, including children and men.

What are the signs and symptoms of Anti-NMDA Receptor Encephalitis?

Symptoms often progress in phases, starting with psychiatric signs and moving to neurological and autonomic disturbances.

Early Symptoms (Psychiatric and Behavioral):

  • Anxiety, agitation, or paranoia

  • Hallucinations or delusions

  • Sudden personality changes

  • Insomnia

  • Confusion or memory problems

  • Catatonia

Neurological and Physical Symptoms:

  • Seizures

  • Abnormal movements (e.g., facial twitching, limb jerking, rigidity)

  • Difficulty speaking or mutism

  • Decreased consciousness or coma

  • Autonomic instability (e.g., erratic blood pressure or heart rate, fever, breathing issues)

What are the causes of Anti-NMDA Receptor Encephalitis?

  • Autoimmune reaction: The immune system produces antibodies targeting the NMDA (N-methyl-D-aspartate) receptors in the brain.

  • Triggering factors:

    • Tumors, particularly ovarian teratomas in women (most common trigger)

    • Viral infections (e.g., herpes simplex virus)

    • Idiopathic (no clear cause in some patients)

Diagnosis

  • Lumbar puncture (spinal tap): To detect antibodies in cerebrospinal fluid (CSF)

  • Blood tests: To identify anti-NMDA receptor antibodies

  • Brain MRI: May be normal or show signs of inflammation

  • Electroencephalogram (EEG): Often shows abnormal brain wave activity

  • Tumor screening: Especially in women, often includes pelvic ultrasound, CT, or MRI to look for ovarian teratomas

Treatment

First-line treatments:

  • High-dose corticosteroids

  • Intravenous immunoglobulin (IVIG)

  • Plasmapheresis (plasma exchange)

Second-line treatments (if first-line fails):

  • Rituximab (a B-cell depleting agent)

  • Cyclophosphamide (a chemotherapy drug with immunosuppressive effects)

Additional treatment:

  • Surgical removal of any tumor (especially ovarian teratoma)

  • Antipsychotic or seizure medications (cautiously used)

  • Intensive care for autonomic instability and seizures

  • Rehabilitation for cognitive and motor recovery

Prognosis

  • With prompt diagnosis and treatment, up to 80% of patients experience substantial recovery.

  • Recovery may take months or even years and often involves relapses or residual cognitive/psychiatric symptoms.

  • Without treatment, the condition can be life-threatening due to respiratory failure, autonomic dysfunction, or prolonged coma.

Prevalence

  • Estimated incidence: 1.5 per million people per year

  • More common in young women (especially ages 12–45), though it can affect all ages and sexes

  • Up to 50% of female cases are associated with ovarian teratomas

Citations

  • Dalmau, J., et al. (2007). Anti–NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. The Lancet Neurology, 7(12), 1091–1098.

  • Titulaer, M. J., et al. (2013). Treatment and prognostic factors for long-term outcome in patients with anti–NMDA receptor encephalitis: an observational cohort study. The Lancet Neurology, 12(2), 157–165.

  • Graus, F., & Dalmau, J. (2019). Autoimmune encephalitis: clinical clues and laboratory diagnosis. Nature Reviews Neurology, 15, 759–772.

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