What are the symptoms, duration, and clinical presentation of Anti-NMDA (N-methyl-D-aspartate) encephalitis?

Anti-NMDA Receptor Encephalitis: Symptoms, Duration, and Clinical Presentation

Anti-NMDA receptor encephalitis typically presents with a subacute onset of psychiatric symptoms, followed by neurological manifestations including dyskinetic movements, decreased consciousness, seizures, and autonomic instability, with recovery potentially taking months to years even with appropriate treatment.

Clinical Presentation and Symptom Progression

Anti-NMDA receptor encephalitis follows a characteristic pattern of symptom development:

Initial Phase (Psychiatric Manifestations)

• Behavioral disturbances - prominent psychiatric symptoms are typically the first manifestation 1
• New-onset psychosis - hallucinations, delusions, agitation 1
• Cognitive dysfunction - confusion, memory deficits 1
• Mood alterations - anxiety, depression, mania 2

Progressive Phase (Neurological Manifestations)

As the disease evolves, patients develop:

• Movement disorders:

  • Dyskinetic movements, particularly orofacial dyskinesias 1
  • Choreoathetosis (irregular, flowing movements) 1
  • Dystonia 2
  • Bucolingual dyskinesias (abnormal movements of mouth and tongue) 2

• Seizures - occur in approximately 85% of patients 1, 2

• Speech dysfunction - aphasia, mutism, loss of language 2

• Decreased consciousness - ranging from confusion to coma 1

• Autonomic instability - fluctuations in blood pressure, heart rate, temperature, and respiratory patterns 1

Demographic Patterns

• Age and gender distribution:
  • Originally described in young women with ovarian teratomas 1
  • Now recognized in both males and females of all ages 1
  • In pediatric populations, may occur without associated tumors 2
  • In patients under 30 years of age, anti-NMDAR encephalitis is the most common cause of encephalitis, exceeding the combined incidence of HSV, West Nile virus, and varicella zoster virus encephalitis 1

Disease Duration and Recovery

• Acute phase: Typically lasts weeks to months 3, 4
• Recovery phase:
  • Can be prolonged, with improvement occurring in the reverse order of symptom appearance 5
  • More than 75% of patients make substantial recovery 5
  • Recovery may be severely delayed in some cases, with significant improvement occurring as late as 30 months after symptom onset 3
  • Recovery is not always linear and can occur in stages 3

Diagnostic Considerations

• CSF findings:

  • CSF antibody testing is more sensitive than serum (approximately 15% higher sensitivity) 1
  • CSF may be normal in many pediatric patients 2
  • Oligoclonal bands may be present 2

• Neuroimaging:

  • Brain MRI is often normal 2
  • Functional studies like SPECT may show abnormalities even when MRI is normal 2

• EEG:

  • Abnormalities are common 2
  • Changes may persist even as clinical improvement occurs 4

Treatment Response and Prognosis

• First-line therapies:

  • Methylprednisolone
  • Intravenous immunoglobulin
  • Plasma exchange 5

• Second-line therapies (if first-line fails):

  • Rituximab
  • Cyclophosphamide 5

• Prognostic factors:

  • Early and aggressive immunosuppressive treatment appears to support better outcomes 4
  • Disease course often correlates with antibody titers 4
  • Tumor removal (if present) improves outcomes 5

Clinical Pitfalls and Caveats

• Anti-NMDAR encephalitis may be misdiagnosed as primary psychiatric disorder, delaying appropriate treatment 6
• HSV encephalitis can trigger subsequent development of anti-NMDAR antibodies, with approximately 24.5% of HSV encephalitis patients developing detectable CSF antibodies by 3 months 1
• Other viral infections including varicella zoster virus, Epstein-Barr virus, and influenza A virus have been associated with subsequent development of anti-NMDAR encephalitis 1
• Patients with viral encephalitis who exhibit slow response to antiviral therapy or develop recrudescent symptoms should be evaluated for autoimmune encephalitis 1
• Antibody levels may not always reliably correlate with disease activity 3