What are the timescales for the different phases of autoimmune encephalitis?

Timescales of the Different Phases of Autoimmune Encephalitis

Autoimmune encephalitis typically presents in distinct phases with specific timescales: the initial phase usually lasts days to weeks, followed by a second phase lasting weeks to months, with recovery taking months to years depending on antibody type and treatment timing. 1

Initial Presentation Phase

• Onset pattern: Acute to subacute presentation, typically developing over less than 3 months 1
• Prodromal period: Often preceded by viral-like prodrome, headache, and sometimes fever 1
• First phase duration:
  • For NMDAR encephalitis: First phase characterized by seizures, confusion, amnesia, and psychosis typically lasts days to a few weeks 1
  • For VGKC-complex antibody encephalitis: Faciobrachial dystonic seizures may precede the encephalitis by a few weeks 1

Second Phase/Progressive Phase

• NMDAR encephalitis: Second phase develops days to a few weeks after initial symptoms, characterized by involuntary movements (choreoathetosis, orofacial dyskinesia), fluctuations in consciousness, dysautonomia, and sometimes central hypoventilation 1
• Post-viral autoimmune encephalitis: When following HSV encephalitis, autoimmune encephalitis typically develops within 2 months (median 26-43 days depending on age) 2
  • In patients ≤4 years: Median interval of 26 days (IQR 24-32) between HSV encephalitis and autoimmune encephalitis 2
  • In patients >4 years: Median interval of 43 days (IQR 25-54) 2

Treatment Response Phase

• Initial response: Confusion and seizures typically improve rapidly with immunosuppression in most cases 1
• Antibody normalization: With high-dose oral steroids, antibody levels typically normalize within 3-6 months for VGKC-complex antibody encephalitis 1
• Steroid taper: Following antibody normalization, steroid dose is typically tapered over the next 12 months 1

Recovery Phase

• Memory improvement: Can take several months to years after initial presentation 1
• Hospital stay: For NMDAR encephalitis, median length of hospital stay is 160 days (range 16-850 days) with many requiring ICU admission for assisted ventilation 1
• Long-term recovery:
  • Most significant improvement occurs within 6-12 months after disease onset 3
  • Some patients with NMDAR encephalitis may continue to show substantial recovery even after 12 months of treatment 3

Disease Course Patterns

• VGKC-complex antibody encephalitis: Usually a monophasic illness; once antibodies become undetectable with treatment, they typically remain undetectable and relapse is uncommon 1
• NMDAR encephalitis: Can relapse in approximately 30% of cases, despite no evidence of tumor presence 1
• Chronic presentations: Only seen in some conditions, especially LGI1, CASPR2, DPPX, and GAD65-antibody encephalitis 1

Important Clinical Considerations

• Age significantly affects presentation and outcomes:

  • Younger patients (≤4 years) typically have shorter intervals between HSV encephalitis and autoimmune encephalitis onset, more choreoathetosis, decreased consciousness, and worse outcomes at 1 year 2
  • Older patients (>4 years) more commonly present with psychosis and have better responses to immunotherapy 2

• Early diagnosis and treatment are critical for improved outcomes:

  • Delays in escalating to second-line therapy are associated with poorer outcomes 4
  • Early initiation of rituximab in patients who fail first-line treatment can significantly improve neurological outcomes 4

Understanding these timescales is essential for prompt recognition, appropriate treatment timing, and setting realistic expectations for recovery in patients with autoimmune encephalitis.