What are the clinical features of autoimmune encephalitis?

Clinical Features of Autoimmune Encephalitis

Autoimmune encephalitis (AE) typically presents with a polysyndromic clinical picture characterized by multifocal brain inflammation, resulting in a combination of cognitive, psychiatric, and neurological manifestations that develop subacutely over days to weeks. 1

Core Clinical Manifestations

Neuropsychiatric Symptoms

• Cognitive dysfunction

  • Disorientation (76% of cases)
  • Memory deficits, particularly short-term memory
  • Confusion and altered mental status
  • Speech disturbances (59% of cases)

• Behavioral and psychiatric changes (41% of cases)

  • Personality changes
  • Psychosis
  • Agitation
  • Hallucinations
  • Irritability
  • Insomnia
  • Depression or mania
  • Can be mistaken for primary psychiatric disorders 1, 2

Neurological Symptoms

• Seizures (approximately one-third of patients)

  • New-onset seizures
  • Refractory status epilepticus
  • Faciobrachial dystonic seizures (particularly in LGI1-antibody encephalitis)

• Movement disorders

  • Oromandibular dyskinesia (particularly in NMDAR-antibody encephalitis)
  • Choreoathetosis
  • Dystonia
  • Other abnormal movements

• Speech disturbances

  • Dysphasia
  • Aphasia
  • Mutism

• Autonomic instability

  • Blood pressure fluctuations
  • Cardiac arrhythmias
  • Hyperthermia
  • Hypoventilation (may require mechanical ventilation)

Other Features

• Fever (common but may be low-grade)
• Headache
• Nausea and vomiting
• Hyponatremia (particularly in LGI1-antibody encephalitis)

Antibody-Specific Clinical Features

While there is significant symptom overlap between different antibody types, certain features are more characteristic of specific antibodies:

NMDAR-Antibody Encephalitis

• Oromandibular dyskinesia
• Cognitive and behavioral changes
• Speech dysfunction
• Autonomic instability
• Bilateral occipito-parietal hypometabolism on FDG-PET

LGI1-Antibody Encephalitis

• Faciobrachial dystonic seizures (FBDS)
• Hyponatremia
• Frequent subclinical seizures
• Bilateral temporal hypermetabolism on FDG-PET

Clinical Course and Progression

The disease typically follows a characteristic progression:

1. Prodromal phase

   • Viral-like symptoms (fever, headache)
   • May follow viral infection, particularly HSV encephalitis 1

2. Early phase

   • Psychiatric symptoms often predominate
   • Behavioral changes
   • Cognitive decline

3. Advanced phase

   • Seizures
   • Movement disorders
   • Autonomic instability
   • Decreased consciousness

Risk Factors and Associations

• Paraneoplastic triggers: Patients with risk factors for malignancy (smoking, age >50, unintentional weight loss) are prone to paraneoplastic AE 1
• Autoimmune predisposition: Personal or family history of autoimmune disorders increases risk of idiopathic AE 1
• Iatrogenic triggers: Immune checkpoint inhibitors, TNFα inhibitors 1
• Post-infectious: May follow HSV encephalitis 1

Diagnostic Pitfalls

• Misdiagnosis as primary psychiatric disorder due to predominant psychiatric symptoms 2, 3
• Confusion with drug or alcohol intoxication 1
• Delayed diagnosis due to subtle initial presentation 1
• Negative antibody testing does not rule out AE (seronegative AE) 4

Anatomical Classification

The clinical presentation varies according to the anatomical localization of inflammation:

1. Limbic encephalitis

   • Memory deficits
   • Behavioral changes
   • Seizures

2. Cortical/subcortical encephalitis

   • Cognitive dysfunction
   • Seizures
   • Focal neurological deficits

3. Striatal encephalitis

   • Movement disorders
   • Behavioral changes

4. Brainstem encephalitis

   • Autonomic dysfunction
   • Cranial nerve abnormalities
   • Altered consciousness

5. Combined syndromes

   • Multiple anatomical regions affected
   • Polysyndromic presentation

Clinical Red Flags for AE

• Subacute onset (days to weeks) of neuropsychiatric symptoms
• Combination of cognitive, psychiatric, and neurological features
• New-onset seizures, particularly if refractory to treatment
• Movement disorders, especially orofacial dyskinesias
• Autonomic instability
• Hyponatremia without other explanation
• Lack of response to antipsychotics for psychiatric symptoms
• History of recent viral illness or cancer

Early recognition of these clinical features is crucial, as outcomes depend on prompt initiation of immunotherapy. When AE is suspected based on clinical features, appropriate investigations (MRI, EEG, CSF analysis) should be performed without delay, and empiric immunotherapy should be considered even before antibody results are available 5.