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Autoimmune Encephalitis

Summary

  • Autoimmune encephalitis encompasses a group of inflammatory brain disorders caused by antibodies targeting neuronal cell surface or synaptic proteins
  • Presents with subacute onset of memory deficits, altered mental status, psychiatric symptoms, and seizures
  • MRI typically shows T2/FLAIR hyperintensity in medial temporal lobes, though can be normal in up to 50% of cases

Pathophysiology

  • Antibody-mediated mechanisms
    • Cell surface/synaptic protein antibodies (e.g., NMDAR, LGI1, CASPR2, AMPAR, GABA-B receptor)
    • Intracellular antibodies (e.g., anti-Hu, anti-Ma2, anti-GAD65)
  • Pathogenic processes
    • Receptor internalization and decreased synaptic density
    • Direct blockade of receptor function
    • Complement activation and neuronal damage
  • Associated triggers
    • Paraneoplastic (ovarian teratoma with anti-NMDAR, small cell lung cancer with anti-Hu)
    • Post-infectious (HSV encephalitis preceding anti-NMDAR encephalitis)
    • Idiopathic

Demographics

  • Age distribution
    • Anti-NMDAR: predominantly young adults and children (median age 20-25 years)
    • Anti-LGI1: older adults (median age 60-65 years)
    • Anti-CASPR2: middle-aged to older men
  • Gender predilection
    • Anti-NMDAR: female predominance (4:1), especially with ovarian teratoma
    • Anti-LGI1 and CASPR2: male predominance (2:1)
  • Incidence
    • Estimated 0.8-1.2 per 100,000 person-years
    • Anti-NMDAR is most common, accounting for ~80% of cases

Diagnosis

  • Clinical presentation
    • Prodromal phase: headache, fever, flu-like symptoms
    • Psychiatric symptoms: psychosis, agitation, catatonia, hallucinations
    • Memory deficits and cognitive dysfunction
    • Seizures (focal or generalized)
    • Movement disorders: orofacial dyskinesias, choreoathetosis, dystonia
    • Autonomic dysfunction: cardiac arrhythmias, hyperthermia, hypoventilation
  • Laboratory findings
    • CSF: lymphocytic pleocytosis, elevated protein, oligoclonal bands
    • Antibody testing: serum and CSF (CSF more sensitive)
    • EEG: extreme delta brush pattern (anti-NMDAR), focal temporal abnormalities
  • Diagnostic criteria
    • Probable: compatible clinical syndrome with CSF pleocytosis or EEG/MRI abnormalities
    • Definite: antibody positive with compatible clinical syndrome

Imaging

  • MRI findings
    • T2/FLAIR: hyperintense signal in medial temporal lobes (hippocampi, amygdala)
    • T2/FLAIR: cortical/subcortical hyperintensities in other regions (frontal, parietal, insular)
    • T2/FLAIR: basal ganglia hyperintensity (particularly in anti-NMDAR)
    • T1: typically isointense to hypointense in affected regions
    • T1+C: variable enhancement (mild leptomeningeal or parenchymal)
    • DWI: restricted diffusion uncommon, may occur in severe cases
    • SWI: usually normal, occasional microhemorrhages in severe cases
  • Pattern by antibody type
    • Anti-NMDAR: normal MRI in 50-60%, or T2 hyperintensity in hippocampi, cortex, subcortical regions
    • Anti-LGI1: unilateral or bilateral medial temporal T2/FLAIR hyperintensity
    • Anti-CASPR2: medial temporal and basal ganglia T2 hyperintensity
    • Anti-GABA-B: bilateral medial temporal T2 hyperintensity with restricted diffusion
  • **FDG-PET findings

Differential diagnosis

Differential diagnosis Differentiating feature
Viral encephalitis CSF shows pleocytosis with positive viral PCR; acute onset with fever and systemic symptoms
Primary CNS lymphoma MRI shows enhancing mass lesions; CSF cytology/flow cytometry positive for malignant cells
Creutzfeldt-Jakob disease EEG shows periodic sharp wave complexes; positive RT-QuIC or 14-3-3 protein in CSF
Toxic-metabolic encephalopathy Improves with correction of underlying metabolic disturbance; no CSF pleocytosis
Psychiatric disorders Normal CSF, EEG, and MRI; absence of focal neurological signs
CNS vasculitis Vessel wall enhancement on MRI; angiography shows beading/stenosis of vessels
Neurosarcoidosis Elevated ACE levels; hilar lymphadenopathy on chest imaging; leptomeningeal enhancement
Wernicke encephalopathy Low thiamine levels; characteristic MRI changes in mammillary bodies and periaqueductal gray
Seizure disorder/status epilepticus EEG shows epileptiform activity; responds to antiepileptic drugs without immunotherapy
Glioma MRI shows space-occupying lesion with mass effect; absence of antibodies
Hashimoto encephalopathy Elevated anti-thyroid antibodies; typically steroid-responsive without other immunotherapy
Mitochondrial encephalopathy Elevated lactate in CSF/serum; stroke-like lesions not respecting vascular territories on MRI

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  • A 20-year-old patient presented with confusion, headache and low grade fever.
  • MRI showed swelling and FLAIR and DWI hyperintensity affecting the hippocampi (L>>R).
  • GABA-B antibodies were identified within CSF.
  • 1 year later, the hyperintensity persisted within atrophic hippocampi.