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

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

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

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 microhaemorrhages 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

Case 1

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.

Differential diagnosis	Differentiating feature
Viral encephalitis (HSV)	Asymmetric medial temporal/insular FLAIR and DWI hyperintensity with haemorrhagic change
Primary CNS lymphoma	MRI shows enhancing mass lesions; CSF cytology/flow cytometry positive for malignant cells
Creutzfeldt-Jakob disease	Cortical ribbon and basal ganglia DWI restriction; pulvinar/hockey-stick sign
CNS vasculitis	Vessel wall enhancement on MRI; infarcts; microhaemorrhages, angiography shows beading/stenosis of vessels
Glioma (temporal lobe)	Mass effect; irregular enhancement; does not resolve on follow-up
Mitochondrial encephalopathy (MELAS)	Stroke-like cortical lesions not respecting vascular territories; lactate peak on MRS