What are the typical MRI findings in autoimmune encephalitis, specifically in terms of Magnetic Resonance Imaging (MRI) sequences and brain regions affected?

MRI Findings in Autoimmune Encephalitis

Brain MRI with contrast is the primary imaging modality for autoimmune encephalitis, though approximately 39-61% of patients may have normal imaging at symptom onset, particularly in anti-NMDAR encephalitis. 1, 2

Key MRI Sequences and Protocol

• Standard brain MRI with and without contrast is the recommended imaging protocol for evaluating suspected autoimmune encephalitis 1, 3
• T2-weighted and FLAIR sequences are most sensitive for detecting hyperintensities in affected brain regions 4, 5
• Gradient echo sequences may help differentiate autoimmune encephalitis from herpes simplex encephalitis, though this distinction is not always reliable 1
• Diffusion-weighted imaging (DWI) can identify restricted diffusion in some cases, though susceptibility artifacts are rare (only 1.5% of cases) and their presence makes autoimmune encephalitis less likely 2

Anatomical Distribution Patterns

Limbic Encephalitis (Most Common Pattern)

• Bilateral medial temporal lobe T2/FLAIR hyperintensities are the hallmark finding, seen in approximately 33% of cases overall 2
• Bilateral limbic involvement is the only MRI pattern sufficient to diagnose definite autoimmune encephalitis in the appropriate clinical context (e.g., negative viral studies), even without positive antibodies 1
• Unilateral involvement occurs in only 18% of autoimmune encephalitis cases, whereas 96% of temporal lobe tumors present unilaterally 5
• Preservation of gray-white matter distinction at the cortical-subcortical interface is highly suggestive of autoimmune encephalitis (91% of cases) versus glioma (17% of cases) 5
• Hippocampal involvement can progress to atrophy over time, particularly in LGI1, CASPR2, GAD, and GABA-B receptor encephalitis 4

Other Anatomical Patterns

• Cortical/subcortical encephalitis: Multifocal, confluent T2/FLAIR hyperintense lesions in cortical and subcortical areas, particularly seen in GABA-A receptor encephalitis 4
• Striatal encephalitis: Involvement of basal ganglia structures 1
• Diencephalic encephalitis: Thalamic and hypothalamic involvement 1
• Brainstem encephalitis: More common in group 1 antibodies (intracellular antigens) 2
• Cerebellar involvement: Also more common in group 1 antibodies; can occur with GABA-B receptor encephalitis along with cerebellar atrophy 4, 2
• Encephalomyelitis: Combined brain and spinal cord involvement 1
• Meningoencephalitis: Brain parenchymal changes with meningeal involvement 1

Contrast Enhancement Patterns

• Diffuse or patchy enhancement suggestive of inflammation is seen in a minority of patients 1
• Intense enhancing lesions are unlikely in autoimmune encephalitis 1
• Leptomeningeal enhancement is more common in group 2 antibodies (extracellular/surface antigens) 2
• Radial perivascular enhancement is characteristic of autoimmune GFAP astrocytopathy 1
• Punctate brainstem/cerebellar enhancement suggests CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) 1

Antibody-Specific MRI Patterns

Anti-NMDAR Encephalitis

• Most patients (61% of those with normal MRIs) have unremarkable imaging in the acute stage 4, 2
• When present, lesions are typically subtle, non-specific white matter T2 hyperintensities that do not correlate with clinical severity 4
• White matter lesions may indicate overlap syndromes with MS, NMOSD, or MOGAD 4

LGI1, CASPR2, and GAD Antibody Encephalitis

• Unilateral or bilateral medial temporal lobe T2/FLAIR hyperintensities are typical 4
• Can progress to hippocampal atrophy over time 4

GABA-B Receptor Encephalitis

• Medial temporal hyperintensities similar to other limbic encephalitis patterns 4
• May additionally show cerebellar lesions and atrophy 4

GABA-A Receptor Encephalitis

• Multifocal, confluent lesions in cortical and subcortical areas 4
• Can lead to generalized atrophy 4

IgLON5 Disease

• MRI is unremarkable in most patients 4
• Individual cases may show T2/FLAIR hyperintensities, diffusion restriction, and atrophy in brainstem, hippocampus, and cerebellum 4

Critical Diagnostic Considerations

• A normal MRI does not exclude autoimmune encephalitis, particularly anti-NMDAR encephalitis where imaging is frequently normal 1, 4, 2
• Brain FDG-PET is more sensitive than MRI and should be obtained when MRI is negative but clinical suspicion remains high 1
• EEG should be performed if MRI is negative to confirm focal or multifocal brain abnormality 1
• The ALE-Plus pattern (bilateral medial temporal abnormalities plus extramedial temporal involvement) is more likely associated with antibody-negative cases (23.7%) than antibody-positive cases (2.3%) 6
• Parahippocampal gyrus T2/FLAIR hyperintensity is more suggestive of tumor (71%) than autoimmune encephalitis (18%) 5
• Mass effect and edema favor tumor over autoimmune encephalitis 5

Rare and Atypical Findings

• Focal or extensive demyelination can occur rarely 1
• Meningeal enhancement is an uncommon finding 1
• Hemorrhage/susceptibility artifacts are rare (1.5% of cases) and should prompt consideration of alternative diagnoses 2