Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis

Abstract

Autoimmune encephalitis is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with refractory seizure. Due to its diverse clinical features, which can mimic a variety of other pathologic processes, autoimmune encephalitis presents a diagnostic challenge to clinicians. Imaging findings in patients with these disorders can also be quite variable, but recognizing characteristic findings within limbic structures suggestive of autoimmune encephalitis can be a key step in alerting clinicians to the potential diagnosis and ensuring a prompt and appropriate clinical work-up. In this article, we review antibody-mediated encephalitis and its various subtypes with a specific emphasis on the role of neuroimaging in the diagnostic work-up.

Fig 1.

Anti-Hu encephalitis. A 68-year-old man with chronic obstructive pulmonary disease presented with gradually worsening memory deficits and confusion, with subclinical seizures. MR imaging of the brain demonstrates T2-FLAIR hyperintensity and mild expansion in the right medial temporal lobe (A), right insular cortex (not shown), and left dorsal thalamus (not shown), without restricted diffusion (not shown) or postcontrast enhancement (not shown). FDG-PET of the brain demonstrates a hypermetabolic focus within the right medial temporal lobe lesion (B). PET of the body demonstrates a hypermetabolic focus in the left lung (E), consistent with biopsy-proved small-cell lung cancer. The patient was in remission following treatment with intravenous immunoglobulin infusions, oral steroids, and chemotherapy, but he presented approximately 2.5 years later with worsening memory decline. MR imaging at that time (C and D) shows new T2-FLAIR hyperintensity in the left medial temporal lobe (white arrow) with volume loss within the right medial temporal lobe (white arrowhead). An old right occipital lobe infarct is also incidentally noted.

Fig 2.

Graves ophthalmopathy with anti-Hu encephalitis. A 63-year-old woman with severe encephalopathy and diffuse enlargement of the extraocular muscles developed fatal autonomic dysfunction. MR imaging of the brain demonstrates prominent T2-FLAIR abnormalities in the mesial temporal lobes (A), right thalamus (B), right > left insular cortex (B), and posterior right temporal lobe (B), without enhancement (C) and with T2 shinethrough but no restricted diffusion on DWI (D) and the corresponding ADC map (E). There is also diffuse symmetric enlargement of the extraocular muscles, resulting in exophthalmos (F).

Fig 3.

Anti-glutamic acid decarboxylase encephalitis. A 61-year-old woman presented with headaches, mild confusion, and nystagmus without development of psychosis, severe encephalopathy, or seizures. MR imaging of the brain demonstrates T2-FLAIR hyperintensity in the right > left hippocampus (A and B), right > left insular cortex (B), and bilateral cingulate gyrus (C and D) without restricted diffusion (not shown), hemorrhage (not shown), or postcontrast enhancement (not shown).

Fig 4.

Anti-N-methyl D-aspartate receptor encephalitis. A 32-year-old woman presented with headaches, vertigo, and psychosis with subsequent development of encephalopathy and seizures. MR imaging of the brain performed after the onset of seizures 2 weeks after initial presentation demonstrates T2-FLAIR hyperintensity in the left inferior temporal lobe (A), left > right insular cortex (B and C), and left > right cingulate gyrus (B–D), without restricted diffusion (not shown), hemorrhage (not shown), or postcontrast enhancement (not shown).

Fig 5.

Anti-voltage-gated calcium channel encephalitis. A 39-year-old woman presented with left-sided weakness and left visual field deficits with subsequent development of encephalopathy and seizures. Initial MR imaging of the brain (A–D) demonstrates multifocal T2-FLAIR hyperintense lesions in the right parieto-occipital region (A), with associated pial/sulcal enhancement (B) and mild cortical restricted diffusion and T2 shinethrough within the subcortical white matter on DWI (C) and the corresponding ADC map (D). Follow-up MR imaging of the brain performed 34 days later (E–H) demonstrates decreased T2-FLAIR hyperintensity (E) with cortical laminar necrosis and petechial hemorrhage (F) at the original lesion, with progressive development on subsequent examinations of similar cortical lesions in the contralateral frontal, parietal, and occipital lobes (E–H).

Fig 6.

Anti-voltage-gated calcium channel cerebellitis. A 23-year-old woman with a history of autoimmune hepatitis presented with altered mental status. Initial brain MR imaging (A–E) demonstrates T2-FLAIR hyperintensity within the bilateral cerebellar hemispheres with mass effect on the fourth ventricle (A and B), without evidence of postcontrast enhancement (C) and with mild restricted diffusion on DWI (D) and the corresponding ADC map (E). A follow-up scan 1 month later (F) demonstrates resolution of the T2-FLAIR hyperintensity and associated mass effect on the fourth ventricle following a steroid taper.

Fig 7.

Hashimoto encephalitis. A 41-year-old woman presented with gradually worsening headaches and memory impairment without the development of psychosis or seizures. MR imaging of the brain (time, 0) demonstrates T2-FLAIR hyperintensity in the inferior left temporal lobe (A) without evidence of restricted diffusion (B and C). MR imaging of the brain (time, 21 days) demonstrates enlargement of the lesion on T2-FLAIR (not shown) without postcontrast enhancement (D). MR imaging of the brain (time, 3 months) demonstrates resolution of the prior lesion (not shown) but development of similar T2-FLAIR hyperintensity in the right frontoparietal junction (E). A subsequent scan at approximately 5 months shows near-complete resolution of that lesion with a new T2-FLAIR hyperintense lesion more posteriorly (F). A follow-up scan (G and H) nearly 1 year from onset shows complete resolution of the imaging abnormalities.