Rapid and accurate diagnosis of AE encourages prompt immunotherapy initiation, towards improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis. Further, awaiting autoantibody results can delay immunotherapy administration.

To identify simple MRI characteristics which accurately distinguish two common forms of autoimmune encephalitis (AE); LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from two major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD).

Retrospective, cross-sectional, blinded analysis of first available brain MRIs from 192 patients across two tertiary referral centres with LGI1/CASPR2-Ab-E, VE or CJD evaluated for predetermined MRI features by two neuroradiologists (discovery cohort; n=87) and validated in an independent cohort by three neurologists (n=105). Groups were statistically compared with contingency tables.

MRIs from 192 participants were reviewed (n = 71 female, 37%; median age = 66). By comparison to VE and CJD, in LGI1/CASPR2-Ab-E T2/FLAIR-hyperintensities were less likely to extend outside the temporal lobe (7% vs 94% in VE; P<0.001 and 75% in CJD; P<0.01), less frequently exhibited swelling (22% of LGI1/CASPR2-Ab-E vs 59% of VE; P<0.001), and showed no diffusion restriction (0%, vs 73% in VE and 80% in CJD; both P<0.001) and rare contrast-enhancement (5% vs 41% in VE, P=0.013). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90% and specificity 95% amongst cases with T2/FLAIRhyperintensity in the hippocampus and/or amygdala.

T2/FLAIR-hyperintensities confined to the temporal lobes, without diffusion restriction or contrast-enhancement, robustly distinguish LGI1/CASPR2-Ab-E from key differentials. These observations should assist clinical decision making towards expediting immunotherapy. Their generalisability to other forms of AE/VE should be examined in future studies.