IC‐P‐166: TAU PET IMAGING IN LGI1 ENCEPHALITIS: DECIPHERING THE CONTRIBUTORS TO COGNITIVE IMPAIRMENT IN AUTOIMMUNE ENCEPHALITIS

Autoimmune encephalitis associated with leucine-rich glioma-inactivated 1 (LGI1) antibodies is most common in older cohorts, may be mistaken for a neurodegenerative dementing illness at presentation, frequently results in persistent cognitive impairment in patients who recover, and is associated with changes on structural and functional neuroimaging in the bilateral hippocampi. The neuropathological underpinnings that contribute to long-term sequelae remain unknown. We investigated whether neurofibrillary tangle (tau) pathology contributed to persistent cognitive impairment in patients with LGI1 encephalitis. Flortaucipir (18F-AV-1451) “tau PET” neuroimaging was completed in four cognitively impaired LGI1 encephalitis patients (3 males, 1 female; median 67 years, range 37-88; median CDR 0.5, range 0.5-2), a median of 27.4 months (range, 4.2-54.6) following symptom onset. Regional SUVRs were derived using standard techniques with the cerebellar gray matter serving as a reference. Flortaucipir retention patterns were compared between LGI1 encephalitis patients and age-similar cognitively normal (CDR 0) amyloid negative participants (n=127) and amyloid positive individuals with symptomatic Alzheimer disease (AD, CDR>0; n=18) enrolled in longitudinal studies of memory and aging (Knight Alzheimer Disease Research Center; Saint Louis, Missouri). Flortaucipir retention was not increased in any brain region in 3/4 LGI1 encephalitis patients relative to cognitively normal individuals. In the remaining patient—an 88 year-old female with moderate dementia (CDR 2) persisting despite treatment with prednisone and rituximab—Flortaucipir retention was increased relative to cognitively normal controls in the lateral occipital, caudal middle frontal, temporal, fusiform, pericalcarine cortices, in a pattern indistinguishable from individuals with symptomatic AD. This patient died 2.4 months following tau-PET imaging. Neuropathological assessment confirmed “intermediate” AD neuropathologic change (NIA-AA criteria), with frequent neurofibrillary tangles in areas of greatest Flortaucipir uptake. The absence of substantial Flortaucipir retention in the majority of LGI1 encephalitis patients suggests that neurofibrillary tangles are unlikely to contribute to cognitive impairment in recovering patients. However, the possibility that autoimmune encephalitis may accelerate the accrual of tau pathology in individuals with preclinical AD, or other age-related pathologies associated with neurofibrillary tangles, warrants consideration in larger cohorts of patients followed longitudinally. Acknowledgements: Flortaucipir precursor and technology was supported by Avid Radiopharmaceuticals.