Focused deposition within limbic structures was seen in Case B, including the parahippocampal gyri (Z=2.61,P=0.009), amygdala (Z=2.17,P=0.03), and posterior cingulate cortices (Z=2.34,P=0.02). associate with cognitive complaints and hippocampal atrophy in recovering LGI1 patients. == Introduction == Autoimmune encephalitis associated with autoantibodies to the surfaceexposed leucinerich gliomainactivated 1 (LGI1) neuronal antigen most commonly affects individuals >60 years,1,2in whom it associates with persistent cognitive impairment and hippocampal atrophy.1,3,4,5It is unknown whether these changes result from classical immunemediated structural damage (i.e., neuronal loss secondary to complement or other immunemediated damage),6,7the accelerated accrual of neuropathology in susceptible individuals,8,9or other causes. The discovery of PET ligands capable of binding pairedhelical filaments that comprise neurofibrillary (tau) tangles provides a unique opportunity to evaluate the contribution of tau neuropathology to clinical phenotypes in living individuals. [18F]Flortaucipir (AV1451) exhibits reasonable specificity for tau neuropathology associated with Alzheimer disease (AD),10,11,12with tracer retention associated with clinical presentation,13,14disease severity and symptomatic decline.15,16,17We evaluated whether tau neuropathology measured with [18F]flortaucipir PET associated with persistent cognitive impairment and hippocampal atrophy in recovering LGI1 antibody encephalitis patients. One patient died 2.4 months following neuroimaging and underwent brainonly autopsy, providing a unique opportunity to correlate neuroimaging and neuropathological findings. == Methods == == Standard protocol approvals, registrations, and patient consents == Patients were enrolled from February 2016 to January 2017 within prospective studies permitting longitudinal collection and monitoring of clinical data and neuroimaging studies. Written informed consent UPGL00004 was obtained from all individuals or their delegates. The Washington University School of Medicine Institutional Review Board (Saint Louis, Missouri, USA) approved all study procedures. == Participant selection and evaluation == Patients with LGI1 antibody encephalitis were evaluated and treated by experienced clinicians at Barnes Jewish Hospital (Saint Louis, Missouri, USA). All patients met criteria for UPGL00004 definite autoimmune encephalitis.18LGI1 IgG autoantibodies were identified in the cerebrospinal fluid (CSF) or serum using cellbased assays (Mayo Clinic Neuroimmunology Laboratory; Rochester, Minnesota). Communitydwelling cognitively normal (CN) participants were enrolled in longitudinal studies of memory and aging at the Washington University Knight Alzheimer Disease Research Center (Saint Louis, Missouri). Cognitive impairment was graded using the Clinical Dementia Rating (CDR),19and quantified longitudinally using the 18point CDR sumofboxes.20,21CN participants were devoid of cognitive symptoms (CDR 0), and of substantial [18F]florbetapir (AV45) retention (i.e., amyloid negative; mean SUVR < 1.27). Participants with earlysymptomatic AD had typical (amnestic) presentations with very mild impairment (CDR 0.5) and increased [18F]florbetapir retention consistent with AD (mean SUVR 1.27).22AD cohort characteristics were previously reported.13 Structural MR (Biograph mMR) and [18F]flortaucipir PET neuroimaging (Biograph 40 PET/CT; Siemens Medical Solutions; Erlangern, Germany) were obtained in participants, as previously described.12,13[18F]Florbetapir PET images were obtained in CN participants and those with earlysymptomatic AD. Briefly, T1weighted images were acquired using magnetizationprepared rapidacquisition gradient echo sequences, before cortical and subcortical parcellation was performed using FreeSurfer 5.3 (http://freesurfer.net), yielding UPGL00004 46 unique brain regions, corresponding to the Desikan atlas. Imaging was performed following injection of 6.810.9 mCi of flortaucipir or 7.411.3 mCi of florbetapir. Data from the 80 to 100min and 50 to 70min postinjection window were converted to SUVRs, respectively, using the cerebellar cortex as a UPGL00004 reference; regional values were partial volume corrected using a geometric transfer matrix approach.23,24For visualization only, voxelwise PET were aligned to an individual patients T1 Rabbit polyclonal to HPSE image and placed into a common anatomic space. [18F]flortaucipir retention was summarized using the average SUVR across all cortical regions and areas commonly affected in AD, including the left and right inferior temporal cortex, amygdala, entorhinal cortex, and lateral occipital cortices.25 Brainonly autopsy was performed in one patient who died following enrollment. Microscopic analyses included immunohistochemical staining with antiA (142, clone H31L21) and antiphosphorylated tau (clone AT8) antibodies, performed by the Anatomic and Molecular Pathology Core Laboratory (Washington University School of Medicine), using a polymerbased detection system and instrumentation by Ventana Medical Systems. == Statistical analyses == Clinical data were analyzed using SPSS Statistics (version 25.0; IBM Corp., Armonk, NY). On a regionbyregion basis individuals SUVR values were transformed into zscores relative to the mean and standard deviation of a cohort of 124 CN participants.Pvalues for thezscores were inferred from the standard normal distribution. Correlations between neuroimaging findings and outcomes.