PT - JOURNAL ARTICLE AU - Rissanen, Eero AU - Carter, Kelsey AU - Cicero, Steven AU - Ficke, John AU - Kijewski, Marie AU - Park, Mi-Ae AU - Kijewski, Joseph AU - Stern, Emily AU - Chitnis, Tanuja AU - Silbersweig, David AU - Weiner, Howard L. AU - Kim, Chun K. AU - Lyons, Jennifer AU - Klein, Joshua P. AU - Bhattacharyya, Shamik AU - Singhal, Tarun TI - Cortical and Subcortical Dysmetabolism Are Dynamic Markers of Clinical Disability and Course in Anti-LGI1 Encephalitis AID - 10.1212/NXI.0000000000001136 DP - 2022 Mar 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e1136 VI - 9 IP - 2 4099 - http://nn.neurology.org/content/9/2/e1136.short 4100 - http://nn.neurology.org/content/9/2/e1136.full SO - Neurol Neuroimmunol Neuroinflamm2022 Mar 01; 9 AB - Background and Objectives This [18F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti–leucine-rich, glioma–inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined.Methods FDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non–LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses.Results P-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non–LGI1-AE group, AD group, and NCs (all p < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84–0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non–LGI1-AE groups when compared with NCs (both p < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all p < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up.Discussion Semiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE.Classification of Evidence This study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.[18F]FDG=[18F]fluorodeoxyglucose; AAL=automated anatomical labeling; AD=Alzheimer disease; AE=autoimmune encephalitis; AMPA=α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; APS=antiphospholipid syndrome; AUC=area under the curve; BWH=Brigham and Women's Hospital; DMN=default mode network; FBDS=facio-brachial dystonic seizures; GABA=gamma-aminobutyric acid; HE=Hashimoto encephalopathy; IQR=interquartile range; LE=limbic encephalitis; LGI1=leucine-rich, glioma–inactivated-1; mRS=modified Rankin scale; MTL=mediotemporal lobe; NC=negative controls; P/Mi=putamen-to-midbrain ratio; P/Th=putamen-to-thalamus ratio; P-SUVRg=putaminal global brain normalized SUV ratio; ROC=receiver operating characteristic; ROI=regions of interest; SS=Sjögren syndrome; SUVR=standardized uptake value ratio