Cortical and Subcortical Dysmetabolism Are Dynamic Markers of Clinical Disability and Course in Anti-LGI1 Encephalitis

Eero Rissanen, Kelsey Carter, Steven Cicero, John Ficke, Marie Kijewski, Mi Ae Park, Joseph Kijewski, Emily Stern, Tanuja Chitnis, David Silbersweig, Howard L. Weiner, Chun K. Kim, Jennifer Lyons, Joshua P. Klein, Shamik Bhattacharyya, Tarun Singhal

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Background and Objective s : 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.

Original languageEnglish
Article numbere1163
JournalNeurology: Neuroimmunology and NeuroInflammation
Issue number2
StatePublished - 25 Mar 2022
Externally publishedYes


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