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

doi:10.1212/NXI.0000000000001136

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

Neurol Neuroimmunol Neuroinflamm. 2022 Jan 28;9(2):e1136. doi: 10.1212/NXI.0000000000001136. Print 2022 Mar.

Authors

Affiliations

¹ From the PET Imaging Program in Neurologic Diseases (E.R., K.C., S.C., J.F., T.S.) and Brigham Multiple Sclerosis Center (E.R., T.C., H.L.W., S.B., T.S.), Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (M.K.), Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Medical Physics Section (M.-A.P.), Radiology Department, University of Texas Southwestern Medical Center, Dallas, TX; Department of Neurology (J.K.), Brigham and Women's Hospital, Boston, MA; Ceretype Neuromedicine (E.S.), Cambridge, MA; Functional Neuroimaging Laboratory (D.S.), Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Nuclear Medicine (C.K.K.), Department of Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea; Biogen Inc. (J.L.), Cambridge, MA; and Department of Neurology (J.P.K.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
² From the PET Imaging Program in Neurologic Diseases (E.R., K.C., S.C., J.F., T.S.) and Brigham Multiple Sclerosis Center (E.R., T.C., H.L.W., S.B., T.S.), Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (M.K.), Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Medical Physics Section (M.-A.P.), Radiology Department, University of Texas Southwestern Medical Center, Dallas, TX; Department of Neurology (J.K.), Brigham and Women's Hospital, Boston, MA; Ceretype Neuromedicine (E.S.), Cambridge, MA; Functional Neuroimaging Laboratory (D.S.), Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Nuclear Medicine (C.K.K.), Department of Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea; Biogen Inc. (J.L.), Cambridge, MA; and Department of Neurology (J.P.K.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. tsinghal@bwh.harvard.edu.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Adult
Aged
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / immunology
Alzheimer Disease* / metabolism
Alzheimer Disease* / physiopathology
Autoantibodies
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / metabolism*
Demyelinating Autoimmune Diseases, CNS* / diagnostic imaging
Demyelinating Autoimmune Diseases, CNS* / immunology
Demyelinating Autoimmune Diseases, CNS* / metabolism
Demyelinating Autoimmune Diseases, CNS* / physiopathology
Electroencephalography
Encephalitis* / diagnostic imaging
Encephalitis* / immunology
Encephalitis* / metabolism
Encephalitis* / physiopathology
Female
Follow-Up Studies
Humans
Intracellular Signaling Peptides and Proteins* / immunology
Magnetic Resonance Imaging
Male
Mesencephalon / diagnostic imaging
Mesencephalon / metabolism*
Middle Aged
Positron-Emission Tomography
Putamen / diagnostic imaging
Putamen / metabolism*
Retrospective Studies
Young Adult

Substances

Autoantibodies
Intracellular Signaling Peptides and Proteins
LGI1 protein, human
anti-leucine-rich glioma-inactivated 1 autoantibody