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

Abstract

Background and ObjectivesThis [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.MethodsFDG-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.ResultsP-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.DiscussionSemiquantitative 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 EvidenceThis 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.

Whole‐brain metabolic pattern analysis in patients with anti‐leucine‐rich glioma‐inactivated 1 (LGI1) encephalitis

“…In this study, we investigated the anti-LGI1 AE metabolic pattern and identified hypermetabolism in the cerebellum, bilateral caudate nucleus, putamen, hippocampus and left Rolandic area, as well as hypometabolism in the left mPFC, in line with previous findings [13,25]. Previous semi-quantitative research showed hypermetabolism in the mesial temporal lobe structures and subcortical structures [26] or an increased metabolic ratio of putamen/global brain, putamen/thalamus and putamen/midbrain [27]. We applied voxel-based statistical t maps in a larger sample size to further validate the hypermetabolism in the above brain regions.…”

The Detection of Invisible Abnormal Metabolism in the FDG-PET Images of Patients With Anti-LGI1 Encephalitis by Machine Learning

“…These findings are consistent with previous studies about patients with anti-LGI1 encephalitis ( 6 , 28 , 29 ), suggesting that anti-LGI1 encephalitis is closely related to the metabolic abnormality in the medial temporal lobe and the basal ganglia. A recent study ( 7 ) also found that patients with anti-LGI1 encephalitis presented hypermetabolism in the medial temporal lobe and the basal ganglia (i.e., including the putamen and the caudate), consistent with the findings of the present study. However, some other brain regions showing metabolic abnormalities in the study ( 7 ) (e.g., angular gyrus, olfactory, and pons) were observed as normal regions in the present study.…”

“…A recent study ( 7 ) also found that patients with anti-LGI1 encephalitis presented hypermetabolism in the medial temporal lobe and the basal ganglia (i.e., including the putamen and the caudate), consistent with the findings of the present study. However, some other brain regions showing metabolic abnormalities in the study ( 7 ) (e.g., angular gyrus, olfactory, and pons) were observed as normal regions in the present study. It should be noted that, in the study ( 7 ), the mean of standardized uptake values across the regions of interest was used to measure the metabolic abnormalities.…”

“…However, some other brain regions showing metabolic abnormalities in the study ( 7 ) (e.g., angular gyrus, olfactory, and pons) were observed as normal regions in the present study. It should be noted that, in the study ( 7 ), the mean of standardized uptake values across the regions of interest was used to measure the metabolic abnormalities. In contrast, in this study, the independent images related to anti-LGI1 encephalitis were separated by ICA.…”

“…In fact, as suggested by a position paper ( 2 ), a preliminary treatment can be initiated by an early assessment based on some traditional clinical characteristics and commonly used methods of diagnosis, such as magnetic resonance imaging (MRI), electroencephalography (EEG), or cerebrospinal fluid (CSF), before obtaining the results of antibody testing, which, in turn, will refine the initial diagnosis and treatment. However, the MRI results in some patients with anti-LGI1 encephalitis were normal ( 5 – 7 ) and positron emission tomography (PET) can increase the sensitivity to LGI1 encephalitis compared to MRI ( 6 , 8 , 9 ). Therefore, PET may be a prospective imaging tool for the early diagnosis of LGI1 encephalitis.…”