Kleine-Levin syndrome is a rare disorder characterized by relapsing-remitting episodes of severe hypersomnia, cognitive impairment, apathy, derealization and behavioural disturbances. Between episodes, most patients experience normal sleep, mood and behaviour, but they may have some residual abnormalities in brain functional imaging; however, the frequency, localisation and significance of abnormal imaging is unknown, as brain functional imaging have been scarce and heterogenous (including scintigraphy, [18F] fluorodeoxyglucose positron emission tomography/computerized tomography [FDG-PET/CT] and functional MRI during resting state and cognitive effort) and based on case reports or on group analysis in small groups. Using visual individual analysis of FDG-PET/CT at the time of Kleine-Levin syndrome diagnosis, we examined the frequency, localisation and clinical determinants of hypo- and hypermetabolism in a cross-sectional study. Among 179 patients with Kleine-Levin syndrome who underwent FDG-PET/CT, the visual analysis was restricted to the 138 untreated patients studied during asymptomatic periods. As many as 70% of patients had hypometabolism, mostly affecting the posterior associative cortex and the hippocampus. Hypometabolism was associated with younger age, recent (<3 y) disease course, and a higher number of episodes during the preceding year. The hypometabolism was more extensive (from the left temporo-occipital junction to the entire homolateral and then the bilateral posterior associative cortex) at the beginning of the disorder. In contrast, there was hypermetabolism in the prefrontal dorsolateral cortex in half of the patients (almost all having concomitant hypometabolism in the posterior areas), which was also associated with younger age and shorter disease course. The cognitive performances (including episodic memory) were similar in patients with vs. without hippocampus hypometabolism. In conclusion, hypometabolism is frequently observed upon individual visual analysis of FDG-PET/CT during asymptomatic Kleine-Levin syndrome periods; it is mostly affecting the posterior associative cortex and the hippocampus and is mostly in young patients with recent onset disease. Hypometabolism provides a trait marker during the first years of Kleine-Levin syndrome, which could help clinicians during the diagnosis process.

Objectives: F-DOPA PET is used in glioma follow-up after radiotherapy to discriminate treatment-related changes (TRC) from tumour progression (TP). We compared the performances of a combined PET and MRI analysis with F-DOPA current standard of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation interpretation. Methods : We included 76 consecutive patients showing at least one gadolinium-enhancing lesion on T1-w MRI sequence (T1G). Two nuclear medicine physicians blindly analysed PET/MRI images. In addition to the conventional PET analysis, they looked for F-DOPA uptake(s) outside T1G-enhancing areas (T1G-/PET), in the white matter (WM/PET), for T1G-enhancing lesion(s) without sufficiently concordant F-DOPA uptake (T1G+/PET), and for F-DOPA uptake(s) away from haemorrhagic changes as shown with a Susceptibility Weighted Imaging sequence (SWI/PET). We measured lesions' F-DOPA uptake using healthy brain background (TBR) and striatum (T/S) as references, and lesions' perfusion with arterial spin labelling cerebral blood flow maps (rCBF). Scores were determined by logistic regression. Results: 53 and 23 patients were diagnosed with TP and TRC, respectively. The accuracies were 74% for T/S, 76% for TBR, and 84% for rCBF, with best cut-off values of 1.3, 3.7 and 1.25, respectively. For hybrid variables, best accuracies were obtained with conventional analysis (82%), T1G+/PET (82%) and SWI/PET (81%). T1G+/PET, SWI/PET and rCBF ≥ 1.25 were selected to construct a 3-point score. It outperformed conventional analysis and rCBF with an AUC of 0.94 and an accuracy of 87%. Conclusions : Our scoring approach combining F-DOPA PET and MRI provided better accuracy than conventional PET analyses for distinguishing TP from TRC in our patients after radiation therapy. Response to Reviewers:Once again, we would like to thank the reviewers and the editorial team for their work.As requested, the manuscript was fully checked with the Grammarly software and modified accordingly.