Functional brain imaging using 18F-fluorodeoxyglucose positron emission tomography/computerized tomography in 138 patients with Kleine–Levin syndrome: an early marker?

Abstract

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.

Neuroimaging in the Rare Sleep Disorder of Kleine–Levin Syndrome: A Systematic Review

“…We found 10 observational studies that specifically discussed the role of functional imaging in patients with K.L.S. ; Table 2 shows the main characteristics of the studies [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

“…The increased of activity was presented mostly in the thalamus and prefrontal cortex. Table 3 shows the main findings in each study [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

“…between patients and controls is an argument against a primary thalamic dysfunction. Table 4 shows the bias analysis of the study [ 14 , 15 , 17 , 18 , 19 , 20 , 22 , 23 ].…”

“…In Dudoignon et al’s study, more patients with hippocampal hypometabolism had working memory deficits than those without hippocampal metabolism [ 19 ]. Executive functions, attention, and episodic verbal memory were preserved, suggesting that other areas of the brain compensate for the hypometabolism of the hypothalamus [ 19 ].…”

“…In the Dudoignon study, hypometabolism in the posterior associative cortex and hippocampus and increased metabolism in the prefrontal cortex was associated with the younger onset of age and shorter course of the disease [ 19 ]. Hypometabolism in the posterior associative cortex was also associated with a shorter course of the disease, and the association with the female sex was strong.…”