Widespread Hypermetabolism in Symptomatic and Asymptomatic Episodes in Kleine-Levin Syndrome

Abstract

BackgroundNo reliable biomarkers are identified in KLS. However, few functional neuroimaging studies suggested hypoactivity in thalamic and hypothalamic regions during symptomatic episodes. Here, we investigated relative changes in regional brain metabolism in Kleine-Levin syndrome (KLS) during symptomatic episodes and asymptomatic periods, as compared to healthy controls.MethodsFour drug-free male patients with typical KLS and 15 healthy controls were included. 18-F-fluorodeoxy glucose positron emission tomography (PET) was obtained in baseline condition in all participants, and during symptomatic episodes in KLS patients. All participants were asked to remain fully awake during the whole PET procedure.ResultsBetween state-comparisons in KLS disclosed higher metabolism in paracentral, precentral, and postcentral areas, supplementary motor area, medial frontal gyrus, thalamus and putamen during symptomatic episodes, and decreased metabolism in occipital and temporal gyri. As compared to healthy control subjects, KLS patients in the asymptomatic phase consistently exhibited significant hypermetabolism in a wide cortical network including frontal and temporal cortices, posterior cingulate and precuneus, with no detected hypometabolism. In symptomatic KLS episodes, hypermetabolism was additionally found in orbital frontal and supplementary motor areas, insula and inferior parietal areas, and right caudate nucleus, and hypometabolism in the middle occipital gyrus and inferior parietal areas.ConclusionOur results demonstrated significant hypermetabolism and few hypometabolism in specific but widespread brain regions in drug-free KLS patients at baseline and during symptomatic episodes, highlighting the behavioral state-dependent nature of changes in regional brain activity in KLS.

Preliminary results on CSF biomarkers for hypothalamic dysfunction in Kleine–Levin syndrome

“…Our findings suggest that episodic hypothalamic dysfunction and state-dependent variations in hypocretin levels might occur in KLS, concurring with some functional neuroimaging findings [2,3,9,10]. Intermittent alteration of the diencephalic system may vary in degree between patients and between episodes, depending on the phenotype and its severity.…”

Serum cytokine levels in Kleine–Levin syndrome

“…This is supported by functional imaging studies during episodes, showing changes in activity in thalamic and hypothalamic regions, and in the frontal and temporal lobes [1,[3][4][5]. Analysis of case reports suggest that KLS has a genetic component [1,[6][7][8].…”

The Development of Sleep Medicine: A Historical Sketch

“…The method allows to compare brain metabolism in the same patient during symptomatic and asymptomatic episodes. 64 …”