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PLoS One. 2014 Apr 3;9(4):e93813. doi: 10.1371/journal.pone.0093813. eCollection 2014.

Widespread hypermetabolism in symptomatic and asymptomatic episodes in Kleine-Levin syndrome.

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Service de Neurologie, Hôpital Gui-de-Chauliac, CHU Montpellier, Montpellier, France; Centre de Référence Nationale Maladie Rare, Narcolepsie et Hypersomnie Idiopathique, Montpellier, France; Inserm U1061, Montpellier, France.
Service de Médecine Nucléaire, Hôpital Gui-de-Chauliac, CHU Montpellier, Montpellier, France.
UR2NF, Neuropsychology and Functional Neuroimaging Research Unit, Université Libre de Bruxelles, Bruxelles, Belgium.



No 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.


Four 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.


Between 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.


Our 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.

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