Feeling unreal: a functional imaging study in patients with Kleine-Levin syndrome.
Kleine-Levin syndrome is characterized by relapsing-remitting episodes of severe hypersomnia, cognitive impairment, apathy, derealization and behavioural disturbances. Between episodes, patients have normal sleep, mood and behaviour. Functional imaging studies performed in small series of patients with Kleine-Levin syndrome with visual or semi-quantitative, uncontrolled analysis yielded equivocal brain changes. Using whole brain voxel-based group analysis, we compared brain perfusion scintigraphy during and between episodes in consecutive patients with Kleine-Levin syndrome versus healthy control subjects and correlated perfusion changes with disease severity and symptoms, focusing on less studied but disabling symptoms, such as apathy and derealization. During asymptomatic periods, 41 patients (mean age of 22.3 ± 8.1 years, 56.1% male) and 15 age- and sex-matched healthy control subjects underwent single-photon emission computed tomography scanning with technetium-99m ethyl cysteinate dimer. Eleven patients repeated the test during a symptomatic period. Compared with controls, patients during asymptomatic periods had persistent hypoperfusion in the hypothalamus, the thalamus (mainly the right posterior part), the caudate nucleus, and cortical associative areas, including the anterior cingulate, (Brodmann area 25), the orbito-frontal (Brodmann area 11) and the right superior temporal cortices (Brodmann area 22), extending to the insula (P < 0.001 in all area). Two additional hypoperfused areas emerged during symptomatic periods (P < 0.001), located in the right dorsomedial prefrontal cortex (Brodmann area 8) and the right parieto-temporal junction (Brodmann areas 22 and 39). These two areas were more affected between episodes, when the mean episode duration was longer (r = -0.53; P < 0.001). The score for the Depersonalization/Derealization Inventory during symptomatic periods strongly correlated with the hypoperfusion of the right (r = -0.74, P < 0.001) and left (r = -0.59, P < 0.005) parieto-temporal junctions. No hyperperfusion was found. Because the parieto-temporal junction (including the angular gyrus) is involved in cross-modal association between somatosensory (body knowledge), auditory and visual information, the robust hypoperfusions and correlations observed in this area may underlie the striking derealization reported by patients during episodes. Defects in the dorsomedial prefrontal cortex may cause apathy. Persistent hypoperfusion in the diencephalic and associative cortical area during asymptomatic periods is a marker of the disease, suggestive of a scenario wherein patients compensate for these deficient circuitries.
1 Nuclear Medicine Department, Pitié-Salpêtrière University Hospital, APHP, Paris, France2 Sorbonne University, UPMC Univ Paris 06, Laboratoire d'Imagerie Fonctionnelle, INSERM UMR S 678, Paris, France isabelle.arnulf@psl.aphp.fr.
Aurelie
A
Kas
3 Sorbonne University, UPMC Univ Paris 06, Brain Research Institute (CRICM), Inserm UMR-S975, CNRS UMR7225, Paris, France4 Clinical investigation Centre Paris Est (CIC-9304), Paris, France5 Sleep Disorders Unit, National Reference Centre for Kleine-Levin Syndrome, Pitié-Salpêtrière University Hospital, APHP, Paris, France.
Sophie
S
Lavault
1 Nuclear Medicine Department, Pitié-Salpêtrière University Hospital, APHP, Paris, France2 Sorbonne University, UPMC Univ Paris 06, Laboratoire d'Imagerie Fonctionnelle, INSERM UMR S 678, Paris, France.
Marie-Odile
MO
Habert
3 Sorbonne University, UPMC Univ Paris 06, Brain Research Institute (CRICM), Inserm UMR-S975, CNRS UMR7225, Paris, France4 Clinical investigation Centre Paris Est (CIC-9304), Paris, France5 Sleep Disorders Unit, National Reference Centre for Kleine-Levin Syndrome, Pitié-Salpêtrière University Hospital, APHP, Paris, France isabelle.arnulf@psl.aphp.fr.
Isabelle
I
Arnulf
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D001931:Brain Mapping; D002648:Child; D003072:Cognition Disorders / Q000209:etiology; D003545:Cysteine / Q000031:analogs & derivatives; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017593:Kleine-Levin Syndrome / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D015609:Organotechnetium Compounds; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013223:Statistics as Topic; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
D015609:Organotechnetium Compounds; C059659:technetium Tc 99m bicisate; D003545:Cysteine
Kleine-Levin Syndrome; apathy; brain scintigraphy; derealization