Functional magnetic resonance imaging in narcolepsy and the kleine-levin syndrome

Maria Engström, Tove Hallböök, Attila Szakacs, Thomas Karlsson, Anne-Marie Landtblom, Maria Engström, Tove Hallböök, Attila Szakacs, Thomas Karlsson, Anne-Marie Landtblom

Abstract

This work aims at reviewing the present state of the art when it comes to understanding the pathophysiology of narcolepsy and the Kleine-Levin syndrome (KLS) from a neuroimaging point of view. This work also aims at discussing future perspectives of functional neuroimaging in these sleep disorders. We focus on functional magnetic resonance imaging (fMRI), which is a technique for in vivo measurements of brain activation in neuronal circuitries under healthy and pathological conditions. fMRI has significantly increased the knowledge on the affected neuronal circuitries in narcolepsy and the Kleine-Levin syndrome. It has been shown that narcolepsy is accompanied with disturbances of the emotional and the closely related reward systems. In the Kleine Levin syndrome, fMRI has identified hyperactivation of the thalamus as a potential biomarker that could be used in the diagnostic procedure. The fMRI findings in both narcolepsy and the Kleine-Levin syndrome are in line with previous structural and functional imaging studies. We conclude that fMRI in combination with multi-modal imaging can reveal important details about the pathophysiology in narcolepsy and the Kleine-Levin syndrome. In the future, fMRI possibly gives opportunities for diagnostic support and prediction of treatment response in individual patients.

Keywords: Kleine–Levin syndrome; ascending arousal system; functional magnetic resonance imaging; hypersomnia; hypothalamus; narcolepsy; sleep; thalamus.

Figures

Figure 1
Figure 1
Brain activation in Kleine–Levin syndrome (KLS) during working memory performance. The orange areas show typical working memory activation in the executive network in healthy individuals. Pink areas show regions with hyperactivation in KLS patients. The main finding of thalamic hyperactivation is marked with a pink arrow. The white arrow marks areas within the orange activation cluster in the anterior cingulate cortex and adjacent medial prefrontal cortex where KLS patients had less activation compared to the healthy control group. Data include 18 KLS patients and 18 matched controls (23).
Figure 2
Figure 2
The ascending arousal system involved in regulation of sleep and wakefulness. (A) The figure is a schematic description of the ventral (red) and dorsal (blue) pathways of the ascending arousal system. BF = basal forebrain, Thal = thalamus, PAG = periaqueductal gray, Raphe = Raphe nuclei, LC = locus coeruleus, TEG = tegmentum, RF = reticular formation. (B). The figure shows brain activation in one male narcolepsy patient during emotional flanker task (57) in emotional and sleep regulating networks. OFC = orbitofrontal cortex, vAIC = ventral anterior insular cortex, mPFC = medial prefrontal cortex, PCC = posterior cingulate cortex, PC = precuneus, Hyp = hypothalamus, Thal = thalamus, dTEG = dorsal tegmentum.

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