Thalamic activation in the Kleine-Levin syndrome

Abstract

Study objectives: The objective of this study was to investigate if combined measures of activation in the thalamus and working memory capacity could guide the diagnosis of Kleine-Levin Syndrome (KLS). A second objective was to obtain more insight into the neurobiological causes of KLS.

Design: Matched group and consecutive recruitment.

Setting: University hospital neurology department and imaging center.

Patients or participants: Eighteen patients with KLS diagnosed according to the International Classification of Sleep Disorders and 26 healthy controls were included.

Interventions: N/A.

Measurements and results: Working memory capacity was assessed by the listening span task. A version of this task (reading span) was presented to the participants during functional magnetic resonance imaging (fMRI). Activation in the thalamus was measured in a region of interest analysis. A combination of the working memory capacity and the thalamic activation measures resulted in 80% prediction accuracy, 81% sensitivity, and 78% specificity regarding the ability to separate KLS patients from healthy controls. The controls had an inverse relation between working memory capacity and thalamic activation; higher performing participants had lower thalamic activation (r = -0.41). KLS patients showed the opposite relationship; higher performing participants had a tendency to higher thalamic activation (r = -0.35).

Conclusions: This study shows that functional neuroimaging of the thalamus combined with neuropsychological assessment of working memory function provides a means to guide diagnosis of Kleine-Levin Syndrome. Results in this study also indicate that imaging of brain function and evaluation of cognitive capacity can give insights into the neurobiological mechanisms of Kleine-Levin Syndrome.

Keywords: Functional magnetic resonance imaging (fMRI); hypersomnia; narcolepsy; thalamus; working memory.

Figure 1

(A) The number of correct responses during the pre-fMRI working memory task. The dashed line indicates the reference value (KLS mean value) = 15.2. (B) Thalamic activation during the most difficult level of the working memory task (Level 4). The dashed line represents the reference value (KLS mean value) = 50.9. (C) Working memory scores plotted against thalamic activation.

Figure 2

Brain activation during the working memory task in healthy controls (A) and KLS patients (B). The sagittal images show the levels of the displayed axial images in inferior-superior direction. The numbers above each axial slice represents the z coordinate in Montreal Neurological Institute (MNI) space. L = left hemisphere.

Figure 3

(A) Brain activation in the left thalamus region of interest present in KLS patients but not in the controls. (B) The image shows the area from which the thalamic activation was calculated. The region included the peak activation of the present results.

Figure 4

Brain activation during the working memory task in KLS patients at the first (yellow) and second (blue) examination. Coinciding activation clusters are displayed in green. The sagittal image shows the levels of the displayed axial images in inferior-superior direction. The numbers above each axial slice represents the z coordinate in Montreal Neurological Institute (MNI) space. L = left hemisphere. For visualization purpose the activation images are thresholded at P = 0.005.