New hypothesis on pontine–frontal eye field connectivity in Kleine–Levin syndrome

Engström, Maria; Landtblom, Anne‐Marie; Karlsson, Thomas

doi:10.1111/jsr.12428

Cited by 5 publications

(13 citation statements)

References 19 publications

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“…However, asymptomatic KLS patients as compared with healthy controls showed no difference in thalamic connectivity during rest. In addition, KLS patients had significantly reduced functional connectivity between dorsal pons and the frontal eye field; an area of the brain not only involved in cerebral control of eye movements but also involved in attention and working memory (Engström and others 2016). Given the lack of evidence, further neuroimaging research investigating brainstem involvement in KLS is warranted.…”

Section: Clinical Features and Pathogenesis Of Klsmentioning

confidence: 99%

Neuroimaging of Narcolepsy and Primary Hypersomnias

et al. 2020

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Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical features of narcolepsy and primary hypersomnias.

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Section: Clinical Features and Pathogenesis Of Klsmentioning

confidence: 99%

Neuroimaging of Narcolepsy and Primary Hypersomnias

et al. 2020

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“…In the literature search, we found 12 original articles on neuroimaging in KLS published 2013–2018, whereof five articles were case reports [ 7 , 8 , 9 ••, 10 – 18 ] (Table 1 ). Most studies report deviant function in the form of hypoperfusion, glucose hypermetabolism, or increased BOLD responses in frontotemporal areas (Fig.…”

Section: Recent Neuroimaging Findings In Klsmentioning

confidence: 99%

“…No difference in thalamic connectivity. Engström et al , 2016 [ 9 ••] FDG-PET 1 KLS Symptomatic Decreased glucose metabolism in bilateral thalami. Xie et al , 2016 [ 10 ] SPECT 41 KLS, 15 HC Symptomatic and asymptomatic General hypoperfusion in hypothalamus, thalamus, caudate, and anterior cingulate, orbito-frontal and temporal cortices.…”

Section: Recent Neuroimaging Findings In Klsmentioning

confidence: 99%

“…One resting-state fMRI study including 12 asymptomatic KLS patients and 14 healthy controls reports that KLS patients have reduced functional connectivity between the dorsal pons and the frontal eye field in Brodmann area (BA) 8 [ 9 ••]. Kas et al report decreased perfusion in BA 8 in symptomatic KLS patients and inverse correlation between perfusion in this area and mean duration of the sleep episodes [ 11 ].…”

Section: Recent Neuroimaging Findings In Klsmentioning

confidence: 99%

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Neuroimaging in the Kleine-Levin Syndrome

Engström

Latini

Landtblom

2018

Curr Neurol Neurosci Rep

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Purpose of ReviewThe purpose was to review the most recent literature on neuroimaging in the Kleine-Levin syndrome (KLS). We aimed to investigate if frontotemporal and thalamic dysfunction are key KLS signatures, and if recent research indicates other brain networks of interest that elucidate KLS symptomatology and aetiology.Recent FindingsIn a comprehensive literature search, we found 12 original articles published 2013–2018. Most studies report deviations related to cerebral perfusion, glucose metabolism, or blood-oxygen-level-dependent responses in frontotemporal areas and/or the thalamus. Studies also report dysfunction in the temporoparietal junction and the oculomotor network that also were related to clinical parameters. We discuss these findings based on recent research on thalamocortical networks and brain stem white matter tracts.SummaryThe hypothesis of frontotemporal and thalamic involvement in KLS was confirmed, and additional findings in the temporoparietal junction and the oculomotor system suggest a broader network involvement, which can be investigated by future high-resolution and multimodal imaging.

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“…The area here identified as SMA is identical with the supplementary eye field according to a meta-analysis on saccades by Jamadar et al ( Jamadar et al, 2013 ) . A recent study by us also found brainstem-frontal eye fields connectivity differences between patients with periodic idiopathic hypersomnia, the Kleine-Levin Syndrome (KLS), and healthy controls (Engstrom et al, 2016). The eventual implications of the oculomotor system in patients with sleep disorders have to be evaluated in future studies.…”

Section: Discussionmentioning

confidence: 78%

Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin

Drissi

Warntjes

Wessen

et al. 2019

NeuroImage: Clinical

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The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy ( n = 14) and healthy controls ( n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s −1 whereas healthy controls had a mean R2 of 1.31 s −1 , which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients.

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New hypothesis on pontine–frontal eye field connectivity in Kleine–Levin syndrome

Cited by 5 publications

References 19 publications

Neuroimaging of Narcolepsy and Primary Hypersomnias

Neuroimaging of Narcolepsy and Primary Hypersomnias

Neuroimaging in the Kleine-Levin Syndrome

Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin

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