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

Journal article
Authors N. M. Drissi
M. Warntjes
A. Wessén
Attila Szakacs
Niklas Darin
Tove Hallböök
A. M. Landtblom
H. Gauffin
M. Engström
Published in NeuroImage: Clinical
Volume 23
ISSN 2213-1582
Publication year 2019
Published at Institute of Clinical Sciences, Department of Pediatrics
Language en
Keywords Locus coeruleus, Myelin, Neuromelanin, Orexin/hypocretin, Quantitative MRI (qMRI), Relaxation time, fluoxetine, levothyroxine, methylphenidate, modafinil, orexin, oxybate sodium, sertraline, zolpidem, adolescent, adult, Article, cataplexy, clinical article, controlled study, female, human, locus ceruleus, male, narcolepsy, nuclear magnetic resonance imaging, priority journal, reticular formation, sleep time, superior cerebellar peduncle, young adult
Subject categories Pediatrics, Pharmacology and Toxicology


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. © 2019 The Authors

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