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Neuroimage Clin. 2019 May 29;23:101875. doi: 10.1016/j.nicl.2019.101875. [Epub ahead of print]

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

Author information

1
Department of Medical and Health Sciences (IMH), Linköping University, 581 83 Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, 581 83 Linköping, Sweden.
2
Linköping University, 581 83 Linköping, Sweden.
3
Department of Pediatrics, Queen Silvia Children's Hospital, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, 416 50 Gothenburg, Sweden.
4
Center for Medical Image Science and Visualization, Linköping University, 581 83 Linköping, Sweden; Department of Clinical and Experimental Medicine (IKE), Linköping University, 581 83 Linköping, Sweden; Department of Neuroscience, Uppsala University, 752 36 Uppsala, Sweden.
5
Department of Clinical and Experimental Medicine (IKE), Linköping University, 581 83 Linköping, Sweden.
6
Department of Medical and Health Sciences (IMH), Linköping University, 581 83 Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, 581 83 Linköping, Sweden. Electronic address: maria.engstrom@liu.se.

Abstract

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.

KEYWORDS:

Locus coeruleus; Myelin; Neuromelanin; Orexin/hypocretin; Quantitative MRI (qMRI); Relaxation time

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