Accepted Manuscript Hypersomnia due to injury of the lower ventral ascending reticular activating system in a patient with intraventricular hemorrhage Sung Ho Jang, MD, Young Hyeon Kwon, BS PII: S1389-9457(18)30203-X DOI: 10.1016/j.sleep.2018.05.016 Reference: SLEEP 3707 To appear in: Sleep Medicine Received Date: 19 February 2018 Revised Date: 1 May 2018 Accepted Date: 22 May 2018 Please cite this article as: Jang SH, Kwon YH, Hypersomnia due to injury of the lower ventral ascending reticular activating system in a patient with intraventricular hemorrhage, Sleep Medicine (2018), doi: 10.1016/j.sleep.2018.05.016. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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ACCEPTED MANUSCRIPT Title: Hypersomnia due to injury of the lower ventral ascending reticular activating system in a patient with intraventricular hemorrhage Running title: Hypersomnia following intraventricular hemorrhage RI PT Author 1: Sung Ho Jang, MD Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University SC Mailing Address: Department of Physical Medicine and Rehabilitation, College of Medicine, Tel: 82-53-620-4098 M AN U Yeungnam University 317-1, Daemyungdong, Namku, Taegu, 705-717, Republic of Korea FAX: 82-53-625-3508 e-mail: strokerehab@hanmail.net Author 2 (Corresponding author): Young Hyeon Kwon, Bs Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University TE D Mailing Address: Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University 317-1, Daemyungdong, Namku, Daegu, 705-717, Republic of Korea e-mail: kyh7648764@daum.net EP Acknowledgements AC C This work was supported by the DGIST R&D Program of the Ministry of Science, ICT and Future Planning (18-BD-0401). Disclosures Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. ACCEPTED MANUSCRIPT Key words Hypersomnia, Intraventricular haemorrhage, Diffusion tensor tractography, Ascending AC C EP TE D M AN U SC RI PT reticular activating system ACCEPTED MANUSCRIPT 1. Introduction to the case A 74-year-old female underwent extraventricular drainage for an intraventricular haemorrhage (IVH) at the neurosurgery department of a university hospital (Fig. 1-A). She RI PT exhibited severe hypersomnia following IVH onset. At four weeks after onset, she was transferred to the rehabilitation department of the same hospital to undergo rehabilitation. Except for approximately three hours during daytime, she remained asleep. Her sleep SC abnormality was indicated as severe hypersomnia on the Epworth Sleepiness Scale (score = M AN U 23; maximum score = 24; cut off for severe hypersomnia = 10) [1]. 2. Image analysis Diffusion tensor imaging data were acquired at four weeks after IVH onset by using a 1.5 T Philips Gyroscan Intera (Philips, Best, Netherlands). Two portions of the ascending TE D reticular activating system (ARAS) were reconstructed by selecting fibres passing through regions of interest (ROIs). For analysis of the lower dorsal ARAS, the seed ROI was placed on the pontine reticular formation (RF), and the target ROI with the option of termination was EP placed on the intralaminar thalamic nucleus (ILN) [2]. For reconstruction of the lower ventral ARAS the seed ROI was placed on the pontine RF and the target ROI with the option of AC C termination was placed on the hypothalamus [2]. Out of 5000 samples generated from a seed voxel, results were visualized at a threshold of 2 streamlined through each voxel for analysis. The lower ventral ARAS was not reconstructed on either sides, whereas the lower dorsal ARAS was well-reconstructed on both sides. Figure 1 3. Discussion ACCEPTED MANUSCRIPT Since Moruzzi and Magoun’s study in 1949, the ARAS has been considered as a crossroad of arousal regulation [3]. Using diffusion tensor tractography, we evaluated the patient’s two lower portions of the ARAS: the lower dorsal ARAS between the pontine RF, RI PT the thalamic ILN, and the lower ventral ARAS between the pontine RF and the hypothalamus. We observed that the lower ventral ARAS was not reconstructed on either side, indicating severe injuries of both lower ventral ARAS. Based on our results and several SC studies which reported a close association between the hypothalamus and hypersomnia, as well as that injuries of the lower ventral ARAS are closely related to hypersomnia; the M AN U hypersomnia in this patient appears to be mainly ascribable to injury of the lower ventral ARAS [2,4,5]. Furthermore, the pathophysiological mechanism of injury of the lower portion of the ARAS in this patient appears to be related to the pathogenic mechanism of the neural injury resulting from the hematomas in the intraventricles (third and fourth ventricles). TE D Previous studies have suggested that injury to periventricular white matter could occur through mechanical (increased intracranial pressure or direct mass) or chemical injury mechanisms of hematomas (as a blood clot itself can cause extensive damage). In this study, EP considering the normal configuration of the lower dorsal ARAS, which passes the pontine tegmentum along with the lower ventral ARAS close to the fourth ventricle, the injury of the AC C patient’s lower ventral ARAS appears to be mainly ascribed to the hematoma in the third ventricle adjacent to the hypothalamus. ACCEPTED MANUSCRIPT References [1] Bloch KE, Schoch OD, Zhang JN et al., German version of the epworth sleepiness scale. Respiration 1999;66:440-47. https://doi.org/10.1159/000029408. Jang SH, Chang CH, Jung YJ et al., Post-stroke hypersomnia. Int J Stroke RI PT [2] 2016;11:Np5-Np6. https://doi.org/10.1177/1747493015607502. Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol http://dx.doi.org/10.1016/0013-4694(49)90219-9. Jang SH, Lee HD, Chang CH et al., Recovery of hypersomnia concurrent with M AN U [4] 1949;1:455-73. SC [3] recovery of an injured ascending reticular activating system in a stroke patient: A case report. Medicine (Baltimore) 2016;95:e2484. https://doi.org/10.1097/md.0000000000002484. reticular TE D Jang SH, Seo WS, Kwon HG. Post-traumatic narcolepsy and injury of the ascending activating system. EP https://doi.org/10.1016/j.sleep.2015.09.020. AC C [5] Sleep Med 2016;17:124-25. ACCEPTED MANUSCRIPT Figure Legend Fig. 1. A. Brain computed tomography images at onset show haematomas in the intraventricles of RI PT the third and fourth ventricles. T2-weighted brain magnetic resonance images at four weeks after onset reveal no abnormal lesion around the third and fourth ventricles. B. Results of diffusion tensor tractography (DTT) for the patient: normal configuration of SC the lower dorsal ascending reticular activating system and non-reconstruction (arrows) of both the lower ventral ascending reticular activating system compared with a normal AC C EP TE D M AN U subject (67-year-old female). AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT