Cerebral perfusion abnormality in narcolepsy with cataplexy Eun Yeon Joo, a,h Seung Bong Hong, a,h, * Woo Suk Tae, a,f Jee Hyun Kim, a,h Sun Jung Han, a,h Yong Won Cho, d,h Chang Ho Yoon, e,h Sung Ik Lee, i Mann Hyung Lee, j Kyung Han Lee, b Myoung-Hee Kim, g Byung Tae Kim, b and Leen Kim c a Department of Neurology, Samsung Medical Center and Center for Clinical Medicine, SBRI, Sungkyunkwan University School of Medicine, Seoul, Korea b Department of Nuclear Medicine, Samsung Medical Center and Center for Clinical Medicine, SBRI, Sungkyunkwan University School of Medicine, Seoul, Korea c Department of Psychiatry, Anam Hospital, College of Medicine, Korea University, Seoul, Korea d Department of Neurology, Dongsan Medical Center, Keimyung University, Daegu, Korea e Department of Neurology, College of Medicine, Inha University, Incheon, Korea f Department of Bioengineering, Hanyang University, Seoul, Korea g Department of Computer Science and Engineering, Ewha Woman’s University, Seoul, Korea h Korean Sleep Society, Korea i Department of Neurology, Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea j College of Pharmacy, Catholic University of Daegue, Gyongbook, Korea Received 21 January 2005; revised 21 March 2005; accepted 10 June 2005 Available online 10 August 2005 To investigate abnormal cerebral perfusion in narcoleptics with cataplexy, 25 narcoleptics with cataplexy and 25 normal controls were enrolled in this study. Cerebral perfusion was measured by brain single photon emission computed tomography (SPECT) using 99m Tc-ethyl- cysteinate dimer. Patients and normal controls had not received any medication prior to the SPECT scan. Differences in cerebral perfusion between narcoleptics and normal controls were subjected to statistical parametric mapping (SPM) analysis. Overnight polysomnography and multiple sleep latency test (MSLT) were performed in all patients. Brain SPECT was carried out on all patients and normal controls during the waking state. Clinical symptoms and MSLT results of all patients are in accord with the International Classification of Sleep Disorders criteria for narcolepsy. MSLTshowed a short mean sleep latency (1.69 T 1.0 min) and 2 – 5 sleep onset REM periods in individual patient. SPM analysis of brain SPECT showed hypoperfusion of the bilateral anterior hypothal- ami, caudate nuclei, and pulvinar nuclei of thalami, parts of the dorsolateral/ventromedial prefrontal cortices, parahippocampal gyri, and cingulate gyri in narcoleptics [ P < 0.05 by Student’s t test with false discovery rate (FDR) correction]. Significant hypoperfusion in the white matter of frontal and parietal lobes was also noted in narcoleptics. This study shows reduced cerebral perfusion in subcortical structures and cortical areas in narcoleptics. The distribution of abnormal cerebral perfusion is concordant with the pathway of the cerebral hypocretin system and may explain the characteristic features of narcolepsy, i.e., cataplexy, emotional lability, and attention deficit. D 2005 Elsevier Inc. All rights reserved. Keywords: Narcolepsy; Cerebral perfusion; 99m Tc-ethylcysteinate dimer (ECD); SPECT; Hypothalamus Introduction Narcolepsy is characterized by excessive daytime sleepiness (EDS), a disruption of sleep – wake behavior, cataplexy (sudden loss of muscle tone provoked by emotional stimuli), and the other rapid eye movement (REM) sleep phenomena such as sleep paralysis and hypnagogic hallucination (de Lecea et al., 1998; Joo et al., 2004a). Hypocretin-containing neuron numbers are reduced in the hypothalamus of the narcoleptic brain (Thannickal et al., 2000). The neuropeptide hypocretin appears to play a critical role in the neurobiology of narcolepsy (Sakurai et al., 1998; Nishino et al., 2000; Taheri et al., 2002). Several brain MRI studies had been performed to identify the structural abnormalities of narcolepsy, but results have been controversial. A recent voxel-based morpho- metric study revealed reduced gray matter concentrations in the hypothalamus and nucleus accumbens (Draganski et al., 2002). But another study failed to find any gray matter change in brain structures including the hypothalamus (Overeem et al., 2003). Other authors have reported reductions in bilateral cortical gray matter, predominantly in the inferior temporal and inferior frontal regions (Kaufmann et al., 2002). To elucidate the pathophysiology of narcolepsy, brain single photon emission computed tomography (SPECT) and positron 1053-8119/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2005.06.019 * Corresponding author. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. Fax: +82 2 3410 0052. E-mail address: sbhong@smc.samsung.co.kr (S.B. Hong). Available online on ScienceDirect (www.sciencedirect.com). www.elsevier.com/locate/ynimg NeuroImage 28 (2005) 410 – 416