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Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy


Poryazova, R; Schnepf, B; Werth, E; Khatami, R; Dydak, U; Meier, D; Boesiger, P; Bassetti, C L (2009). Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy. Sleep, 32(5):607-613.

Abstract

STUDY OBJECTIVES: Proton resonance spectroscopy (1H-MRS) allows noninvasive chemical tissue analysis in the living brain. As neuronal loss and gliosis have been described in narcolepsy, metabolites of primary interest are N-acetylaspartate (NAA), a marker of neuronal integrity and myo-Inositol (ml), a glial marker and second messenger involved in the regulation of intracellular calcium. One 1H-MRS study in narcolepsy found no metabolic changes in the pontomedullary junction. Another study showed a reduction in NAA/creatine-phosphocreatine (Cr) in the hypothalamus of narcolepsy patients with cataplexy. We aimed to test for metabolic changes in specific brain areas, "regions of interest," thought to be involved in emotional processing, sleep regulation and pathophysiology of narcolepsy: hypothalamus, pontomesencephalic junction and both amygdalae. DESIGN: We performed 1H-MRS using a 3T Philips Achieva whole body MR scanner. Single-voxel proton MR spectra were acquired and quantified with LCModel to determine metabolite concentration ratios. SETTING: The participants in the study were recruited at the outpatient clinic for sleep medicine, Department of Neurology and magnetic resonance spectroscopy was performed at the MRI facility, University Hospital Zurich. PARTICIPANTS: 1H-MRS was performed in fourteen narcolepsy patients with cataplexy, CSF hypocretin deficiency (10/10) and HLA-DQB1*0602 positivity (14/14) and 14 age, gender and body mass index matched controls. Patients were treatment naïve or off therapy for at least 14 days before scanning. MEASUREMENTS AND RESULTS: No differences were observed in the regions of interest for (total NAA)/Cr ratios. Myo-Inositol (ml)/Cr was significantly lower in the right amygdala of the patients, compared to controls (P < 0.042). Significant negative correlations only in the patients group were found between (total NAA)/Cr in hypothalamus and ml/Cr in the right amygdala (r = -0.89, P < 0.001), between ml/Cr in hypothalamus and (total NAA)/Cr in the right amygdala (r = -63, P < 0.05) and between ml/Cr in the left amygdala and total NAA)/Cr in the pontomesencephalic junction (r = -0.69, P < 0.05). CONCLUSION: Our findings suggest amygdala involvement and possible hypothalamo-amygdala dysfunction in narcolepsy.

STUDY OBJECTIVES: Proton resonance spectroscopy (1H-MRS) allows noninvasive chemical tissue analysis in the living brain. As neuronal loss and gliosis have been described in narcolepsy, metabolites of primary interest are N-acetylaspartate (NAA), a marker of neuronal integrity and myo-Inositol (ml), a glial marker and second messenger involved in the regulation of intracellular calcium. One 1H-MRS study in narcolepsy found no metabolic changes in the pontomedullary junction. Another study showed a reduction in NAA/creatine-phosphocreatine (Cr) in the hypothalamus of narcolepsy patients with cataplexy. We aimed to test for metabolic changes in specific brain areas, "regions of interest," thought to be involved in emotional processing, sleep regulation and pathophysiology of narcolepsy: hypothalamus, pontomesencephalic junction and both amygdalae. DESIGN: We performed 1H-MRS using a 3T Philips Achieva whole body MR scanner. Single-voxel proton MR spectra were acquired and quantified with LCModel to determine metabolite concentration ratios. SETTING: The participants in the study were recruited at the outpatient clinic for sleep medicine, Department of Neurology and magnetic resonance spectroscopy was performed at the MRI facility, University Hospital Zurich. PARTICIPANTS: 1H-MRS was performed in fourteen narcolepsy patients with cataplexy, CSF hypocretin deficiency (10/10) and HLA-DQB1*0602 positivity (14/14) and 14 age, gender and body mass index matched controls. Patients were treatment naïve or off therapy for at least 14 days before scanning. MEASUREMENTS AND RESULTS: No differences were observed in the regions of interest for (total NAA)/Cr ratios. Myo-Inositol (ml)/Cr was significantly lower in the right amygdala of the patients, compared to controls (P < 0.042). Significant negative correlations only in the patients group were found between (total NAA)/Cr in hypothalamus and ml/Cr in the right amygdala (r = -0.89, P < 0.001), between ml/Cr in hypothalamus and (total NAA)/Cr in the right amygdala (r = -63, P < 0.05) and between ml/Cr in the left amygdala and total NAA)/Cr in the pontomesencephalic junction (r = -0.69, P < 0.05). CONCLUSION: Our findings suggest amygdala involvement and possible hypothalamo-amygdala dysfunction in narcolepsy.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biomedical Engineering
04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Language:English
Date:2009
Deposited On:29 Jun 2009 07:50
Last Modified:05 Apr 2016 13:17
Publisher:Associated Professional Sleep Societies, LLC
ISSN:0161-8105
PubMed ID:19480227
Permanent URL: http://doi.org/10.5167/uzh-19471

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