title: Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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).
  
  
  CONCLUSIONS
  Our findings suggest amygdala involvement and possible hypothalamo-amygdala dysfunction in narcolepsy.
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Rositsa
authors.initials: R
authors.lastname: Poryazova
authors.forename: Betina
authors.initials: B
authors.lastname: Schnepf
authors.forename: Esther
authors.initials: E
authors.lastname: Werth
authors.forename: Ramin
authors.initials: R
authors.lastname: Khatami
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dydak
authors.forename: Dieter
authors.initials: D
authors.lastname: Meier
authors.forename: Peter
authors.initials: P
authors.lastname: Boesiger
authors.forename: Claudio L
authors.initials: CL
authors.lastname: Bassetti
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002385:Cataplexy / Q000175:diagnosis / Q000503:physiopathology*; D003401:Creatine / Q000378:metabolism; D004292:Dominance, Cerebral / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology*; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008636:Mesencephalon / Q000503:physiopathology; D009290:Narcolepsy / Q000175:diagnosis / Q000503:physiopathology*; D011149:Pons / Q000503:physiopathology; D012016:Reference Values
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine