[18F]Fludeoxyglucose-Positron Emission Tomography Evidence for Cerebral Hypermetabolism in the Awake State in Narcolepsy and Idiopathic Hypersomnia (original) (raw)
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Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical featu...
Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy
Sleep, 2009
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. 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 d...
Cns & Neurological Disorders-drug Targets, 2009
Neuroimaging techniques have refined the characterization of neural structures involved in the regulation of normal sleep-wake cycle in healthy humans. Yet brain imaging studies in patients with sleep disorders still remain scarce. In narcoleptic patients, structural and functional brain imaging studies have suggested the involvement of the hypothalamus in the pathophysiology of narcolepsy, plausibly consistent with an impairment of the hypocretin-orexin system. Some recent studies have further suggested that cataplexy, a key feature of the narcoleptic syndrome, might result from a dysfunction of the hypothalamus and its interactions with limbic structures. Other neuroimaging studies have focused on the assessment of neurotransmission and the effects of pharmacological treatment in narcoleptic patients. However, the neural correlates of some main symptoms of narcolepsy, such as sleep attacks, hypnagogic/hypnopompic hallucinations and sleep paralysis, are still unknown. In addition, the description of brain activity patterns during sleep in narcoleptic patients needs further investigation. Neuroimaging has proven to be a valuable tool for the study of sleep regulation and sleep disorders; its future developments will undoubtedly improve our understanding of the neural mechanisms underlying narcolepsy with cataplexy.
Neuroimaging in Sleep and Sleep Disorders
Elsevier eBooks, 2009
Brain imaging studies have provided key insights into the neural causes, consequences and correlates of sleep disorders. During normal sleep, functional neuroimaging data revealed specific changes in regional brain activity correlated with electroencephalographic sleep oscillations. Neuroimaging studies in insomnia support the global hyperarousal hypothesis, by showing decreased inhibition during the transition from wakefulness to sleep. In narcoleptic patients, both functional and structural abnormalities were found in the hypothalamus, supporting a hypocretinergic dysfunction, whereas altered limbic responses may relate to emotional dysregulation contributing to the onset of cataplectic episodes. In idiopathic hypersomnia, recent neuroimaging data suggest the presence of incomplete sleep-wake transitions in relationship with the severity of excessive daytime sleepiness. Lastly, functional and structural neuroimaging studies of rapid-eye-movement sleep behavior disorder converged on pontine abnormalities, as well as presynaptic dopamine dysfunction related to the development of synucleinopathy.
Neuroimaging findings in primary insomnia
Pathologie Biologie
Les techniques d’imagerie cérébrale ont permis des avancées considérables dans l’étude du sommeil chez l’humain. Cependant, les études par imagerie cérébrale dans l’insomnie primaire demeurent peu nombreuses, particulièrement en regard de la prévalence importante de ce trouble du sommeil dans la population générale. Cette revue examine la contribution des études d’imagerie cérébrale fonctionnelle et structurelle à la compréhension de l’insomnie primaire. Les études d’imagerie fonctionnelle au cours du sommeil appuient la théorie de l’hyperactivation dans l’insomnie. D’autres études fonctionnelles ont révélé des altérations dans le traitement cérébral des processus cognitifs et émotionnels dans l’insomnie primaire. Les résultats des études structurelles suggèrent des modifications neuroanatomiques, particulièrement dans l’hippocampe, le cortex cingulaire antérieur et le cortex orbitofrontal. Cependant, ces résultats ne sont pas concordants d’une étude à l’autre. Quelques études spect...
Neuroimaging insights into the pathophysiology of sleep disorders
2008
Neuroimaging methods can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. However, it is still unclear how these new data might improve our understanding of the pathophysiology underlying adult sleep disorders. Here we review functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). The studies reviewed include neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy), metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging), and ligand marker measurements. Based on the current state of the research, we suggest that brain imaging is a useful approach to assess the structural and functional correlates of sleep impairments as well as better understand the cerebral consequences of various therapeutic approaches. Modern neuroimaging techniques therefore provide a valuable tool to gain insight into possible pathophysiological mechanisms of sleep disorders in adult humans.
DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy
Sleep Medicine, 2012
Background: Symptomatic narcolepsy is often related to hypothalamic, pontine, or mesencephalic lesions. Despite evidence of disturbances of the hypothalamic hypocretin system in patients with idiopathic narcolepsy, neuroimaging in patients with idiopathic narcolepsy revealed conflicting results and there is limited data on possible structural brain changes that might be associated with this disorder. Methods: We investigated with diffusion tensor imaging (DTI) whether microstructural abnormalities in the brain of eight patients with idiopathic narcolepsy with cataplexy are detectable compared to 12 healthy controls using a 1.5 T MRI scanner. Whole-head DTI scans were analyzed without an a priori hypothesis. Voxelwise statistical analysis of fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics (TBSS), a non-linear analysis approach. Results: Patients with narcolepsy showed microstructural white matter changes in the right hypothalamus as well as in the left mesencephalon, pons, and medulla oblongata. Additionally, areas in the left temporal lobe, the pre-and postcentral gyrus, the frontal and parietal white matter, the corona radiata, the right internal capsule, and the caudate nucleus had altered microstructure in patients with narcolepsy. Conclusions: Our study shows widespread microstructural white matter changes that are not visible on conventional MRI scans in patients with idiopathic narcolepsy. In support of the evidence from patients with symptomatic narcolepsy, we found microstructural changes in the hypothalamus, mesencephalon, pons, and medulla oblongata. Changes are in accordance with disturbances of the hypothalamic hypocretin system and its projections to mesencephalic and pontine areas regulating REM sleep.
Altered regional cerebral blood flow in idiopathic hypersomnia
Sleep
Study Objectives: Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Methods: Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99m Tc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Results: Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. Conclusions: These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness.
Seminars in Neurology, 2009
The neurobiology of sleep and narcolepsy is reviewed. Non-rapid eye movement (NREM) sleep is generated by neurons in the preoptic region of the hypothalamus and adjacent basal forebrain. Lesions in these regions cause insomnia. Stimulation of these regions rapidly produces sleep onset. The key brain structure for generating REM sleep is the pons and adjacent portions of the midbrain. Damage to the pons and/or caudal midbrain can cause abnormalities in REM sleep. The persistent sleepiness of narcolepsy is a result of a loss of hypocretin function.