The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Functional implications of sleep development. A noradrenergic mechanism functions to couple motor behavior with arousal state. Health-related quality of life effects of modafinil for treatment of narcolepsy. Health-related quality of life in narcolepsy. Age at onset of narcolepsy in two large populations of patients in France and Quebec. Clinical aspects and pathophysiology of narcolepsy. Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives. European Society of Sleep Technology, (2001).ĭauvilliers, Y., Arnulf, I. The international classification of sleep disorders, revised. This Review describes the clinical and pathophysiological aspects of cataplexy, and outlines optimal therapeutic management strategies.Īmerican Academy of Sleep Medicine. Despite major advances in understanding disease mechanisms in cataplexy, therapeutic management is largely symptomatic, with antidepressants and γ-hydroxybutyrate being the most effective treatments. The amygdala and medial prefrontal cortex contain neural pathways through which positive emotions probably trigger cataplectic attacks. Muscle weakness during cataplexy is caused by decreased excitation of noradrenergic neurons and increased inhibition of skeletal motor neurons by γ-aminobutyric acid-releasing or glycinergic neurons. One pathogenetic mechanism that has been hypothesized for cataplexy is the activation, during wakefulness, of brainstem circuitry that normally induces muscle tone suppression in rapid eye movement sleep.
This disorder occurs almost exclusively in patients with depletion of hypothalamic orexin neurons. Occurring spontaneously, cataplexy is typically triggered by strong positive emotions such as laughter and is often underdiagnosed owing to a variable disease course in terms of age of onset, presenting symptoms, triggers, frequency and intensity of attacks. Cataplexy is incapacitating because it leaves the individual awake but temporarily either fully or partially paralyzed. Novel and experimental treatments to manage cataplexy are required, including orexin replacement therapy and immune-based therapiesĬataplexy is the pathognomonic symptom of narcolepsy, and is the sudden uncontrollable onset of skeletal muscle paralysis or weakness during wakefulness. Γ-Hydroxybutyrate (GHB) and antidepressants are effective treatments for cataplexy, but most treatments (excluding GHB) are used 'off-label' Reduced noradrenergic and increased inhibitory input to motor neurons causes muscle weakness or paralysis during cataplexy positive emotions trigger cataplexy through neuronal pathways in the amygdala and medial prefrontal cortex The pathogenesis of cataplexy in human narcolepsy involves degeneration of orexin neurons in the hypothalamus genetically induced orexin deficiency causes cataplexy in both mice and dogsĬataplexy is thought to result from activation during wakefulness of the sleep circuitry involved in rapid eye movement sleep Cataplexy is the pathognomonic symptom of narcolepsy, and is characterized by sudden involuntary loss of skeletal muscle tone during wakefulness, typically triggered by strong positive emotions
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