Journal Article

Cataplexy—clinical aspects, pathophysiology and management strategy

Dauvilliers, Yves, Peever, John H., Siegel, Jerry M., Torontali, Zoltan A., Lopez, Regis

2014

Overview

Key Points 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 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 dogs Cataplexy is thought to result from activation during wakefulness of the sleep circuitry involved in rapid eye movement sleep 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 γ-Hydroxybutyrate (GHB) and antidepressants are effective treatments for cataplexy, but most treatments (excluding GHB) are used 'off-label' Novel and experimental treatments to manage cataplexy are required, including orexin replacement therapy and immune-based therapies Cataplexy is the pathognomonic symptom of narcolepsy, a condition that is caused by depletion of orexin neurons. Cataplectic attacks are characterized by sudden involuntary muscle weakness or paralysis, often triggered by strong emotions. In this article, Dauvilliers et al . review the latest understanding of potential mechanisms underlying narcolepsy and cataplexy, the utility of experimental models, and the need for early diagnosis and therapy. Cataplexy is the pathognomonic symptom of narcolepsy, and is the sudden uncontrollable onset of skeletal muscle paralysis or weakness during wakefulness. Cataplexy is incapacitating because it leaves the individual awake but temporarily either fully or partially paralyzed. 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. This disorder occurs almost exclusively in patients with depletion of hypothalamic orexin 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. 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. The amygdala and medial prefrontal cortex contain neural pathways through which positive emotions probably trigger cataplectic attacks. Despite major advances in understanding disease mechanisms in cataplexy, therapeutic management is largely symptomatic, with antidepressants and γ-hydroxybutyrate being the most effective treatments. This Review describes the clinical and pathophysiological aspects of cataplexy, and outlines optimal therapeutic management strategies.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/699/375/1816 / 692/700/565 / Animals / Antidepressants / Brain - pathology / Care and treatment / Cataplexy / Cataplexy - diagnosis / Cataplexy - physiopathology / Cataplexy - therapy / Electroencephalography / Emotions / Eye movements / Health aspects / Humans / Medical case management / Medicine & Public Health / Methods / Mood Disorders - etiology / Muscle Weakness - etiology / Musculoskeletal system / Nerve Degeneration - etiology / Neurology / Neurosciences / Ocular Motility Disorders - etiology / Pathophysiology / Quality of life / review-article / Sleep disorders