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Cataplexy—clinical aspects, pathophysiology and management strategy

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

Abstract

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.

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Figure 1: Video-polysomnographic recording of a patient during a cataplectic attack with loss of muscle tone.
Figure 2: Hypothetical circuits and pathways controlling cataplexy in the rodent brain.

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Y.D. researched data for the article. Y.D., J.M.S. and J.H.P. wrote the article and substantially contributed to discussion of the content. Y.D., J.M.S., R.L., Z.A.T. and J.H.P. reviewed and/or edited the manuscript before submission.

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Correspondence to Yves Dauvilliers.

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Y.D. declares that he has received speaker honoraria and support for travel to meetings and has participated on the advisory boards for the following companies: UCB Pharma, JAZZ and Bioprojet. The other authors declare no competing interests.

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Narcoleptic human

A prolonged cataplexy rebound after 10 day withdrawal of clomipramine, venlafaxine and methylphenidate in a man aged 29 years affected with narcolepsy–cataplexy for 2 years. The patient remained fully conscious and was able to interact, respond and remember what happened during the cataplectic episode. Written consent for publication was obtained from the patient. (AVI 8955 kb)

Narcoleptic mouse

An Hcrt−/− mouse showing normal grooming behaviour, which is interrupted by a short but typical cataplectic attack that ends in the mouse resuming normal waking activity. (AVI 2658 kb)

Narcoleptic dogs

Three littermate, 4 month-old narcoleptic Doberman Pinschers show partial and complete cataplectic attacks triggered by eating meat. (MOV 6247 kb)

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Dauvilliers, Y., Siegel, J., Lopez, R. et al. Cataplexy—clinical aspects, pathophysiology and management strategy. Nat Rev Neurol 10, 386–395 (2014). https://doi.org/10.1038/nrneurol.2014.97

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