Canis ISSN: 2398-2942

Narcolepsy

Contributor(s): Seiji Nishino, Simon Platt, Masami Tonokura

Introduction

  • Chronic sleep disorder that affects dogs and humans.
  • Relatively rare; prevalence in dogs not known (human narcolepsy affects 0.02 to 0.18% of general population).
  • Human narcolepsy characterized by excessive daytime sleepiness, cataplexy (ie emotionally-elicited sudden loss of muscle tone that often leads to collapse) and other rapid eye movement (REM) sleep-related abnormalities (hypnagogic hallucinations and sleep paralysis).
  • In narcoleptic dogs most obvious symptom is cataplexy. Abnormal sleep tendency, not apparent.
  • In humans, laughing or anger often triggers cataplexy, while in dogs most typically elicited by presentation of food or by play. Dogs usually remain conscious during cataplexy, but cataplexy can be followed by sleep (unconsciousness), especially REM sleep.
  • Both familial (autosomal recessive) and sporadic cases observed.
  • Pathophysiology: abnormal transition to slow wave sleep and REM sleep, due to impaired hypocretin/orexin neurotransmission. Mutations in hypocretin receptor 2 in familial cases and loss of hypocretin/orexin peptides in sporadic cases.
  • Diagnosis: existence of cataplexy. Cataplexy is sudden onset of weakening of muscle tonus most typically elicited by emotional excitations. Attacks are often described as collapses, buckling of legs, drooping of neck, motionless immobility. Cataplexy needs to be differentiated from similar clinical signs eg epileptic seizures and syncope. No salivation, incontinence, spasm, cyanosis or dyspnea during cataplexy. Measurement of cerebrospinal fluid (CSF) hypocretin-1 levels useful for positive diagnosis in sporadic cases.
  • Treatment: anti-cataplectic medication.
  • Prognosis: neither progressive nor life threatening, but clinical signs persist throughout life. Narcoleptic dogs can be kept as pets with proper treatment and understanding of disease. If clinical symptoms are not manageable and quality of life is severely affected, owner may decide on euthanasia.

Pathogenesis

Etiology

  • Deficiency in hypocretin/orexin neurotransmission, either by loss of hypocretin ligands or function of hypocretin receptor 2.

Predisposing factors

General

  • Familial cases: mutations in one of hypocretin/orexin receptors, hypocretin receptor 2 genes. Mutation is an autosomal recessive with full penetrance, ie both parents must have mutation for offspring to be affected. 100% of puppies born to two affected individuals will be narcoleptic, while approximately 25% of puppies born to parents who are carriers (only one copy of the mutation) will be affected. A dog must have two copies of the mutation in order to be affected and carriers are phenotypically normal (no symptoms).
  • Sporadic cases: unknown.

Pathophysiology

  • Familial cases: mutations in hypocretin receptor 2.
  • Sporadic cases: hypocretin peptide deficiency in CSF and brain.
  • Hypocretins are hypothalamic specific neuropeptides involved in various hypothalamic functions, such as:
    • Sleep.
    • Feeding.
    • Energy homeostasis.
    • Neuroendocrine function.
    • Autonomic nerve function.
  • Deficiency in hypocretin neurotransmission causes monoaminergic/cholinergic imbalance. This is likely to cause sleep abnormality and induction of cataplexy.
  • Hypersensitive to monoaminergic inactivation.
  • Hypersensitive to cholinergic stimulation.
  • Dysfunction in maintenance of, and transition between, vigilance states (difficulty of staying awake and sleep fragmentation).

Timecourse

  • Clinical signs persist throughout life.
  • Symptoms unlikely to worsen with age.

Diagnosis

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Treatment

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Prevention

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Outcomes

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Tonokura M, Fujita K & Nishino S (2007) Review of pathophysiology and clinical management of narcolepsy in dogs. Vet Rec 161 (11), 375-380 PubMed.
  • Tonokura M, Fujita K, Morozumi M, Yoshida Y, Kanbayashi T & Nishino S (2003) Narcolepsy in a hypocretin/orexin-deficient chihuahua. Vet Rec 152 (25), 776-779 PubMed.
  • Ripley B, Fujiki N, Okura M, Mignot E & Nishino S (2001) Hypocretin levels in sporadic and familial cases of canine narcolepsy. Neurobiol Dis 8 (3), 525-534 PubMed.
  • Nishino S, Riehl J, Hong J, Kwan M, Reid M & Mignot E (2000) Is narcolepsy a REM sleep disorder? Analysis of sleep abnormalities in narcoleptic Dobermans. Neurosci Res 38 (4), 437-446 PubMed.
  • Nishino S & Mignot E (1997) Pharmacological aspects of human and canine narcolepsy. Prog Neurobiol 52 (1), 27-78 PubMed.


ADDED