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Narcolepsy
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.
Presenting signs
- Cataplexy, sudden attacks of profound muscle weakness in response to emotional stimulation (feeding, playing etc). Similar to atonia during REM sleep, but occurs suddenly during activity.
Acute presentation
- Before presention with typical cataplectic attacks (complete collapse), dog may present with partial attacks (ie muscle weakness of part of body, neck or legs) or immobility.
Geographic incidence
- Worldwide.
Age predisposition
- Onset in familial cases: 4 - 24 weeks.
- Onset in sporadic cases: varied; later than that of familial cases: 7 weeks - 7 years.
- Clinical signs persist for whole of affected dog's life.
Breed/Species predisposition
- Familial forms (mutations in hypocretin receptor 2) reported in 3 breeds:
- Doberman Pinscher Dobermann.
- Labrador Retriever Retriever: Labrador.
- Dachshund Dachshund.
- Sporadic forms reported in many other breeds (18), including:
- Miniature poodle Poodle: miniature.
- Beagle Beagle.
- Saint Bernard St Bernard.
- Chihuahua Chihuahua - Long Coat Chihuahua - Smooth Coat.
- Mixed breed.
Cost considerations
- Long-term anti-cataplectic medication is disabling.
- Costly to rule out other disorders; may require:
- MRI scan Magnetic resonance imaging: basic principles.
- CSF taps Cerebrospinal fluid: sampling.
- Cardiovascular diagnostics.
Special risks
- Cataplexy itself is harmless (similar to normal REM sleep) and does not lead to death.
- No depression of cardiopulmonary function during attacks.
- Alpha 2 agonists (eg xylazine Xylazine ) may trigger cataplectic attacks. Other anesthetics safe to use with no reported abnormal sensitivity.
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
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Treatment
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Prevention
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Outcomes
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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.