ResearchBlogging.orgEveryone knows what narcolepsy looks like from movies like the ridiculous display in Deuce Bigalow (one of the ‘adorable misfit bunch of suitors’) to other more subdued examples like Mike in My Own Private Idaho. Oh, and when I say that, I mean people know the stereotype of the instantaneous drop during dinner into a bowl of soup. What I really mean is that the stereotype isn’t the norm at all.

Young Couple Sleeping

A rare narcoleptic couple in the wild. Credit: epSos.de

Furthermore narcolepsy is often confused with cataplexy, a related yet very distinct condition. So what’s the difference and what’s the deal with narcolepsy?

Narcolepsy is characterised by four basic symptoms known as the ‘tetrad of narcolepsy’, cataplexy, sleep paralysis, hypnagogic hallucinations (hallucinations associated with the transition between asleep and awake) and excessive daytime sleepiness (EDS).

Cataplexy is simply one of the characteristics of narcolepsy and refers to a sudden onset muscle weakness, which can be experienced alongside or independently from narcolepsy. Cataplexy, like narcolepsy, has varying degrees of severity. Some only suffer from weakness in facial muscles that fades quickly but in severe cases the weakness can be felt in all skeletal muscles at the same time causing the sufferer to drop (if you'll mind the use of the word) into a paralysed state while remaining entirely conscious of their surroundings and what is happening to them. For sufferers this condition is understandably terrifying.

Another of the defining characteristics of narcolepsy is that its sufferers seem to have the ability to enter deep rapid eye movement (REM) sleep in as little as 10 min. Most people take approximately 90 min to achieve this level of sleep and this is a really significant part of the problem. Essentially this, alongside all the other symptoms suggests the brain does not follow the normal pattern of sleep. REM sleep is when dreaming occurs which explains the hypnagogic hallucination as there is no non-REM (NREM) sleep to buffer dreaming from wakefulness (hypnagogic means sleep leading and refers to the transition sleep to awake and vice versa). The cataplexy and sleep paralysis reflect the encroachment of REM atonia into wakefulness resulting in muscle paralysis when it is not desired.

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I don't think my dogs are narcoleptic, just lazy. Credit: me.

Both narcolepsy and cataplexy can appear at the same time as both have similar triggers, most notably strong emotional reactions, which can set them off together. Despite the neurological trigger it is predicted that both conditions share a level of genetic involvement as well as both conditions have been shown to run in families.

An interesting discovery in narcolepsy research is the involvement of a region of DNA on chromosome 6 involved in the production of human leukocyte antigen (HLA, a.k.a Major Histocompatability Complex or MHC in mice). I won't go into it here but the HLA is related to antibodies, which the body uses to identify things that shouldn’t be in the body and target them for removal. Some, not all, narcoleptics show a number of important variations in their HLA’s that increase their ability to target orexin-producing neurons in the brain. What is orexin? Orexin is a fundamental controller of both appetite and sleep-patterning suggesting that some forms of narcolepsy are in fact an autoimmune disease!

Treating such an unusual disease necessarily takes an individual by individual response but certain guidelines are followed. Initially central nervous system (CNS) stimulants are given. Amphetamine based drugs were favoured but new drugs like Modafinil and Armodafinil are now used instead. Exactly how these drugs work is not known but what we do know is they work differently to amphetamines and some attributes are shared, such as the effects of the drugs on dopamine levels in the brain. For this reason both –dafinals are monitored for potential abuse and addiction.

Other drugs which are less effective stimulants but have lower abuse potentials include atomoxetine which inhibits the reuptake of noradrenalin allowing it to persist allowing its effects such as increasing heart rate, promotion of glucose release from the muscles and increasing blood flow to the brain to persist.

Cataplexy on the other hand needs its own special attention. Commonly Xyrem is prescribed as its activity reduces EDS and improves the quality of night time sleep and may be involved in assisting the repair on the brain during sleep when it is least active.

It has also been shown that drugs that inhibit REM sleep or stimulate greatly during the day can be useful but often induce sleep disturbance and over time may actually make the condition worse.

The best treatment options are all lifestyle changes. Short but planned naps throughout the day seem to be very effective, as is an improved diet, exercise, dropping stressful activity and of course the reduction of non-essential stimulants (coffee, nicotine).

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What do you mean I can't have coffee??!?!?!??!?!? Credit: solylunafamilia

Narcolepsy and the associated symptoms like catalepsy are devastating for the sufferer’s attempts at living a normal life, but it is possible. Drugs are making it easier to handle the seizures and many are able to keep their condition under wraps if they want to. This complex condition involves interruption of diurnal rhythms, interrupted sleep patterning and all the physiological upheaval that brings but with the identification of a cause comes the prospect of a cure and the potential to treat narcolepsy as an auto-immune disease is very encouraging for all involved.

References

Klein J, & Sato A (2000). The HLA system. Second of two parts. The New England journal of medicine, 343 (11), 782-6 PMID: 10984567

Mignot E (2001). A commentary on the neurobiology of the hypocretin/orexin system. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 25 (5 Suppl) PMID: 11682267

Maret S, & Tafti M (2005). Genetics of narcolepsy and other major sleep disorders. Swiss medical weekly, 135 (45-46), 662-5 PMID: 16453205

Zorick FJ, Salis PJ, Roth T, & Kramer M (1979). Narcolepsy and automatic behavior: a case report. The Journal of clinical psychiatry, 40 (4), 194-7 PMID: 422531