Causes of narcolepsy
Narcolepsy is a neurological condition associated with a fault in the mechanisms in the brain which control wakefulness and sleep. One of the main characteristics of the condition is the intrusion of rapid eye movement (REM) sleep at inappropriate times. During REM sleep the brain is very active and the muscles of the body relaxed (paralysed). In non narcoleptic people REM sleep does not occur until sleep has been underway for some time. However, in people with narcolepsy REM sleep often occurs soon as they fall asleep on even as they are awake.
For over a hundred years - since the condition was first described - the cause of narcolepsy was unknown. It only since the late 1990’s that huge steps have been made in the understanding of the causes of the condition.
The newly discovered neurotransmitter ('chemical messenger') orexin (also known as hypocretin) is thought to be involved in the control of wakefulness and sleep. The nerves containing this neurotransmitter are found in a part of the brain called the hypothalamus and extend to areas of the brain which control sleep and wakefulness. In 1999 workers in Texas found that mice which could not make orexin in their brains developed the symptoms of narcolepsy, including sleep attacks and cataplexy. At the same time a group in California found that dogs with narcolepsy have a faulty receptor for orexin. After these exciting results scientists throughout the world rushed to see whether there was a problem with orexin in humans with narcolepsy. Sure enough, in 2000 a group from California found that the levels of orexin in the cerebrospinal fluid (CSF - the liquid which bathes the brain and spinal cord) was very low or even undetectable in most patients with narcolepsy. These results have since been confirmed in several studies. Other scientists have found that the brains of narcoleptic patients have very little orexin in them and that the nerves containing orexin have degenerated. It now looks as though narcolepsy may turn out to be a ‘neurodegenerative’ illness such as Parkinson’s disease for example. The cause(s) of the death of the orexin neurones is currently unknown.
The strong association between HLA type and narcolepsy with cataplexy raises the possibility that narcolepsy is an autoimmune disease. However, there is no strong evidence of inflammatory processes or immune abnormalities associated with narcolepsy. Typical biochemical markers found in autoimmune conditions have not been discovered - to date - in narcolepsy.
It should be noted that about 10% of patients with narcolepsy and cataplexy have normal CSF orexin levels. It has been suggested that this sub-group of patients may have faulty orexin receptors rather than faulty orexin production. The exact explanation for this phenomenon is, however, currently uncertain.
A great deal of research is being undertaken on the relationship between orexin and narcolepsy. This website will be updated as and when this research generates information of relevance to the narcoleptic patient.
Recent (2008) information from Japan suggests that narcolepsy is associated with a DNA mutation between two genes known to be involved in sleep control mechanisms.