Narcolepsy 

Is a disorder of the sleep-wake cycle which results in excessive sleepiness and often a loss of muscle tone resulting in cataplexy.  About 1 in 2,000 people suffer from the disorder and worldwide it is estimated that there are 3 million sufferers.  Until very recently the cause was unknown but major advances have been made in the past 10 years that are now giving hope that a successful treatment can soon be found.

Symptoms

Excessive daytime sleepiness (EDS) is usually the first symptom to present itself.  Initially patients try very hard to stay awake but find that if they do this then they are faced with involuntary attacks of sleep that can strike at any time.  Periods of micro-sleep resulting in brief naps lasting less than 30 seconds are also common.  Very often the patient themselves are unaware of these though observers find them disconcerting. 

EDS can cause knock on effects with memory loss, focusing of eyes and tiredness.  Often friends initially find these first symptoms signs of rudeness, laziness or lack of interest. 

Cataplexy (muscle paralysis) is the other major symptom, although 25% of narcoleptics never seem to experience this.  Until recently it had been argued that cataplexy was an essential symptom of the disorder but recently it was decided that the disorder could be diagnosed even in those that never suffer from it. 

The paralysis may only affect the muscles of the face but in more severe cases can result in loss of all muscle tone causing the patient to collapse on the floor.  Although the paralysis usually lasts a matter of minutes, repeated attacks can result in the patient being immobilized for up to half an hour, particularly if the trigger, such as excitement persists. 

Very often cataplexy doesn’t develop or many years following the initial first signs of narcolepsy (usually EDS) which makes an early diagnosis of the disorder unlikely.  It is usual for narcoleptics not to be diagnosed until 12 to 15 years following the first symptoms!

Other symptoms

Although the patient may sleep for many hours a day, night time sleep is constantly interrupted by waking, increased heart rate, periods of alertness and hot flushes.

The day time attacks of cataplexy are often accompanied by vivid hallucinations which seem to be due to REM sleep encroaching on wakefulness.  The patient is still fully conscious and aware of what is going on around them so such hallucinations can be frightening and difficult to distinguish from reality.  Similar to this are the very vivid hypnogogic and hypnopompic hallucinations that we often experience on falling asleep and just prior to waking up respectively. 

Automatic behaviours are also experienced.  The patient behaves as if on autopilot, carrying out every day behaviours, often unaware, and often getting them wrong, for example pouring milk into the teapot. 

Early REM: as we’ve already seen, our first bout of REM sleep usually occurs after 60 or 70 minutes of NREM or slow wave sleep, before reoccurring every 90 minutes or so (the ultradian rhythm).  Narcoleptics often nod off straight into REM sleep at the start of the night. 

Age of onset

First signs of the disorder (EDS) usually occur between 15 and 30 years of age, but can be as young as five.  As already mentioned, it may take many years for the full symptoms to appear and for a correct diagnosis to be made.  

Causes

Narcolepsy is NOT a psychological disorder but a neurological condition resulting in a fault in the mechanisms controlling the normal, circadian, sleep-wake cycle resulting in REM sleep occurring at inappropriate times. 

Research on dogs by Mignot and others has suggested a genetic link with the disorder.  Dr Emmanuel Mignot has bred a colony of narcoleptic dogs (Labradors and Dobermans ) at his laboratory Stanford University.  However, the disorder doesn’t appear to be so clearly defined in humans with what appears to be a lesser genetic component. 

In recent years the neurotransmitter hypocretin (sometimes referred to as orexin) has been implicated in the disorder. In the late 1990s Dr Yanagisawa was testing hypocretin’s use as an appetite suppressant on rats.  He bred mice that couldn’t produce hypocretin and found that they ate far less than normal.  However, he noticed that over time they actually put on weight rather than lost it as would be expected.  When he taped their behaviour he found that instead of being very active at night they were having frequent attacks o cataplexy, as had been observed in narcoleptics. 

Work by Mignot on his dogs isolated a fault on the hypocretin-2-gene that produces hypocretin which seemed to support the earlier work.   

Siegel et al (2000) managed to acquire the preserved brains of 4 narcoleptics and after a close examination they were found to have 93% fewer hypocretin neurons than a non-narcoleptic’s brain.  This was subsequently supported by Mignot. 

More recently low levels of hypocretin have been found in the CSF of humans with the disorder.

Further research is still ongoing.  It has been found that small injections of hypocretin can reduce the cataplexy in dogs, however larger injections make the cataplexy work.  This seems to be due to different areas of the midbrain responding in different ways to the chemical.  The locus coerulus (already mentioned in the physiology of sleep) seems to be crucial in the whole process. 

Hypocretin certainly plays an important role in keeping us awake.  During the day it acts on the locus coerulus o keep us awake, at night time production of the chemical by the hypothalamus stops so we can nod off.

Evaluation of narcolepsy research

The drug modafinil has been used an effective treatment for some cases of narcolepsy.  It is thought that modafinil stimulates production of hypocretin by the hypothalamus. 

As we’ve already seen, injections of hypocretin can reduce the cataplexy experienced by narcoleptic dogs. 

There is clearly a genetic component to narcolepsy but as shown in dogs and with a limited tendency for the disorder to run in human families.  However, the research by Mignot on dogs does suggest that there are serious issues of generalisation between the two species.  In dogs one group of genes (the so called HLA complex on chromosome 11) appears to be responsible for narcolepsy. 

In humans, however there is a high level of discordance in MZ twins.  If one twin as narcolepsy there is only a 30% chance that the other will develop the disorder. 

Although levels of hypocretin is a  major contributory factor, further clarification of its precise role is needed.  Mahowald and Schenck (2005) report that ‘the absence of hypocretin is neither necessary nor sufficient to explain all the cases of narcolepsy [in humans].
 

Sleep walking (somnambulism)

Sleep walking is a surprisingly common condition with an estimated 10% of the population experiencing it in some form at one time or another in their lifetime.  (note: some texts put the estimate as high as 20%).  One thing is clear, it is far more common in children.  Only about 3% of adults experience sleep walking. 

The Hollywood, cartoon depiction of sleep walkers with arms out in front walking like a robot is far from the mark.  Sleep-walkers move quite naturally and other than the glazed expression in the eyes may appear to be awake.  There are annual reports of people driving cars and even riding horses whilst asleep. 

Somnambulism is associated with deep sleep (not REM obviously) and also night terrors.  Because of its link with stages 3 and 4 of sleep it is more common in the first half of the night and in severe cases there can be more than on episode per night.  Usually sleep-walkers have no recollection of the event when they wake up the next morning. 

Causes

Incomplete arousal

There appears to be an issue of arousal.  EEG monitoring of sleepwalkers shows that typically they have delta activity (a characteristic of deep sleep) with beta activity (characteristic of being awake) mixed in.  Researchers believe that sleepwalking occurs when the patient wakes from deep sleep but the arousal is incomplete so as a result they are not fully woken.  There appears to be a genetic component to this.

Genetic

Sleepwalking certainly appears to run in families (Horne 1992) which in itself may suggest a genetic component.  Hublin et al (1997) in a study of Finnish twins reported that there is a concordance of 66% for boys and 57% for girls.  Again these are high figures suggesting a genetic component. 

Recent genetic evidence

Bassetti (2002) claims to have isolated a specific gene that may be a risk factor in sleepwalking.  HLA DQBI*05 (the gene, not a random string of characters) was found to be present in about 50% of sleepwalkers he tested.  The same gene was only present in about 25% of non-sleepwalkers.  The gene is part of a group of genes involved in the production of the protein HLA and has also been implicated in some cases of narcolepsy.

However, the sample size used was very small.  Out of 74 patients studies only 16 underwent genetic testing and 8 of these were found to have the gene.  The researchers asked for volunteers.  As you should know from AS research methods, this sort of self-selecting sample is the worst possible way of getting participants.  Most sleepwalkers do not seek medical attention or are not even aware of their condition.  Those that do are usually the more serious cases and often include those who have sustained injuries or caused a nuisance.  As a result, they are not a typical cross-section of the sleepwalking fraternity. A neuro-chemical explanation: Antonio Oliviero (writing for Scientific American 2008)

“During normal sleep the chemical messenger gamma-aminobutyric acid (GABA) acts as an inhibitor that stifles the activity of the brain’s motor system.  In children the neurons that release this neurotransmitter are still developing and have not yet fully established a network of connections to keep motor activity under control.  As a result, many [kids] have insufficient amounts of GABA, leaving their motor neurons capable of commanding the body to move even during sleep.”

Olivero goes on to explain that in some this inability to produce sufficient GABA may persist into adulthood.

Olivero also offers a simpler explanation for why sleepwalking is more common in childhood.  Sleepwalking is associated with stage 4 sleep and as we’ve already seen children spend much longer in this stage, which gradually decreases as we get older and completely disappears in the elderly. 

Other factors

Sleepwalking is more common when people are sleep deprived and tired.  Sleepwalking is closely related to restless leg syndrome (RLS) which is a risk factor for insomnia and as a result excessive tiredness. 

RLS is a genetic condition.  This may help explain the genetic component of sleepwalking

Tiredness, sleep deprivation and sleepwalking

Although there are clearly biological predispositions for somnambulism an important trigger appears to be tiredness.

Zadra et al (2008) tested 40 sleepwalking volunteers under laboratory conditions. 

Night one: designed to measure baseline sleep habits.  The participants were observed sleeping in the laboratory

Night two: participants were kept awake.  In fact they went without sleep for 25 hours

Night three: recovery sleep was allowed, with participants being observed again as they slept.

Findings

On the first night, the 40 participants had a total of 32 sleepwalking episodes between them

On the third night (participants sleep deprived) this rose to 92 sleepwalking episodes

This seems to suggest that tiredness can trigger sleepwalking

However, the sample size is relatively small and the first night, used as a control for comparison purposes would have been the first night in the sleep lab.  Perhaps participants were getting used to the new environment. 

The greatest danger to sleepwalkers is self-harm.  It is very rare for them to harm or attack others. 

* does psychiatric mean guessing right three times in a row?

Finished :-)