Download Revision card narcolepsy

SLEEP DISORDERS
EXPLANATIONS FOR NARCOLEPSY AND SLEEP WALKING
THE NATURE OF SLEEP
LIFESPAN CHANGES IN SLEEP
KEYAND
TOPICS
KEY CONCEPTS
Cataplexy
somnambulism
Hypocretins
HLA gene
KEY STUDIES
Lin et al
l
Narcolepsy is a disorder marked by excessive daytime sleepiness, uncontrollable sleep attacks, and cataplexy (a
sudden loss of muscle tone, usually lasting up to half an hour). Two main symptoms are feeling sleepy al the time and
episodes of cataplexy. Cataplexy is sudden and transient episode of loss of muscle tone, often triggered by emotions.
It is a rare disease (prevalence of fewer than 5 per 10,000 in the community), but frequently affects people who have
narcolepsy, a disorder whose principal signs are EDS (excessive daytime sleepiness), sleep attacks, sleep paralysis,
hypnagogic hallucinations and disturbed night-time sleep. Such episodes seem to be triggered by various forms of
emotional arousal, such as, fear, amusement, or stress.
There have been a variety of explanations that have been put forward. In the 1960’s the view was that it was linked
to a malfunction in the system that regulates REM sleep, which explained some of the symptoms of narcolepsy,
including, cataplexy which accompanies REM sleep. More recently, research uncovered a link between the
neurotransmitter hypocretin (orexin) in the cerebrospinal fluid and narcolepsy. Hypocretins appear to play an
important role in maintaining wakefulness. Lin et el (1999) found this in narcoleptic dogs. In relation to cataplexy, it is
known that various neurons in the medulla that are normally active during REM sleep, become active when a collapse
occurs. These neurons normally send messages to the spinal cord to suppress skeletal muscle movements during REM
sleep; hence they are inappropriately active during normal waking hours.
Somnambulism occurs when an individual leaves their bed and walks around as if awake. Most episodes are short,
varying from seconds to minutes. Episodes typically occur during SWS Stages 3 and 4 and tend to happen during the
first half of the night.
Sleepwalking in an individual is 10 times more likely if a first degree relative has had a history of sleepwalking. Hence it
has been concluded that sleepwalking can be inherited. Bassati (2002) studied 74 patients who were diagnosed with
adult sleepwalking and found that, of the 16 patients who underwent genetic testing, 50% of them had a specific gene
that was present in only 24% of healthy people. The gene is one of a family of genes producing HLA proteins, which
are involved in regulating the immune system. It is the same genetic variant of the HLA gene associated with
narcolepsy.
A number of strains of dogs exhibit
narcolepsy, where following
excitement (such as the appearance of
food or another dog) they suddenly
keel over and pass directly into REM
sleep.
The same drugs that are used to treat
the cataplexy part of narcolepsy in
humans also work to suppress this
condition in dogs. A mutant gene was
identified in these animals, which was
found to affect a receptor (the area on
the surface of a neuron where
neurotransmitters can cause the
neuron to fire). This gene affects
specialized cells called hypocretin
neurons.
It has been found that humans with
narcolepsy have lost around 90% of
their hypocretin neurons. Such
neurons are found in the
hypothalamus in both dogs and
humans.
COMMENTARY
SYNOPTIC LINKS
D
Biological approach
One problem with research into
measures involving the
measurement of spinal fluid levels
in humans is that people are fairly
reluctant to volunteer for such
research. Through selective
breeding and genetic analysis there
are now a number of dogs used in
the research. Questions exist as to
the generalisability of non-human
animal research of this type. Many
would argue that important
findings have been discovered from
animal research, others claim that
there is a qualitative difference
between humans and other
animals. For example, the inherited
nature of narcolepsy has been
shown to be qualitatively different
in humans compared to dogs.
Nevertheless, it is difficult to deny
the value of much of this animal
research in respect to humans.
Whether humans should use
animals in this way for the benefit
of humans, remains open to
question. It has been claimed that
using animals in this way is an
example of ‘speciesism’.
The narcolepsy-HLA link continues to be researched, though the specific HLA variant
found most commonly in narcoleptics is not found in all narcoleptics and is also
reasonably common in the general population. This means HLA cannot be the sole
explanation.
SYNOPTIC LINKS
Nature-Nurture
SYNOPTIC LINKS
Hypocretins are the most promising lead. The findings from narcoleptic dogs have been
confirmed in human studies. For example, it was found that human narcoleptics had lower
levels of hypocretin in their cerebrospinal fluid. However, low levels of hypocretin are
unlikely to be due to inherited factors because human narcolepsy doesn’t run in families
and it has not been found to be concurrent in twins where one has the disorder. The
reduction in hypocretin may be due to brain injury, infection, diet or stress, or is possibly
the result of an auto-immune attack. This could explain the HLA link with narcolepsy
because of the role of HLA in the immune response.
Bassetti’s study was the first study to demonstrate a familial relationship in adult
sleepwalking (SW)and it was also the first time that a specific genetic marker for adult SW
had been found. However, it remains unclear what the exact nature of the relationship
between the HLA gene and SW is. Although sleepwalkers appear to have an increased
frequency of the HLA gene, it doesn’t mean that the gene is entirely responsible for the
sleepwalking disorder. It may be that some other genes close by, that happen to be
transmitted together through generations are involved. A further problem is that not all
sleepwalkers were identified as having the gene and some 25% of the control group who
were not sleepwalkers did have the gene. Nevertheless it does appear that the gene may be
implicated in some way with SW.
SW fits neatly into the diathesis-stress model. The diathesis comes from a genetic
predisposition to the disorder. A concordance rate of 50% has been found in MZ’s compared
to 10% in DZ’s. the stress part of the model is represented either by maturity in certain key
neural circuits in the brain or by the amount of SWS. Other risk factors e.g. sleep
deprivation, alcohol and fever, all increase SWS and this may trigger SW.
D
M
An additional problem
with Bassetti’s study is
that the sample of
sleepwalkers studied
were not necessarily
representative of the
general population of
sleepwalkers. Most
sleepwalkers do not seek
help or come to the
notice of sleep
researchers since they
are either not aware of
their problem or they
don’t find it causes them
too many problems.
Sleepwalkers who do not
seek help are most
frequently those who
have injured themselves
while sleepwalking. This
group of sleepwalkers
may be qualitatively
different to the rest of
the sleepwalking
population.