Continuing our series on conditions that GPs might rarely encounter, neurology consultant Dr Clare Bolton provides an overview of narcolepsy
What is narcolepsy?
Narcolepsy is a condition causing patients to experience excessive sleepiness during the day and sleep disruption overnight. Dream sleep (Rapid Eye Movement sleep or REM sleep) phenomena occur at odd times.
There are two types of narcolepsy, Type 1 and Type 2.
In Type 1 there is loss of a hypothalamic neurochemical orexin (also known as hypocretin) which functions to maintain alertness and stabilise wake and sleep states. Patients with Type 1 narcolepsy experience cataplexy, a loss of muscle tone in response to strong positive emotions, in addition to the symptoms mentioned above.
Cataplexy is absent in Type 2 narcolepsy. This is the only difference between the two types. The underlying cause of Type 2 narcolepsy is not known.
A basic knowledge of sleep and wake physiology is helpful to understand the pathophysiology of narcolepsy. With a normal sleep and wake pattern, we remain alert and awake in the day, and then sleep at night. Sleep is structured so that we usually enter non-REM sleep first, with the first period of REM sleep occurring about 90 minutes after sleep onset. We typically have 3 to 4 cycles of non-REM followed by a REM period, while asleep.
During REM sleep, in order to protect us from injuring ourselves while dreaming, the majority of our muscles, apart from the diaphragm and extra-ocular muscles, are ‘paralysed’ by brainstem pathways that inhibit the motor nerves supplying skeletal muscles. Because of the disrupted sleep/wake states, patients with narcolepsy experience REM sleep phenomena at odd times giving unusual symptoms such as sleep paralysis when falling off to sleep or waking from sleep, and hallucinatory experiences at sleep/wake transition periods. Patients often have vivid dreams and can act out dreams while asleep. In Type 1 narcolepsy the normal loss of muscle tone that should occur only during REM sleep happens in response to strong (typically positive) emotions such as when laughing or surprised.
How common is it?
Narcolepsy has an estimated UK incidence of about 1/100,000 per year and a prevalence of 40/100,000 (combining Type 1 and Type 2). The prevalence of Type 1 narcolepsy is estimated between 10-20/100,000. This means that an average GP practice with about 10,000 patients may have 4 patients with narcolepsy on its books. Symptoms typically start in adolescence and early adulthood, but can start any time from pre-school age to late adulthood. Symptoms may be unrecognised for years so that initial presentation can be in later life.
What is it often confused with?
Other conditions causing excessive daytime sleepiness include sleep apnoea syndrome, restless legs syndrome, circadian rhythm problems such as a delayed sleep phase, restricted sleep time and sedating medications such as night-time tricyclic antidepressants. Cataplexy can be mistaken for any other causes of collapse such as syncope, functional disorders and seizures.
Red flags to indicate narcolepsy
The tetrad of features for Type 1 narcolepsy are: excessive sleepiness, sleep paralysis, sleep related hallucinations, and cataplexy. Type 2 is similar but without cataplexy.
Consider narcolepsy in patients who have uncontrolled sleep attacks – sudden onset of sleep with little warning – and in patients who fall asleep in unusual situations such as talking to people, soon after waking, during meals, or patients who have to go to a quiet place while at work to have a nap. Short naps (for 15 minutes or so) are typically refreshing.
Children with narcolepsy may fall asleep in lessons; in particular, falling asleep in morning lessons suggests pathological sleepiness. They may also develop irritability with ‘ADHD’-like symptoms, behavioural or mental health problems due to sleepiness and struggling to maintain alertness. It is important to rule out behavioural causes and poor sleep hygiene. It is the combination of daytime sleepiness and the other features of the ‘tetrad’ that help with the diagnosis and distinguishing narcolepsy from other causes of excessive sleepiness.
Sleep paralysis and vivid dreams are common but usually infrequent in the general population and associated with sleep disruption or sleep restriction. In narcolepsy these symptoms are frequent, and patients often have vivid dreams during short naps (as REM sleep occurs soon after sleep onset). Dream enactment behaviour (also known as REM sleep behavioural disorder) can be seen as a prodrome to Parkinsonian disorders in older patients, but if occurring in young patients with associated daytime sleepiness consider narcolepsy.
Cataplexy is diagnostic of Type 1 narcolepsy. It often initially affects face or neck muscles before descending to affect the rest of the body. Patients may collapse but not suddenly drop or fall. The key is that it is triggered by (usually positive) emotion such as laughing, surprise, the build up to a punchline of a joke, or winning at a game, but can also be triggered by anger. Children with cataplexy often have facial weakness or eyelid ptosis. The tongue lolling out during cataplexy is characteristic in this age group. Precocious puberty and new onset obesity is associated with Type 1 narcolepsy in kids due to hypothalamic dysfunction from loss of orexin.
How can GPs diagnose narcolepsy?
Taking a thorough history of sleep phenomena and daytime symptoms of sleepiness is key. The Epworth Scale can give a measure of daytime sleepiness and is often high in patients with narcolepsy. Consider other sleep disorders and causes of disrupted sleep. Consider screening for sleep apnoea if there is a history of snoring and risk factors, but note that tests for sleep apnoea only assess overnight oxygen levels (oximetry studies) with some also assessing breathing movements (respiratory polygraphy), and do not measure sleep stages or determine other causes of sleep disturbance. Patients need to be informed of DVLA regulations and GPs should advise patients not drive if excessively sleepy while at the wheel whatever the cause of their sleepiness is. Those diagnosed with narcolepsy need to inform the DVLA and legally are not allowed to drive for at least 3 months. Refer to the local sleep service if narcolepsy is a possibility after considering other potential causes of daytime sleepiness.
The diagnosis of narcolepsy is made using an inpatient overnight sleep study (polysomnography) which assesses brainwave activity to determine sleep stages, limb movements, breathing, and can capture any unusual events while asleep on a video. The polysomnography is used to rule out other causes of disrupted sleep, and is followed by a Multiple Sleep Latency Test (MSLT). This objectively assesses the degree of daytime sleepiness by giving patients several opportunities to nap during the day, and determines whether the patient enters REM sleep soon after sleep onset (known as Sleep Onset REM Periods SOREMPs). Falling asleep quickly during nap opportunities with at least two SOREMPs are a diagnostic feature of narcolepsy as long as other causes, such as sleep deprivation, are ruled out. Sometimes a lumbar puncture is performed to measure levels of CSF orexin (which will be low in those with Type 1 narcolepsy) particularly when there is diagnostic uncertainty from the history or non-diagnostic polysomnography/MSLT results.
Treatment and prognosis
Narcolepsy is a lifelong condition that cannot be cured but does not progress with time. Symptoms can usually be well controlled with a combination of non-pharmacological strategies and medications. The former involves good sleep hygiene practices and scheduled daytime naps.
Medications include stimulant drugs to increase daytime alertness such as modafinil, methylphenidate and dexamphetamine. All can cause hypertension, increase heart rate, weight loss, and mood disturbance such as irritability, anxiety or low mood, and so regular checks of these parameters after a dose increase and then every 3-6 months is recommended. Modafinil is teratogenic and an enzyme inducer, reducing the effectiveness of some hormonal contraceptives. It should not be initiated in women of childbearing potential unless they are using a reliable method of contraception such as the copper coil, intrauterine device or depot injection or sterilisation.
Stimulant medications are typically initiated by hospital specialists and once patients are on a stable dose shared care agreements with GPs may be requested. Cataplexy is treated with anti-depressant agents such as venlafaxine, clomipramine or SSRIs all of which reduce REM sleep. Management of co-morbid sleep problems and associated neuro-endocrine features in children is also important.
Dr Clare Bolton is a neurology consultant for the Respiratory Support and Sleep Service at The Royal Papworth Hospital in Cambridge
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Not entirely directly relevant, but the comment about shared care, just made me think back : GPs used to be happy to continue drugs started by consultants in hospital or OPD, and that was how we became familiar with them. We could monitor, and could easily contact Consultant for advice if any problem.
So, why are GPs not happy to start patients on things now ?
Well, for a start, it is the starting something, rather than continuing it;
Then there is the who is asking – not always a Consultant after thorough medical assesment these days, but could be almost anyone at the service who has heard of something, but not necessarily any experience of using it or knowledge of monitoring needs;
Then there is the difficulty in getting access to the familiar consultant whom we trust, to get advice for a problem – which is amost impossible these days;
Then there is the knowing about necessary monitoring, for an ever increasing range of new drugs;
And the being able to do the monitoring, persuade patients to come in, have time to do it, etc;
And then there is the litigious nature of patients these days if something does go wrong;
And the fact that a lot of these things recommended are off-license; not recommended for the problem in hand, third or fourth choices in patients who have not tried the best option yet, and drugs of abuse and/or with side effects.
No, I do not wonder why GPs are reluctant;
I do wonder why anyone ever thought we would welcome this risky role!