Abstract
Diagnosing sleep disorders requires a slight shift of focus to the dark side, the patients are by definition unreliable narrators – the whole point of sleep is that we are not really there when it happens. However, for the sleep clinic all you need is a short question list, often helped by the bed partner present and a very small number of tests. Sleep disorders are rewarding to treat and this article covers the basics for the jobbing neurologist.
“We see only what we know”
Goethe
Neurologists are trained to spot patterns, we live in a daytime world and the natural tendency is to force every symptom a patient gives you into a daytime diagnosis you are good at spotting. This is one reason sleep disor-ders are missed in the neurology clinic. Labels of “MS fatigue” rather than obstructive sleep apnoea and “absence seizures” rather than micro sleeps on sedative drugs are incorrectly applied. Patients are part of the problem, by definition you are an unreliable narrator when you are asleep and many of the sleep disorders are chronic and slowly worsen over time in people who otherwise look well. The average delay to diagnosis for narcolepsy is 7 years even in recent case series. This is a shame as sleep disorders have highly effective, often life transforming treatment, it is worth learning to recognise them.
A short list of questions can help (Table 1) for anyone who complains of poor sleep with either daytime sleepiness, insomnia, or things going bump in the night (parasomnia). This does not include those who fall asleep without delay, awake refreshed and can share a bed with someone without any protest from their bed partner. People who thought they were fine until they bought a fitbit that told them they got no deep sleep simply need to take off their fitbit at night and keep it for their 10,000 steps a day. Recent validation studies of smartphone apps and wrist worn lifestyle accelerometers emphasise that they don’t provide accurate sleep stage detection but can worsen insomnia. They also bring high intensity light and daytime life into the bedroom.
Two different male patients attending the Sleep Clinic in Newcastle both told a near identical story. An insidious, progressive story over some years of violent dream enactment behaviours caused by failure of the inhibitory pontine signal to spinal motoneurones that normally renders us atonic during our dreams. Both men were married and in their mid 50s with injury to wives as the reason for referral. This is typical REM sleep behaviour disorder, first described in just 5 patients (4 of whom were male) by Carlos Schenck in 1986.
Large case series over the last 30 years have highlighted this as a common parasomnia in 1.0 % of older men with at least 70% injuring them-selves or their bed partners. However, there is a differential including significant sleep apnoea (look for significant daytime sleepiness and snore), and certain antidepressant medications. Ideally an in-patient video sleep study should be used to confirm the diagnosis. As a minimum, a respiratory sleep study can exclude OSA. Without any large RCTs to guide therapy, melatonin (dose range 2-10mg) or second line clonazepam (0.5mg to 2mg) is effective in 70-85% of patients and decreases injury. RBD is now well-recognised as a prodromal symptom for subsequent neuro-degeneration and in particular alpha synuclein-opathies. A recent longitudinal study looking at 1242 patients from 24 different sleep services showed a conversion rate of 7% a year and a 73% chance of conversion by 12 years. Careful population screening shows men and women are equally affected but men present (or are recognised) far more in sleep clinics.
NREM parasomnia includes sleepwalking, night terrors and confusional arousals and unlike RBD, have a younger age of onset, wax and wane over time with limited recall. Events are variable and many will only present after injury or with new partner (or new baby) in the house. Treating daytime anxieties, keeping sleep time fixed and stable and time can be the best therapies. Many simply need reassurance but Table 2 below summarises key difference between NREM, REM and nocturnal seizure.
Younger and very sleepy people may well have narcolepsy – the typical age of onset is 14 with a smaller group presenting later in their mid 30s. The classical tetrad is daytime sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis creating a disturbingly dream filled night. This is still often missed in clinic as symptoms evolve over weeks and months. Sleep attacks are rare and not specific to narcolepsy. A fragmented night is one additional important clue, long deep sleep is unusual in narcolepsy. Power naps are often effective and part of treatment. Cataplexy just looks odd if you haven’t seen it before and it is worth looking at the published teaching videos and asking for home videos. Misdiagnosis as dissociative events can happen if the emotional trigger is missed. Children in particular can have pseudomyopathic faces and near permanent tongue loll and clumsiness.
Narcolepsy in humans is autoimmune with selective degeneration of hypocretinergic hypothalamic neurones. This allows a definitive measurement of cerebrospinal fluid (CSF) hypocretin levels and undetectable levels below 110pg/ml are now sufficient for diagnosis. If there is difficulty accessing polysomnography and multiple sleep latency tests, CSF hypocretin provides a useful alternative.
Education around the condition remains key for the patient. Stimulants decrease sleepiness and improve daytime function with modafinil (100-400mg a day) remaining first line and the only licensed therapy within the BNF. It has a relatively long half life, good safety profile and low risk of dependence or habituation although blood pressure needs monitoring. Venlafaxine is first line cataplexy therapy despite lack of RCT data, the short half life may require either modified release preparations or tds dosing, patients should not stop abruptly or symptoms rebound. Methyphenidate is second line in adults but used more in children. Sodium oxybate has limited access for adults but provision for post pubertal children with NHS England funding. Pitolisant as a novel histaminergic inverse agonist is now available within secondary care in the UK as a long acting, well tolerated stimulant.
Restless legs syndrome was first described as a “snapping of the tendons” by Willis but eloquently characterised in detail by Ekbom in 1944. The associated and strikingly periodic limb movements of sleep were described in 1967 and are seen in at least 80% of patients in the sleep lab. There is no other “mind the gap” movement disorder. The diagnosis is usually clinical with careful history excluding other neuropathic pains. The only blood test the author performs is serum ferritin (replace if below 75). Antihistamines, beta blockers, dopa depleting medication and nicotine all aggravate RLS and should be reduced or removed if possible.
Ropinirole, rotigotine and pramipexole are licensed therapies with effective short and medium term benefit in RCTs but there are now well recognised side effects from all dopamine agonists with impulse control disorder (10-13% of those treated for RLS) and augmentation (occurring at a rate of 7% a year – worsening symptoms, need for more medication and spread of RLS to other body parts). Therefore all need careful ongoing screening for impulsive behaviours. Low dose, once daily gabapentin or pregabalin may be safer and also show benefit in RCTs although remain off license in the UK.
Obstructive sleep apnoea occurs in at least 10% of men and 5% of women over 40 and overweight, but in a surprisingly high 30% of chronic MS patients and in 30-50% of the pain clinic often with help from opioids and gabapentinoids. The simplest screening tool is the STOP-Bang, those scoring over 3 and sleepy should be referred to the local respiratory sleep service. We should all support GPs to reduce inappropriate opioids, the mechanisms of worsening pain are identical to analgesic overuse headache but often with additional daytime sleepiness.
Sleep disorders in the neurology clinic are common with 30% of chronic MS and treatment resistant epilepsy patients having moderate or severe OSA. This tends to be true of any long term conditions decreasing activity and needing drugs that cause weight gain or decrease muscle tone.
Bedtime stories are fascinating, usually treatable and so worth spending a little time learning about. For normal brain function, we all need to sleep well.
Further bedtime reading
- Postuma RB, Iranzo A, Hu M. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019 Mar 1;142(3):744-59.
- Reading P. Update on narcolepsy. Journal of Neurology. 2019;266:1809-15.
https://doi.org/10.1007/s00415-019-09310-3 - https://irlssg.org The International Restless Legs Society Study Group.
