* * *
It seems, therefore, that Disney was right. Bruno the cartoon dog, as well as the King, exhibited RBD years before neuroscientists even reported it in cats, and decades before it was formally recognised by medics. What could be seen as artistic licence turned out to be seminal medical documentation. And, watching Cinderella all those years later, I wondered how many people might have seen this with their children or grandchildren and recognised something of what they or their partners do in the night.
Postscript: In the past few months, John and Liz have resumed sharing a bed, facilitated by a large bolster dividing them. Liz says that there have only been a few episodes; John on one occasion roaring like a lion, but without kicking.
4
RUMBLINGS
When I look through the medical records of my patients, they are full of abbreviations or acronyms. Some, like CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), or SOREMPs (sleep onset rapid eye movement sleep periods), are absolutely necessary, to save ink, time and the sanity of the poor medical secretary typing clinic letters. Others, much beloved by medical students and unspeakably rude or insulting, these days largely only exist as urban legend, having fallen out of usage decades ago. And then there are those that describe what the patient is telling you.
Of all the acronyms in common use, none is more guaranteed to sink the heart of the doctor opening the notes than TATT – ‘tired all the time’. When the presenting complaint is TATT, you know that the consultation is going to be a long one. The list of possible causes of TATT is almost endless. Underactive thyroid gland, diabetes, depression, chronic fatigue, cancer, shift work, anaemia, autoimmune disease, carbon monoxide poisoning . . . it goes on and on. Some of these causes are life-threatening, while others are minor complaints, but TATT is incredibly common, so for the general practitioner, an inordinate amount of time is spent filtering in order to find those with a serious underlying problem: a needle in a haystack.
I am sure that these four letters – TATT – were scrawled in Maria’s* medical notes when she first went to visit her doctor, whose spirits undoubtedly ebbed as he or she listened to her story. When I meet Maria, she is eloquent, vivacious and energetic. But the picture she paints of only a few months ago is hard to envisage.
She tells me: ‘So, over the last couple of years, I was just exhausted all the time. I had no energy. I didn’t feel well and I’d been going to the doctor. I thought maybe it was my thyroid, or maybe I had anaemia, and so I went repeatedly for blood tests and things. I’m overweight and was having real difficulty in losing any weight no matter what I was doing. I had no energy to exercise.’
Maria, now in her forties, was juggling motherhood and a challenging job in healthcare, but her sheer exhaustion was impacting all aspects of her life. The sense of fatigue was all-pervading. ‘I think one of the things that I found very difficult was that I veered between extremes of being very manic and just really furious. I had no sense of perspective. I had no resilience. I couldn’t cope with anything.’
She could just about cope with work and home life, but any slight deviation, any additional pressure, was intolerable. ‘Any little bump in the road was like the worst thing that had happened to anybody ever. I’m quite a cheery person by nature and my sense of humour went.’
Maria’s lack of energy was having a significant effect on her relationship with her husband. She recalls:
He’s a very laid-back person, but there were a few times he said to me, ‘This has got to change. This can’t carry on.’ But he knew I was doing everything that I could. I was trying meditation, I was doing mindfulness, I was trying to go for yoga classes, I was trying to change my diet. I even changed my job. There were lots of things that I was doing all the time to try to get back to who I should be.
As I listen, I am struck by the lengths that Maria went to in an attempt to improve matters. Changing your job is not a minor change, after all, but a real upheaval.
Her poor health was having physical and psychological consequences, too. Maria recalls her distress: ‘My skin wasn’t great. I’d always had really clear skin and then all of a sudden I developed eczema on my hands, also across my face and my eyes. I found that very upsetting. I did feel like I was falling apart. I thought, That’s it. I’m kind of freewheeling down to menopause and I’m just crumbling. It felt very unfair.’
And for Maria’s husband, it was a struggle too.
My husband was worried, but he was also frustrated because he was having to deal with the fallout of me not being rational, not having energy to do things, and making plans and then not being able to follow up with them because I was too tired. It killed our social life because I just wasn’t able to go anywhere. I was just too tired. So I’d make plans full of optimism and then, when the time would come, I wouldn’t be able to go. You can only do that so many times before people stop making plans with you because you’re a flake.
She recalls that, if she had a day off, she would take her children to school, come home and get back into bed, setting her alarm for twenty minutes before she had to pick them up again. ‘I didn’t have the energy to read a book because as soon as I started reading I’d be asleep before I got to the end of the page.’
Predictably, the problems weren’t just confined to her home and social life. At work, Maria would have to pinch herself under the table in meetings to make sure that she didn’t doze off. ‘I would find it very, very difficult to stay awake, so I’d have lots of coffee, lots of glucose energy sweets to keep me going.’
Maria battled on, but repeated trips to her doctor did not result in any clear diagnosis, or any prospect of treatment. However, some eighteen months after first seeking medical help, Maria had a lightbulb moment. She remembers it vividly: ‘I was at the doctor’s for something else, and an information video came on the screen in the waiting room describing some symptoms, and I thought, Gosh, that sounds like what I have! So, when I went in to see my GP, I said, “I think I’ve got sleep apnoea!’ ”
* * *
Snoring is both the subject of comedy and an instrument of torture, particularly for those sharing a bed with a snorer. It is incredibly common. For most people, a narrow airway or partially blocked nasal passages disturb the airflow at the back of our mouths, causing the soft tissues in our throat – the soft palate, tonsils, adenoids and uvula (the dangly bit that hangs down at the back of the throat) to reverberate. As we breathe in, the turbulent airflow causes these areas of the airway to vibrate, resulting in anything from a gentle purr to volumes as loud as a passing lorry.
Obstructive sleep apnoea, however, is of a different order of magnitude, not in volume but in effect. As you drift off to sleep, the countless small muscles that contribute to the stiffness of the walls of your airway slacken a little. If your airway is narrow enough or becomes sufficiently floppy as you drift into sleep, it can actually partially or completely obstruct. This collapse of the airway results in oxygen levels falling and the heart rate increasing, but from a sleep perspective causes a disruption of your sleep. As the depth of your sleep is fragmented, muscle tone in the airway returns briefly to allow you to breathe again, and this cycle can continue throughout the night. These obstructive events can happen ten, twenty and, in rare cases, even 100 times per hour. And if your sleep is disrupted at these sorts of levels, it is entirely understandable why you might wake up tired.
Maria says, ‘I knew that I had an issue with snoring. My husband had said that my snoring was particularly loud, but I dismissed it because, in my experience, lots of people snore, so I didn’t think it was that big of a deal. A bit of a comedy thing, snoring, so I didn’t treat it with probably the gravitas that I should have. I didn’t take it seriously.’
Nevertheless, the evidence of Maria’s sleep disruption was in plain sight. Her snoring was loud enough for her husband to regularly seek sanctuary in their toddler’s bedroom, and he had commented that occasionally she wou
ld stop breathing in her sleep.
While it was obvious to her that she had issues with her sleep, Maria had an alternative explanation.
Although I was exhausted, I was sleeping. I’d been asked by my doctor, ‘Do you sleep all right?’, and I do. As soon as my head hit the pillow, that was it, I was out like a light – whatever time I went to bed. And although I used to wake frequently in the night, I thought it was a bad habit that I had got into from when my children were still breastfeeding. Neither of them slept through the night very well, so I thought I’d just got into the habit of waking up frequently. So I put it down to that. But I never felt refreshed, never.
The severity of sleepiness associated with sleep apnoea can be extreme. At our centre, we have had countless patients whose sleep apnoea has come to light after they have fallen asleep at the wheel of their car and had an accident. I vividly recall one patient who I saw in my epilepsy clinic. He had collapsed several times while standing, and was being investigated for seizures. On one occasion, he was standing next to his desk at work and remembered feeling a little sleepy. When he regained consciousness, he was lying on the ground, blood spattered across his desk and his face, having broken his nose as he slumped face first onto the corner of the table. Investigations for epilepsy came to nothing, but he was found to have terribly severe sleep apnoea. As soon as this was treated, his collapses completely stopped.
We are living through a sleep apnoea epidemic. A recent Swiss community study suggests that up to one in two men and one in four women have significant problems with breathing in their sleep. The rates of sleep apnoea have increased in parallel with our girths and neck circumferences. As we get larger and heavier, sleep apnoea becomes more and more common. In the UK, 62 per cent of adults in 2014 were deemed as overweight or obese, compared to 53 per cent a couple of decades earlier. This increase in size in recent years has been mirrored throughout most of the developed world. In the US, graphs of obesity in the US population show a relentless slope upward, particularly since the early 1980s.
This association between obstructive sleep apnoea and obesity has long been understood. Charles Dickens, that keen observer of medical Victorian London, wrote in The Pickwick Papers of the obese boy Joe: “ ‘Sleep!” said the old gentleman, “he’s always asleep. Goes on errands fast asleep, and snores as he waits at table.’ ” It was this character who led to a variant of sleep apnoea known as obesity-hypoventilation syndrome to be called Pickwickian syndrome. Actually, there are even earlier references to sleep apnoea, or something like it, associated with obesity. Take Dionysius, the tyrant of Heraclea Pontica who reigned in the fourth century BC. He was said to be enormous and terribly somnolent, and his servants resorted to long needles to jab him awake. Another historical character, Magas of Cyrene, died in 250 BC, ‘weighted down with monstrous masses of flesh in his last days; in fact he choked himself to death’, according to rhetorician Athenaeus.
Increased weight may precipitate or worsen sleep apnoea in several ways. Local deposition of fat in the neck makes the airway narrower and more likely to collapse, but fat on the chest increases the effort of breathing, reduces lung volume due to weight on the chest, and increases the metabolic demands on the body. And weight loss often improves sleep apnoea.
But obesity is not the only cause. Sleep physicians will sometimes see people of normal weight with astounding levels of apnoeas – pauses in breathing overnight. While Maria is overweight, she is not obese. There are multiple other factors. Sleep apnoea may run in families, and is often related to the shape of the airway. A large tongue base or a recessed lower jaw will cause a narrowing, as sometimes do very large tonsils. Sleep apnoea appears to be more common in people of Southeast Asian ancestry, perhaps related to the shape of the head and resultant shape of the airway.
* * *
The effects of having your sleep disrupted several times an hour obviously result in excessive sleepiness and feeling unrefreshed during the day. This in itself can be dangerous to your health. Having sleep apnoea increases the risk of a road traffic accident by two or three times. But it is not just sleepiness that we need to worry about.
We know of many physical and mental consequences of sleep deprivation, and being partially woken throughout the night is simply another form of this. But these repeated suffocations also have costs above and beyond simply damaging your sleep. With each obstruction, there is a surge of noradrenaline, a rise in heart rate, blood pressure, and an increase of pressure in the chest, a stiffening of the arteries, and a drop in oxygen levels. We are slowly starting to fully appreciate the wider significance of these physiological changes happening hundreds of times per night. With each pause in breathing, changes to blood flow back to the heart result in alterations to a hormone called ANP, which is secreted by the cardiac atrium. The effect is that the kidneys continue to produce more urine than they otherwise would overnight, which results in more frequent nocturnal urination. Maria recalls: ‘I’d get up probably three, four or five times in the night [to urinate].’
It has now been recognised that sleep apnoea is strongly associated with high blood pressure and the serious problems that it can cause, such as heart disease and strokes. Recurrent jolts of sleep disruption in themselves cause spikes in blood pressure, entirely independent of drops in oxygen, but it seems that intermittent low oxygen levels have an additive effect. In combination, the sleep disruption and effects on oxygen levels act to prime the body to generate high blood pressure during the day through changes to the sympathetic nervous system (the neurological mechanisms that utilise adrenaline and noradrenaline to mediate the ‘fright-fight-flight’ response) and to kidney hormones, which also regulate blood pressure.
So, while high blood pressure in itself is one of the largest risk factors for cardiovascular disease and stroke, there are additional effects of having sleep apnoea. The thin internal lining of blood vessels, the endothelium, has an important function: it detects changes in blood flow and releases substances that regulate the calibre of blood vessels in response. This normal functioning of the endothelium is impaired when blood pressure is high, and this dysfunction is considered an early stage of cardiovascular disease. Experimental models of intermittent hypoxia – recurrent drops in oxygen – suggest that these fluctuations in oxygen themselves lead to endothelial dysfunction, and therefore increase the risk of arterial problems.
Moreover, it is not just the blood vessels themselves that are at risk. Within all our cells, a number of antioxidant mechanisms are in place to protect us from the toxic breakdown products of oxygen metabolism, termed ‘reactive oxygen species’. Intermittent hypoxia results in a decrease in these antioxidant mechanisms, and puts our tissues at risk of these reactive oxygen species when the oxygen levels rise again.
As if that was not enough, it seems that sleep apnoea has other effects that compound the risk. While we know that sleep apnoea is strongly associated with obesity, it may be that sleep apnoea actually contributes to weight gain and related problems. The intermittent hypoxia that is a feature of sleep apnoea has been shown to fundamentally influence the effects of insulin, the hormone that controls the breakdown and storage of glucose that is crucial to the prevention of diabetes. Sleep apnoea lessens the body’s response to insulin, causing what is termed insulin resistance, the first step in the development of diabetes, and results in higher blood glucose levels.
Sleep apnoea also influences the levels of two hormones called leptin and ghrelin, important for the regulation of appetite and metabolism. So it may be that sleep apnoea in itself increases calorie intake and how those calories are processed, predisposing to further weight gain. What’s more, the intermittent hypoxia of sleep apnoea also has profound effects on fat itself, causing inflammation in fat tissues, which may increase the risks associated with obesity.
Thus it seems that sleep apnoea potentially represents a perfect pathological storm when it comes to damage to our blood vessels. The combination of sleep deprivation and ep
isodes of low oxygen gives rise to diabetes, high blood pressure, and inflammation and damage to our blood vessels. The weight gain that it causes just makes everything worse.
Respiratory physicians have been tackling sleep apnoea and its resultant effects for decades, but we neurologists are arriving late to the party. We really only considered it as a diagnosis to exclude in patients in whom narcolepsy was being investigated. I recall as a junior doctor sitting through a presentation on sleep apnoea and being underwhelmed; it was a straightforward diagnosis, with a straightforward treatment, of little relevance to my patients. At the time, the implications of this condition were less well understood, but we now know that sleep apnoea has far-reaching ramifications in the world of neurology too.
Apart from the risk of stroke attributable to high blood pressure and blood vessel disease, sleep apnoea is also a risk factor for an irregular heart rhythm that can predispose clots to form in the heart, before shooting off to obstruct blood vessels in the brain. Sleep apnoea is also of relevance to headaches such as migraines and morning headaches, can result in increases in pressure inside the skull and can worsen the effects of Parkinson’s disease.
Within my own clinical practice, it can trigger sleepwalking, sleep paralysis and nightmares, and can complicate narcolepsy and insomnia. Perhaps most importantly, in my epilepsy clinic I see many patients in whom sleep apnoea complicates their epilepsy control. Sleep deprivation is a potent trigger of seizures in some individuals, and the disruption of sleep by sleep apnoea, as well as the irritation of the brain by recurrent low oxygen, can make the control of epilepsy much more difficult. Recognition and treatment of severe sleep apnoea can make a big difference to some people with this condition.
From the perspective of the general population, one of the most worrying, but also potentially exciting associations, is that of Alzheimer’s disease. While sleep apnoea appears to cause significant deterioration in various aspects of cognition, like attention, vigilance, long-term verbal and visual memory, reasoning and problem-solving, it may also have a direct role in the development of dementia. Sleep apnoea appears to hasten the development of cognitive impairment and Alzheimer’s, and treatment of sleep apnoea in Alzheimer’s causes an improvement in cognitive function. In the elderly, build-up of the protein beta-amyloid has been associated with sleep apnoea. This protein is deposited in the brain, forming plaques that cause signalling problems between neurones, triggering inflammation within the brain, and are one of the microscopic signatures of Alzheimer’s disease. And recently, an explanation for this association between sleep apnoea and dementia may have been forthcoming.
The Nocturnal Brain Page 8