So what is going wrong with John’s sleep? It is clear that John’s lashing out or howling in the night is a manifestation of dreaming, the type of dream associated with REM sleep, but why is the paralysis not kicking in, leaving Liz at risk of a kick or punch when he is dreaming of tigers, snakes or arguments?
John and Liz give a classical description of REM sleep behaviour disorder, or RBD for short, where that mechanism of paralysis goes awry. RBD is thought to affect less than 1 per cent of the population, and typically comes on in the fifties or later. The disorder is a bit of a curiosity, as it is one of the few medical conditions described in animals before humans.
In the 1950s, Michel Jouvet, at the time a researcher at the University of Lyon studying sleep in cats, began to undertake experiments to better understand how REM sleep is controlled by the brain. During the course of his experiments, he found that damage to a part of the brain called the brainstem, the slender tract that is the conduit of all brain signals to the rest of the body, caused cats in REM sleep to hiss, walk, fight or behave as if they were chasing prey. They continued to show brain activity consistent with REM sleep, but the muscle paralysis expected simply did not materialise. In fact, these cats behaved exactly like Bruno, the dog in Cinderella, chasing Lucifer the cat.
Amazingly, Cinderella had been released in 1950, some fifteen years before Jouvet published his results. It seems that Disney, or at least some of his writers, were scientific visionaries, or at least keen observers of nature.
Researchers speculated that if this sort of thing could happen in cats (and cartoon dogs), then in all likelihood it could occur in humans. Indeed, this kind of behaviour was beginning to be described in scanty case reports in the medical literature in the 1960s, but it was not until 1986 that this condition was formally defined and accepted as a disorder, named REM sleep behaviour disorder.
In some respects, RBD sounds a little like night terrors or sleepwalking. But witnessing it, as we sometimes do in the sleep laboratory, shows it to be quite different. During RBD, the eyes are closed, and the movements often appear purposeless, simple flailing or lashing out. There is little interaction with the external world, and people do not get out of bed. Speech is often not fully formed, usually largely unintelligible, and may be in the form of shouting or swearing. Compare this to sleep terrors or sleepwalking, when people often get out of bed and their eyes will be open as they pick up objects and sometimes act out complex tasks, like the driving we saw in Chapter 2. Speech in these sorts of conditions is also different, in that it is usually intelligible, with fully formed sentences. Sometimes people can have limited conversations, albeit ones that are often nonsensical.
The nature of the dreaming is also different. In RBD, the dreams are stories developing over time, while in sleepwalking or sleep terrors, it is often visual imagery, disjointed in nature – walls crashing down, natural disasters, insects, spiders. Another feature that differs is the timing of these events. Most of our deep sleep is in the first half of the night, and most of our REM sleep is in the latter half. So, while sleepwalking and night terrors often occur in the first few hours of sleep, RBD is much more likely to happen later on, in the few hours before waking.
* * *
John has a range of dreams or nightmares that culminate in RBD. ‘I had one a month or so ago which did involve being extremely angry with somebody who I’m quite frequently angry with. That was a reference to a real-life person,’ he tells me. ‘And at the point I leapt out of bed, I’m sure I was on the point of punching him on the nose. For a pretty non-violent sort of person, that was rather uncharacteristic. It was a gesture of complete frustration – of not being able to understand something, not being understood, not being able to get through to somebody. No doubt if I’d continued with the dream I would have landed a punch on somebody.’
Other dreams are more along the lines of being attacked by animals, like the tiger he has previously told me about. ‘I’m quite fearful of water. One of my horrors is the idea of swimming off Bondi Beach and being chased by a shark or something like that. I’m sure that’s cropped up. I’m obviously rather cowardly about big animals, and big animals have occurred more than once in my dreams.’
Much like Jouvet’s cats, the behaviour that John exhibits includes fighting or running away. But, unlike the cats, there is nothing to suggest brain damage in John. He is active, physically and mentally, without a hint of any brain disorder.
We used to term RBD as ‘idiopathic’, meaning without obvious cause. In some patients, this is thought to have been triggered by certain medications, predominantly antidepressants. We occasionally see families with multiple members affected by RBD, suggesting that at least sometimes there may be a genetic component. More recently, we have also learned that in young people it can be a feature of narcolepsy, a neurological disorder that causes loss of control over sleep and dreaming. It is very rare to see it as a result of obvious damage to the brainstem, although I recently saw a young man infected with HI V since birth, with a tumour of the midbrain and brainstem, who vigorously acted out his dreams throughout the night. Perhaps the commonest cause of RBD is when it disrupts the sleep of patients with known degenerative brain disorders such as Parkinson’s disease or a related condition called Lewy body dementia, where features of Parkinson’s, such as slowness of movement and tremor, co-exist with cognitive decline and hallucinations.
In the past few years, however, our concept of RBD has been revolutionised. Rather than the majority of people having ‘idiopathic’ RBD, we are learning that it is often a precursor to these neurodegenerative conditions; a very early warning sign of brain conditions like Parkinson’s disease and Lewy body disease. Why this should be the case is slowly becoming apparent.
The brains of people with these disorders, when studied under a microscope, show deposits of a protein called alphasynuclein. When this protein is deposited in the basal ganglia, an area deep in the brain fundamental to the control of movement, it causes the overt features of Parkinson’s disease that are most familiar to us, like tremor, slow movement and walking difficulties. But studies of brains of people with Parkinson’s have shown these protein deposits elsewhere in the nervous system. These include the nerve that is responsible for smell, the olfactory bulb, and the nerves that supply the gut and blood vessels. Of most relevance, these deposits are also found in the brainstem, the area responsible for switching on the paralysis seen in REM sleep. And, in fact, these changes are seen in people years or even decades before the onset of overt Parkinson’s or other degenerative conditions of the brain. So it makes perfect sense that some people will develop RBD in the very early stages of these brain disorders.
In keeping with the locations of deposition of alpha-synuclein in the nervous system, other symptoms that people frequently complain of years before developing Parkinson’s disease include loss of sense of smell, severe constipation, bladder problems and blood pressure issues. Now, of course, not everyone who has RBD goes on to develop Parkinson’s or other brain disorders, and loss of smell and constipation are incredibly common symptoms, but if we can use these conditions to predict a high risk of developing Parkinson’s disease, then this gives us a window of opportunity. While at present there are no drugs that can prevent or slow the progression of these brain conditions, there are ongoing trials. And it makes sense that, if these drugs become available, candidates for these medications would be those at high risk of developing these disorders, before sufficient damage has been done to the brain to cause more overt features. So, in the future, if I see a patient in my neurology clinic who is of a certain age, with constipation, loss of smell, RBD and other problems, I may simply plug his or her details into a computer which calculates the risk of developing Parkinson’s in the next five or ten years, and decide whether or not to start a drug to prevent this. Efforts are currently ongoing to develop these types of algorithms, to clarify the risk of developing Parkinson’s for any particular individual, but RBD, and other p
roblems, may be fundamental to us treating these disorders in the coming years.
But what about John? He has absolutely no features of Parkinson’s disease or any other degenerative brain condition. He lost his sense of smell a number of years ago, and has some bladder problems, although this is likely related to a previous bladder operation.
* * *
John’s anxiety about his wife’s safety is understandable. Liz is troubled by osteoporosis, brittle bones, meaning she is at risk of fractures. He is worried that he will cause her a serious injury. ‘I’ve been woken up by the prospect of injuring somebody else, but I haven’t injured myself,’ he says. ‘I obviously take it so seriously that until I can find a solution to this, we’re going to have to continue sleeping in separate beds. I’ve been sleeping on the sofa bed for the last nine months. And I’m not intending to go and subject her to a sleepless night until I know that this is not going to happen again.’
Additionally, Liz’s fear of what might happen at night means she finds it difficult to sleep in a bed with him. ‘It was just very frightening. I felt it wasn’t safe to actually fall asleep,’ Liz explains. ‘Because we now sleep in separate beds, I’ve noticed I’m sleeping much better, because obviously I was more fearful than I was aware of.’ On a number of occasions, before this separation, she had woken up in the morning with bruises and scratches.
The cessation of sleeping in the same bed, while keeping Liz safe and comforting John, is clearly not entirely welcome. It must be a huge psychological blow to any couple not to share a bed, and I suspect this change is tinged with sadness for them both. Despite this, Liz does find glimmers of humour in the situation. ‘The only one time I did giggle was, he was lying on his back, and I was relieved he wasn’t lying on his side and facing me, and he kicked out and fell off the bed. But apart from that, it hasn’t been at all funny.’
* * *
There are two things that particularly strike me about John and many other patients with RBD. The first is the nature of the dreaming. John and others clearly describe a dramatic change in the content of their dreams with the onset of this condition. These dreams or nightmares of being attacked, fighting or running away are fairly consistent. Occasionally we do see other sorts of activity, like acting out smoking a cigarette, petting a dog, laughing or singing, but these are much rarer. The behaviours that we see are the very characteristic movements of thrashing, flailing or kicking that Liz describes, often accompanied by swearing, shouting or screaming. So what explains this striking alteration in dream content? It certainly does not appear to be a function of daytime aggression. Liz says: ‘John never really expresses anger. I very rarely see him angry, so that’s also a very strange thing because at night he is very angry and very frightened.’
I perceive John to be a very gentle and mild-mannered man, and indeed multiple studies have shown patients with RBD to have very low levels of aggression in their waking lives. Therefore, could the changes in the brain that occur in RBD directly be responsible for the change in dream narrative? There is some evidence hinting that this might be the case.
A research study has shown that patients with Parkinson’s and RBD are less aggressive during the day than those with Parkinson’s and no RBD, at least suggesting that changes within the brainstem have some role in aggressive tendencies, but certainly this does not give us a full explanation. An alternative, relatively new, hypothesis is that the changes within the brainstem give rise to these flinging or thrashing movements. In the same way that we can integrate sensory stimuli into our dreams – a clap of thunder in the outside world becoming an explosion in our dreams, or a touch on the leg morphing into an animal clawing at us – perhaps these movements, these violent actions, may influence the stories unfolding in our REM sleep.
RBD is also thought to be more common in men than women. Indeed, men make up about 80 per cent of patients referred to sleep centres. Is this because of the effects of testosterone on our brains? Or is RBD simply milder in women than in men? It has definitely been shown that unpleasant dream content in men is more likely to involve verbal or physical self-defence, while in women it is more likely to be a case of a sensation of threat or fear, of running away. So could this mean that women are less likely to lash out, and less likely to injure themselves or their partners? Or could it simply be that women are more embarrassed to seek medical help, or more likely to push their partners to seek attention? We just don’t know.
The other remarkable feature is the contrast in movement between day and night. As Liz comments of John’s episodes: ‘It’s almost unbelievable that he has that sort of force in him. If you asked him to do that in daily life, he wouldn’t have a quarter of the strength.’ In his case, I suspect this is simply a function of the level of stimulation, the fear of being bitten by a tiger or attacked by someone, that releases levels of activity we rarely need to rely on in our daily lives. I think of stories of people exhibiting enormous feats of strength when under intense pressure, like lifting a car to free an injured pedestrian. But what is truly amazing is that people with Parkinson’s disease or related disorders may be crippled by their condition in the day, but may move fluidly and quickly during their RBD. The tremor, slow movements and quiet voice during the day are replaced by vigorous, quick actions and loud shouts at night. It is almost as if their Parkinson’s disease is transiently cured in REM sleep!
In one of the first studies of this phenomenon, the researchers described one patient who was witnessed squatting on the bed, waving his arms as if flying, emitting a siren noise with a duck’s voice. The patient, who during the day had been unable to squat down, was very slow of movement and had a quietened voice, had been dreaming of being a police-duck, flying after a pigeon-thief. Other patients with significant daytime symptoms related to their Parkinson’s have been witnessed engaging in sword fights with an invisible foil, furiously rowing an imaginary paddle to escape from crocodiles in a canoe, or delivering political speeches in a loud voice. But how is this possible?
Some patients may exhibit a phenomenon called ‘paradoxical kinesis’, where movements suddenly normalise under life-threatening circumstances, for example a bedridden patient who suddenly manages to get up and flee his house during a fire. So perhaps in some cases with RBD, the strong emotional content of their dreams may override their Parkinson’s disease. But clearly this would not explain a flying police-duck chasing after a thief, or other examples, such as singing a pop song in the middle of the night while dreaming of being in the shower. It remains speculative, but some researchers have suggested that, in REM sleep, signals from the motor cortex, the part of the brain where movements are generated, simply bypass the basal ganglia, the areas involved in Parkinson’s disease that regulate movement in waking life. Why this should be the case is another of the many unknowns in neuroscience, but remains a fascinating question.
* * *
In addition to John’s RBD, his sleep study has demonstrated mild sleep apnoea – snoring to an extent that he intermittently partially obstructs his airway – and this, as well as getting up at night to pass urine, a sequel to his prostate operation, contributes to his poor sleep. For his RBD, however, he has now started on medication. The mainstay of treatment used to be a sedative called clonazepam, a benzodiazepine similar to Valium, which for some people works very well. It can have side effects, however, and can leave people feeling groggy and lethargic in the morning. For people with neurological disorders like Parkinson’s or Lewy body disease, it can cause confusion or predispose them to falls.
In recent years, we have started to use melatonin in the first instance. This gentle drug, as with sleepwalking, seems to work for a significant proportion of people with RBD, with many fewer side effects. Numerous potential ways in which melatonin may work have been proposed, but its mechanism of action remains uncertain. John has been on melatonin now for a number of months, with some benefit.
John tells me: ‘They’re reducing in frequency since I started tak
ing melatonin. And in fact they’re pretty infrequent now.’ Liz agrees: ‘Since taking the medication, I’m daring to actually believe maybe it’s doing something, maybe he is sleeping a little bit deeper, but not so deep he doesn’t know what he’s doing. I did hear him crying very loudly, like a very strange cry, a couple of weeks ago in his sleep, and I’ve also in the same week heard him laughing his head off in his sleep. So, you know, it’s not quite as violent, but it’s still something that’s coming out.’
John and Liz are still not confident enough to share a bed, but progress is being made. We are slowly increasing the melatonin dose, and trying to treat his sleep apnoea and urinary symptoms. They live in hope that they will get to the point where they can sleep in the same bed. However, giving John a clear diagnosis has also had other benefits. The shame and embarrassment that John felt when he first started having these episodes is waning. Liz sums it up succinctly:
There’s quite a lot of shame involved in this. From the person actually doing the kicking, beating up the person, your partner, your wife, your husband, whoever it is who’s got it. My husband would say, ‘No, don’t tell anybody. Don’t tell anybody about this!’ And I just had to say, ‘I’m not going to keep it a secret. Because it’s not something that one needs to be ashamed of. It’s something that you’re unconscious of. It happens and you don’t do it on purpose.’
The Nocturnal Brain Page 7