The Nocturnal Brain

  Unfortunately, while we understand something of the genetic basis of RLS, its predisposing factors, and something about what happens on a chemical level in the brain, the underlying cause remains a mystery. It is proposed that whatever is going on in the brain ultimately influences neurological function in the spinal cord. Perhaps fibres projecting down from the brain, using dopamine as their neurotransmitter of choice, dampen down circuits that process sensations. When these descending projections underperform, and dopamine levels drop in the evening, the brakes on these sensory processing circuits are taken off, generating these unpleasant sensations spontaneously. This concept of the brakes being taken off may also make other regions of the spinal cord more active than they should be, and perhaps this releases primitive reflexes that are otherwise suppressed, causing the periodic limb movements in sleep that accompany RLS.

  I recall being at a big sleep conference in Minneapolis a few years ago, at a lecture on sleep in animals. A video of a sea-lion sleeping while floating in the water came up on the screen. I was surprised to see its flippers periodically finning, essentially treading water, and was struck by how similar to the leg movements seen in the sleep laboratory they appeared.

  Perhaps, and this is entirely speculation on my part, as with many areas in neurology and sleep, these periodic limb movements are a throwback to our ancestors. In normal life, these reflexes are dampened down, but when things go wrong in our brains, or indeed our spinal cords, it may just be that our evolutionary past comes back to haunt us.

  8

  SEIZED BY THE THROAT

  Imagine you are tasked with mapping the floor of the world’s oceans, from the shallows of the beaches to the depths of the Marianas Trench. It would be reasonable to expect access to the latest gadgetry – fleets of ships equipped with sonar, submersibles and satellite imagery. Instead, you are handed a snorkel and mask. As you wade into the English Channel to start the job, you lower your head in the waves and catch the occasional glimpse of your own hand in the murky waters. You can just about make out the muddy bottom a few feet away from your face. The rest is just nothingness, as the sea floor falls away into the depths.

  When we routinely study the neurological system, similarly, we can only peer into the shallows of the brain. The depths often remain invisible, obscured.

  In the world of neurology and sleep, we rely on the scalp EEG, the electroencephalogram. By analysing the electrical signals of the brain, through the use of wires stuck with glue to the scalp, we look for fluctuations in brainwave activity. The rate and the amplitude of these fluctuations help us define the stages of sleep, as do other features. And when we look for brain disease or epilepsy, we look for abnormal patterns – excessive slowing, sharpening of the patterns or spikes of electrical activity.

  Yet the EEG, first used in the 1920s on humans, is our equivalent of the snorkel and mask. These scalp electrodes are attempting to record brain activity through skin, fat, the skull, and cerebrospinal fluid. The strength of these signals is tiny compared to that put out by the simple act of blinking, the triggering of small muscles in the face and head. Furthermore, the deflections in those squiggly lines – originally plotted by pen on paper, nowadays on a computer screen – do not result from the electrical changes in a single neurone. Rather, it requires the accumulation of impulses synchronised between thousands or millions of neurones, more than 6 or 7 square centimetres of cerebral cortex – the thin layer of cells lining the surface of the brain – all orientated in the same axis. So the detail the EEG gives us is incredibly limited. Only large changes in huge numbers of neurones, all pointing in a similar direction, on or near the surface of the brain, are detectable. This technique, the staple of our investigational tool box and upon which we rely so heavily, tells us next to nothing about what is going on in the vast depths of the brain. Forget about snorkelling in the English Channel, it’s more like wading through a vast swamp.

  * * *

  Some of the people I see in my clinic are like old friends. Janice is one of these. I have known her now for almost a decade. In my mind’s eye, she is always smiling, a dazzling broad smile set in a gentle olive face, completely unlined by the passage of that decade, or indeed the fifty-something years of her life. But behind her cheery demeanour lies a difficult and troubled past. Janice is very open about her traumatic childhood. She was born in the UK and is one of seven children. Her parents had emigrated from Trinidad shortly before her birth.

  ‘My mum’s side was French and Anglo-Indian, and my father was Indian and black. My great-grandfather came from Scotland and that’s how we got the family name,’ she tells me.

  Janice remembers her family home as being very chaotic. Her mother had mental health issues, and she recalls domestic abuse. Her pleasant memories are of her uncle taking her and one of her siblings to Hyde Park for days out, and she still associates this green expanse in central London with a sense of peace, of being carefree. She and her sister would often run away from home, to sleep on the benches in the park. ‘We would bunk the buses, or walk. We didn’t actually always make it to Hyde Park; sometimes we would sleep in Euston station. My sister and I would cuddle up together. The police would come along and find us.’

  At about the age of eleven or twelve, Janice and some of her siblings were taken into council care, and were placed in a children’s home. She has some recollection of a few white couples wanting to adopt her: ‘They [the council] refused because they were white, and they said, “You can’t have children like that, it is impossible,’ ” she recalls.

  Going into care did not improve her lot in life at all. ‘In the [children’s] home, at my [family] home, my whole life was just filled with abuse and violence. And I wasn’t well – [I was] a very sickly child. I was in and out of the hospital. I was very thin, couldn’t eat properly. I was malnourished. Yet everyone ignored me. They chose just to step over me.’

  It is not at all surprising that Janice had behavioural problems. She speaks of being uncontrollable, of responding to violence with violence. ‘If you pushed and shoved me, you were going to get ten times back what you just gave me, which was not very nice.’ Yet the home’s way of dealing with her outbursts was medication. ‘They drugged me up to sedate me, to make me behave. They couldn’t cope with me.’

  For years she was given sedatives and antipsychotic drugs, and remembers being seen at the Bethlem Hospital, the original Bedlam, by a psychiatrist. ‘I didn’t want to take it [the medicine] but I was forced – a child being held down, all these people surrounding you, and you are being forced to take it. I was frightened, so I started fighting with them. I said, “I am not taking the medication any more.” They called the doctor one night to give me an injection.’

  It was in the maelstrom of this traumatic childhood that her night-time events started.

  * * *

  The first time I meet Janice, she is in her late forties. In the consultation, she tells me of her past, but the full details only come to light in the months afterwards. She has been referred to me via one of my astute respiratory sleep colleagues, who in turn has had her referred to him from another sleep clinic in London.

  She describes terrifying nocturnal events that have been plaguing her since she was a teenager. Over the past two or three years, however, these have been getting much worse.

  I ask her to describe a typical attack. She tells me that, as she is dozing off, she feels that her heart has slowed, almost stopped. ‘As soon as I drop off to sleep,’ she says, she suddenly feels a sensation of being crushed, or someone strangling her. The strong feeling of being choked is terrifying, and she fights desperately for breath for several seconds before it eases. When it’s really bad, she will sometimes bite her tongue. Needless to say, she is getting very little sleep. These attacks will only happen while asleep, never while awake, and are happening almost every night. ‘At their worst, they will go on through the night, sometimes fifty or 100 times,’ she tells me.

  Her symptoms
are those of sleep apnoea – collapse of the airway in sleep – but this has already been ruled out by a sleep study performed in the referring centre, and repeated by my colleague. There are some alarm bells ringing in my mind as we discuss her symptoms further. She goes on to tell me that she is sometimes aware of her right leg jerking while she is choking, just a few movements. And there are other unusual symptoms. ‘I feel that maybe my tongue has got bigger during attacks, and I am actually choking on my tongue. And my mouth fills with saliva, sometimes with blood in it from where I have bitten my tongue.’ She also tells me that her attacks are much worse in the few days before her periods.

  Apart from the fear that these attacks cause, she feels destroyed by the terrible sleep deprivation. ‘I have to go to work and just try to function as a normal human being. But I have to struggle and struggle. The only thing that keeps me going is the children.’ She now works as a carer of children with special needs, in hindsight understandable given her own childhood. When she gets home, however, there is nothing left. All she wants to do is sleep, and she will often drift off on the sofa. But even then her attacks will wake her up again. She is fearful of sleep itself.

  I ask her how long these events have been going on. ‘I can specifically remember them since going to secondary school,’ she says. When I ask why it has taken her this long to seek help, she tells me: ‘I would tell my parents about these attacks, and they just totally ignored me. In my household, they had this rule: too bad if you are ill, get out and just function properly; don’t make a fuss.’ Later, in the children’s home, ‘I remember specifically telling them, “I am having difficulty every night with my breathing,” and they just put it down to the fact that this is a troublesome person who has had a difficult upbringing and this is the way she behaves. “She just needs to be sedated and that will take care of it.’ ”

  Janice recalls the first time someone took her symptoms seriously. In her twenties, while staying with her sister, she had one of her attacks. Her sister was so alarmed that she called an ambulance. ‘She actually believed there was something wrong with me,’ Janice says. But, in the hospital, she remembers the doctors dismissing her symptoms. ‘They said it couldn’t have been that bad because I looked perfectly okay.’ So she continued to live with her attacks. ‘I did go to the doctor’s occasionally and mentioned my attacks, and they said, “Oh, it’s asthma,” and I was just put on inhalers.’

  In the absence of sleep apnoea, another explanation for night-time choking is reflux – acid coming up from the stomach and irritating the throat, causing the muscles in the throat to go into spasm. But as I listen to her story, it does not sound like reflux or asthma at all. Nor does it sound like sleep apnoea. I tell her it sounds very much like epilepsy.

  * * *

  Say the word ‘epilepsy’ and it conjures up images of dramatic convulsions, shaking of the entire body, writhing around on the floor with a purple face, frothing at the mouth, and urinary incontinence. For some patients with epilepsy, this is an accurate description.

  In the brain, electrical activity is a highly regulated and precise phenomenon, and it is that precision, that subtle interaction between various neurones, that underlies all our neurological functions: our speech, vision, comprehension, movements, consciousness – everything.

  But epilepsy represents the loss of control of these electrical impulses. Whether due to a genetic condition, or some irritation to the brain like a tumour, infection or stroke, if those processes that tightly control these impulses are diminished, then areas of the cerebral cortex, the grey matter that lines the surface of our brains like the outer shell of a walnut, fire in an uncontrollable manner. The neurones become synchronous, all firing simultaneously (unlike normal service, when they all talk to each other in a highly organised way), disrupting the usual activity of the brain.

  Think of the deck of a ship, with hundreds of people walking this way and that, all in different directions. If all of them run together, from port to starboard and back, the ship begins to sway, and may ultimately capsize. It is these large areas of synchronous electrical activity spreading through the whole brain that result in these convulsions, activating all muscle groups, losing control of movements and of bladder function, losing consciousness.

  However, for reasons that we do not fully understand, in some people seizures do not spread to the whole brain. They originate in one part of the brain, and are limited. They do not propagate widely, and the area of abnormal activity remains restricted to one or a few parts of the brain. In these cases, what these seizures – termed focal seizures – result in is not a generalised convulsion. Rather, the internal and external manifestations of these seizures are a function of which part of the brain is involved.

  And not all seizures result in shaking. The commonest type of focal seizure affects the temporal lobe, in which areas involved in autobiographical memory, language, smell and emotion reside. Patients with temporal lobe seizures may experience a sudden strong smell, disruption of speech, or an impending feeling of doom. Involvement of the memory areas can give rise to déjà vu, that sudden feeling of familiarity that we all occasionally experience, or the opposite – jamais vu – where what should be a familiar environment seems novel, never seen before. If the seizure spreads more widely, it may result in jerking by involving motor areas, or result in confusion, or loss of awareness, but not loss of consciousness.

  I vividly remember as a junior doctor seeing an elderly lady in the emergency department who had been found wandering the streets. This was happening frequently and her GP had raised the diagnosis of Alzheimer’s disease. Upon examining her, however, in addition to confusion, she had some rhythmic jerking of her right hand, a subtle clue of ongoing seizures. An intravenous injection of an anti-epileptic drug suddenly brought her back, and both the twitching and her confusion were resolved.

  Over the years, I have seen some weird and wonderful manifestations of epilepsy, like the young man who would suddenly feel he was upside down in the world, with his vision turned through 180 degrees. His seizures were affecting the parietal lobe, where our brains represent where we are in relation to the world. Then there was the sixty-year-old man whose temporal lobe seizures would result in a feeling of religious ecstasy so intense that he would feel connected to God. He refused to treat his epilepsy, as he worried that he would lose these spiritual experiences. I have seen several patients with visual hallucinations as a result of seizures affecting the occipital lobes, where the visual cortex sits.

  By identifying which parts of the brain are involved in the seizure, and correlating them to the symptoms, we learn something of how the brain is organised, and how neurological functions are ‘localised’. In fact, much of what we know about the localisation of functions in the cerebral cortex comes from the artificial triggering of small seizures.

  In the 1940s and ’50s, Wilder Penfield, an American neurosurgeon, would operate on patients with epilepsy. Before removing diseased brain, he would painstakingly stimulate areas of the cerebral cortex to make sure he was not taking an important bit of brain tissue away. Working on awake patients under local anaesthesia, he would use his electrical probe to trigger small areas of the cortex and see what the patient reported or if they moved. Through this technique, he generated detailed maps of how the brain represents sensation and movement, but also showed that stimulation of the temporal and parietal lobes resulted in symptoms similar to those described by patients having epileptic seizures in those areas – déjà vu, fear, memories, visual hallucinations. A variant of this technique is still used today in people undergoing certain types of epilepsy surgery.

  Indeed, there is a rare natural mimic of seizures being triggered by stimulation of the cortex. Sometimes even stimulating areas of the cortex through mental activity or external stimuli can generate seizures. The commonest form of this is flashing lights causing seizures arising in the visual cortex, but, rarely, even listening to one particular type of music, writing, solving
puzzles or the sensation of hot water being thrown over the head and body can precipitate what are known as reflex seizures.

  So what is it about Janice’s events that suggest epilepsy to me? The first feature is that they are always very similar, if not identical. Focal seizures arise in one particular part of the brain, an area of irritation or abnormal function. So, while different seizures in one person may propagate more or less widely within the brain, the onset of their seizures is identical. She defines her milder events as being differentiated from her more severe events by the lack of tongue-biting, but essentially they are all characterised by the same symptoms. If her seizures were to spread more widely, then there may be confusion or other symptoms, and if the whole brain were to be involved she may also have a full-blown convulsion (she never has). The events that she describes are highly ‘stereotyped’.

  And then there is this curious worsening in association with her periods. It is well-recognised that some women have dramatic changes in their epilepsy as they progress through their menstrual cycle. The sex hormones oestrogen and progesterone have profound effects on the brain, with oestrogen generally making seizures more likely to occur, and progesterone having a protective effect. In the days before a period, the ratio of oestrogen to progesterone is highest. Many women find that this is the time of the month that they are most at risk of seizures. In extreme circumstances, the combined oral contraceptive pill is run through continuously for three months at a time, to limit the number of windows during which women are at a higher risk of seizures.