The Nocturnal Brain

  Another unusual feature of Janice’s attacks is that they only occur while asleep. She has never experienced them during the day, unless she has had a nap. Surely seizures would arise in the daytime too? Actually, not necessarily. Sleep and epilepsy have been known to be closely linked for well over a century. Many people report that sleep deprivation is a potent trigger for their seizures, that their convulsions will only happen or be more likely to occur after a very late night or an early morning. We utilise this in clinical practice when trying to diagnose epilepsy, by sleep-depriving patients prior to an EEG. In addition to sleep deprivation triggering seizures, it also appears to bring out the electrical fingerprint of a predisposition to seizures on the EEG. And sleep disruption due to other problems like sleep apnoea can also exacerbate epilepsy.

  It is not only lack of or disrupted sleep that does this, however. Sleep itself does something to the abnormal electrical impulses that underlie epilepsy. When we bring patients into the sleep lab, we will start recording their brainwaves before they go to sleep and continue throughout the night. We will often see an entirely normal EEG pattern while they are awake suddenly transform into a very active abnormal EEG as soon as the person drifts off to sleep, even sometimes as soon as they become drowsy. The process of going to sleep in itself seems to facilitate epilepsy. One possible explanation is that, as we enter into non-REM sleep, neurones in the cortex become more synchronised, thus contributing to the uncontrolled synchronous discharges of large areas of neurones that result in seizures. In fact, in REM sleep, when the EEG is most like that of full wakefulness, and the synchronisation of neuronal discharges is least, seizures are least likely to arise, and EEG abnormalities are least likely to occur.

  But that is not all. For some people and some types of seizure, it is the transition from one stage of sleep to another that triggers seizures. I have seen several patients who will have seizures when they move from deeper sleep to light sleep as a result of snoring or other stimuli. Why this is, however, I’m afraid I have no idea.

  There is one type of epilepsy, though, that is most strongly linked with attacks from sleep. Seizures arising from the frontal lobes, the areas of the brain directly behind the forehead and above the eyes, are very frequently much more likely to occur from sleep, and in some patients occur exclusively from sleep. These seizures are sometimes caused by a genetic mutation in genes that contribute to ion channels, proteins that transport salts across the membrane of neurones. These genes, and the epilepsy, are passed from one generation to the next, with over 100 large families throughout the world described in the medical literature. For the majority of those with this condition, however, it is sporadic rather than genetic, often without obvious cause, but occasionally associated with a structural problem in the frontal lobes.

  Typically, frontal lobe epilepsy will start in the teens, with frequent seizures throughout the night. And, as with other forms of focal epilepsy, the manifestations of frontal lobe epilepsy mirror what we know about the function of the frontal lobe. In addition to its role in planning and behaviour, the frontal lobe is intimately involved in movement. At the part of the frontal lobe closest to the back of the head sits the primary motor cortex, and seizures arising here will result in simple twitching or shaking of a body part. But further forward, closer to the face, there are areas of the brain that are responsible for regulating more complex movements, often coordinating actions involving both sides of the body, and areas controlling generation of speech. Seizures arising here will result in unusual, sometimes extremely bizarre, movements.

  The kinds of activities we will see in the sleep lab include patients suddenly waking from sleep, with their legs furiously cycling in the air, arms windmilling aggressively, often accompanied by shouting or screaming. One young woman I look after sits up in bed, her arms flailing, body rocking back and forth, as if possessed by a demon. I have also seen videos of patients uncontrollably performing forward rolls in the bed, or jumping out of bed, hopping up and down with their arms raised and fists clenched, exactly like a boxer sparring in the gym. All of this activity is usually done in full consciousness, but entirely without control, the seizures themselves waking someone out of sleep.

  There is also sometimes a degree of overlap between these frontal lobe seizures and non-REM parasomnias, events like sleepwalking, sleep-talking and night terrors. Some of the behaviours seen in frontal lobe epilepsy are almost indistinguishable from sleepwalking or related disorders. This may be related to non-REM parasomnias being triggered by small epileptic seizures, but it is also possible that there are inborn patterns of behaviour critical for survival, like running or fighting, coded for deep in the frontal lobes, triggered both by seizures and non-REM parasomnias. In practice, distinguishing these two conditions can in certain circumstances be extremely difficult. Sit several ‘experts’ around a video of a patient, and they will often have entirely different views as to what they are witnessing.

  Janice does not describe any of the classic features of epilepsy, though, apart from the fact that her events are very similar each time. The confusion, the speech disturbance, the déjà vu, the hallucinations of smell – the characteristics of temporal lobe epilepsy – are just not there. And the fear of these events is understandable as a response to suddenly being choked out of sleep rather than as an epileptic phenomenon. Nor do her seizures sound like frontal lobe epilepsy, with the exception perhaps of the fact that her events solely arise from sleep. So, if her events do indeed represent epilepsy, where in the brain are these seizures coming from?

  The jerking of the right leg in some of her events points to it coming from the left side of her brain. If these are indeed seizures, this suggests involvement of motor areas, and the left side of the brain controls the right side of the body. Her most prominent symptom is the sensation of choking, or her throat constricting and suddenly feeling throttled. And there is a rare form of epilepsy that can cause this.

  Deep within the brain lies an area called the insular cortex. On either side, roughly just above the ears, the insula sits, covered by an expanse of temporal lobe from below, and frontal and parietal lobes from above, like the teeth obscured by the upper and lower lips. The insula connects to all these regions as well as the limbic system, the areas of the brain involved in emotion. And because of its location, seizures in the insula can mimic other forms of epilepsy, depending on where the seizure activity spreads. Involvement of the limbic system may result in anxiety, panic or fear, and spread to the frontal lobe can cause movements identical to those seen in frontal lobe seizures, like the kicking, cycling or rocking described above. Temporal lobe spread can rarely result in the triggering of areas involved in hearing, causing auditory hallucination like whistling. And involvement of the autonomic system, the aspect of the nervous system involved in maintenance of blood pressure, heart rate and gut movement, can cause churning of the stomach, goosebumps or, in extreme cases, abnormalities of the heart rhythm, to the point of briefly stopping the heart altogether.

  The most common manifestation of insular seizures, however, is usually related to spread to the sensory cortex, the bit of the parietal lobe that overlies the insula. Looking at how sensation is organised in the parietal lobe, imagine a picture of your own body mapped across the brain. It is not true to scale, as areas of the body very sensitive to touch are better represented than those less sensitive parts. The leg, abdomen and trunk are relatively small, while the hand, face, eyes and tongue are grossly distorted, like a caricature. The area of the sensory cortex representing the leg wraps the parietal lobe deep into the sagittal sulcus, in the midline of the brain, and as we move to the side, then the trunk, the arm, the hand. Finally, in the area closest to the ear, an area known as the operculum, the bit of the parietal lobe smothering the insula: the lips, the tongue, the throat. And spread of seizure activity from the insula to this area of the brain results in tingling or other forms of sensory disturbance in the lips, gums, tongue or throat, often associate
d with a feeling of choking, constriction or suffocation. Exactly like Janice. And while our understanding of insular epilepsy has significantly advanced over recent years, even in the 1950s Wilder Penfield, the neurosurgeon who mapped out functions of the cortex using his electrical probe, wrote of insular seizures: ‘A sensation . . . rises to the throat . . . The sensation may be sickening or pressing and may end in a feeling of choking.’

  * * *

  During our initial appointment, I tell Janice that I want to look for evidence of epilepsy. She has already spent the night in the sleep lab, having seen my respiratory colleague. The sleep study only shows generally poor sleep. Sod’s law, she has not had any events overnight, perhaps because this was not done in the week before her period. I organise an MRI of the brain, to look for any abnormalities that might give rise to epilepsy, but it is normal. We undertake a routine EEG, recording for about half an hour while Janice is reclined on a couch. This is also essentially normal. I organise another, this time as a sleep-deprived recording, to see if we can monitor her brainwaves as she drifts off to sleep. This time we see some slightly abnormal activity over the left temporal lobe, not specific to epilepsy, but at least suggesting that there is some abnormality of brain function in this region. I book in a repeat admission to record a whole night, to see if we can capture one of her events but, as luck would have it, again we are unsuccessful.

  I am enormously frustrated by my inability to prove my diagnosis of epilepsy, and Janice is too. Ultimately, she does not care what is causing her events, she just wants them treated. In desperation, I request a PET scan. This type of study involves the injection of glucose labelled with a radioactive marker. The brain is scanned for radioactivity, to look at patterns of utilisation of the injected glucose. Sometimes, areas disrupted by frequent seizures exhibit abnormal function by taking up less glucose than they should. When I see her again in clinic following her scan, the results are definitive. On the right side, the insula glows purple and pink, showing normal uptake of the radioactive glucose. But on the left, it is obviously blue and green, the cooler colours showing much less activity than would be expected. To Janice’s and my relief, the diagnosis of insular epilepsy is confirmed. We can start treatment.

  * * *

  The EEG is the standard way of diagnosing epilepsy. Even recording someone’s brainwaves between seizures can often show tell-tale signs that certain parts of the brain are liable to generate seizures. For certain types of epilepsy, this is an extremely useful diagnostic test, but it does not always give an answer. The definitive test is to capture one of these seizures with the EEG leads attached. We see characteristic changes in the brainwaves as the seizure starts and then spreads through the brain, the signature of epilepsy as it happens. But there are limitations to the EEG; it is not foolproof.

  For certain types of epilepsy, like genetic forms, or temporal lobe epilepsy, most cases can be proven simply by doing one or two standard EEGs, even between seizures. But, as previously discussed, identifying features of epilepsy on the EEG, particularly when the EEG is not recording during an actual seizure, depends upon the location of the source of the seizures. If the abnormal area is small, very deep, or even orientated the wrong way, then simply placing electrodes on the scalp may not detect any abnormalities. And this is a particular problem for seizures arising from sleep. The wrinkles or crevices that cover the brain are especially deep in the frontal lobes, and some of the cerebral cortex that lines the outside of the frontal lobes is some distance from the scalp, with bits of the frontal lobe sitting closer to the eyeballs than the surface of the brain. In frontal lobe epilepsy, the EEG between seizures is often normal. Even if actual seizures are captured, in about half of all patients the brainwaves are either entirely normal, or there is so much muscle activity related to the seizure itself that the activity of the brain is totally obliterated.

  And there is the further complication of these seizures arising from sleep, so that patients and their partners are often unable to give a full description of their events. The diagnosis of frontal lobe epilepsy can be so problematic that some forms were until recent years described as ‘nocturnal paroxysmal dystonia’, a movement disorder rather than epilepsy. It is only with the advent of EEG recorded from electrodes implanted directly into the brain that this condition has been shown to be epileptic in origin. And in insular epilepsy, the same issue applies. The insular cortex is very deep, covered by a thick layer of other areas of the brain, distant from the scalp, so the EEG can be entirely normal as well.

  Even now, I and my colleagues regularly debate whether or not the behaviours we are seeing are nocturnal epilepsy, non-REM parasomnia or some other form of sleep disorder. You may ask why it matters. Why don’t we just start people on anti-epileptic drugs? In Janice’s case, with the benefit of hindsight and experience, I perhaps nowadays would not have performed the PET scan. On the basis of her description and the slightly abnormal EEG, I would now likely start her on anti-epileptic drugs anyway, and have the courage of my convictions. But about a third of patients with frontal lobe epilepsy do not respond to the most effective anti-epileptic drug in this condition, and so ongoing events despite treatment do not rule out epilepsy.

  * * *

  Janice’s response to anti-epileptic medication has been dramatic. When I see her a few months after starting treatment, she tells me that she has had some side effects, although they have largely settled. But importantly, for the first time in decades, she is having good-quality sleep. Her events are still ongoing, but are much less frequent, and much less intense. Over the next year or so, we gradually increase her dose, to the point where she only gets a few seizures in the week before her period, or when she is unwell with infections. Her transformation is amazing. From a state of sheer despair, she is now relaxed, sleeping well, and, for the most part, seizure-free.

  At our most recent meeting, some eight years after our paths first crossed, we talk a little more about the impact of her epilepsy on her life. She remains on medication, and is approaching the menopause. Her hormonal fluctuations have almost ceased, and so have her seizures. She has not had any choking attacks for three months; from having many a night, almost every night, to nothing at all. She recalls both the dread of sleep and the completely overriding sensation of being sleep-deprived, of lacking the energy to do anything outside of work.

  ‘My life has changed a lot now,’ she tells me.

  Before, I couldn’t enjoy life. I tried to with my friends but I just couldn’t because of the condition. It would have been nice to be able to go out with friends on a more regular basis. But I couldn’t be free and do what my friends were doing. This was forced upon me, and I had no other choice but to limit my life. Now I feel that I have been given part of my life back. I feel like I can mourn the loss of my past life. I am starting a new life and doing the things I want to do.

  The sense of rebirth in her is palpable, and I think it is as much a result of restored regular sleep as the resolution of her seizures. But I cannot help but feel sad that she has gone for more than thirty years undiagnosed and untreated. ‘I can’t be resentful or bitter about what happened to me as a youngster. But I do honestly think it would have helped me so much if I had been diagnosed so much earlier in my life. This is not self-pity, but I’ve missed out on all the years of my life. I have missed out on so many things.’

  In Chapter 5, on Robert and his sleep-talking, I have cautioned about taking things at face value. Janice’s story illustrates the flipside of the coin. I suspect that if it hadn’t been for her traumatic upbringing, and the behavioural issues, she would have been taken more seriously. Rather than assuming this was part and parcel of her psychological distress, treated with sedatives and antipsychotic drugs, she would have seen a neurologist sooner. The impact of her epilepsy on her entire adult life may have been lessened.

  And, for me, the lesson from Janice has been to believe what you are being told, or at least not to dismiss matters. It is difficult
in clinic sometimes to unravel the biological from the psychological, and I am sure that I am as guilty as others of jumping to conclusions in the face of someone who is obviously mentally unwell or psychologically distressed. But Janice has taught me to start from the default position of belief rather than disbelief, and to look for clear evidence to support the physical or psychological.

  In Janice’s case, however, an important factor is the rarity of her condition, and the fact that few people are familiar with it. And therein lies her motivation, her intense desire to tell her story: to prevent others with similar conditions from suffering for decades, like she did.

  9

  FLOATING EYEBALLS

  ‘I’ll never forget this one because this is when I realised there’s a problem,’ Evelyn says. Now twenty-four, she has finished her degree and is living back at home with her mother. She speaks with a south London accent, and is dressed fashionably. A brightly coloured African print bandana in her hair is a nod to her Ugandan background. She seems happy, confident and relaxed, at least until she begins to talk about her experiences.

  ‘One time at university, I saw my housemate in my face, but the thing about it was that she wasn’t even there. She’d gone home for the weekend. So when I saw her the next day, I was like, “What was you doing in my room yesterday?”, and she was like, “I’ve just got back. How was I in your room?” So do you know how crazy that is?’

  Evelyn sits and describes this experience with a sense of confusion. For the past five years or so she has been plagued by a range of bizarre hallucinations at night. Since starting her university course, these terrifying phenomena have disrupted her life. ‘You’re seeing actual things happening, but it’s just not real. It’s a figment of your imagination. It’s your imagination taking you to the wildest places and showing it to you in your face. I’ve seen demonic figures in my room, and when I see those things I feel like I’m in hell.’