Can migraines be untangled by new medical thinking?

io started yawning, and that was it. That was the sign a migraine was beginning, that I was rolling slowly down that padded cliff. It was inevitable that this would happen half an hour before my interview with neurologist Dr Peter Goadsby, the man forcing the world to take migraines seriously, inevitable but not ideal, so I sipped my water and watched as he scrolled through his Zoom backgrounds. Beach scene? Too casual. Meeting room with framed certificates? Too formal. Home study, with heaving bookcase? Just right.

How much do I know about migraine, Dr Goadsby asked politely, and I took a moment to consider. Da una parte, too much. I have one now, I said. I’ve had them regularly since I was a child, an early memory being the evening I found I could no longer read a book and thought, oh well, nice while it lasted. A couple of years ago I was diagnosed as having had a series of strokes when I developed a blind spot in my right eye and later found that blind spot to be a “persistent aura”, the scintillating light that typically arrives at the beginning of a migraine, but in my case, never left. I have become so accustomed to breathing through headaches that I was reassured when I first felt labour pains – I knew this agony, I had survived it monthly. But on the other hand, I know very little. Something to do with blood vessels? Chocolate?

“Everything you’ve said so far,” he replied, “is unfortunately a very common experience. And that’s what is extraordinary to me. intendo, it’s extraordinary, isn’t it? That you, who seem like not a completely crazy person at all,” thank you, “have managed to go through life not really being focused on that pain. People accept their own normality, is my conclusion.”

He tells a story. invecchiato 17 in Sydney, Goadsby went to get his learning permit before starting driving lessons, but when asked to read the chart on the wall, he couldn’t make out even the largest letters. His mum told him he’d hurt his eyes from studying too hard and a few weeks later he returned, but still couldn’t read the letters. “I always thought I was normal, and then I got glasses. I wouldn’t consider myself stupid, maybe a bit… self-contained. But I realised it’s easy to have something that’s profoundly not normal and not really notice. So I was never surprised when people with headache didn’t recognise what was going on.” Though a billion people suffer from migraine (190,000 migraine attacks are experienced every day in England alone), it often takes a drastic change, like my sight failing, for them to seek treatment.

“It doesn’t matter how severe someone says a headache is – from a broad societal perspective, the thing that really counts is what the headache stops them doing. It’s the disability side of things, because people with migraine are in a very productive demographic. I remind my colleagues and any funders who care to listen, that migraine is a disorder of taxpayers.” It’s an argument that works. “Migraine is finally having its time.”

Though he brushes off the claim with gentle modesty, this is in a large part due to Goadsby’s pioneering research. “It’s due to technology really,” he insists. Two hundred years ago, he offers as an example, people with epilepsy would have been burned at the stake as witches. “So when you think about migraines, which are more complex than most other neurological problems in the sense that there’s no apparent marker – I can look at you, but can’t tell you’ve got migraine – brain imaging is crucial. You can image people’s brain during an attack and it shows differences. That focuses the mind. And specific treatments have been helpful in this regard. If you’ve got a treatment that’s for migraine, that implies migraine must be a thing. Whereas if the treatments are nonspecific,” because in the recent past, people with migraine have been prescribed drugs created to treat other things, like depression or epilepsy, “perhaps it’s not. As that technology has evolved – imaging, genetics, pharmacology, research time – that’s given migraine a leg up.”

Come, ovviamente, has he. Goadsby first became interested in migraine as a medical student in Australia. “The appeal was the challenge and the frustration. It seemed so neglected. It was seen as a ‘silly subject’.” Many doctors believed it was a psychosomatic condition related to stress. And pain disorders are difficult to research, as pain is subjective. Più, there’s the gender thing. Goadsby sighs. “Go back 40 anni. You don’t have to be a rocket scientist to work out that, if three out of every four people with migraine are women, and there’s a comorbidity, a biological problem of anxiety and depression, and there are periods involved, what is that going to produce? Some stupid interpretations from doctors, who say they’re crazy.” He seems really quite cross. “But there’s such profound biology going on, with circulating oestrogen levels, I’ve never understood why they would think it was anything other than biological. You don’t need a craziness explanation, because you’ve got biology sitting in front of you. I think there was a protective mechanism for a long time, where physicians hate to say they don’t know, hate to accept that they’re impotent in something. So the alternative to ‘I don’t know,’ is, ‘The person in front of me is crazy.’ So it’s a disorder of women. So what? Get a grip and move on!"

Nel 1985, Goadsby met a Swedish physician named Lars Edvinsson who shared his interest in a molecule called “calcitonin gene-related peptide” (CGRP), which neurons use to communicate. Edvinsson suspected it had a key role in migraine; Goadsby agreed. They formed a partnership that continues today. And this year, along with Edvinsson and two other scientists, Goadsby won the prestigious Brain Prize. Their discovery that a biological mechanism triggers an attack, where blood vessels surrounding the brain open up causing pain, led to a new group of drugs that stop CGRP getting to its receptor, either by blocking the receptor or binding to CGRP itself. Goadsby had long suggested that there were “nerve-based mechanisms that might be important. But this was resisted by the mainstream for some time, because it didn’t fit with the narrative.” Migraine had long been considered to be a vascular disease, linked to the regulation of blood flow in the brain, rather than neurological in origin. “We turned out to be correct. And fortunately, in science, correct still wins.” Previous treatments had debilitating side-effects and only relieved the symptoms, never actually preventing the migraine, but these new drugs – they’re called Gepants – have been shown to improve the quality of life of many sufferers.

When Goadsby got a message that the foundation behind the Brain Prize wanted to speak to him, he avoided calling back, certain he must have filled in a grant form wrong. Migraine, lui dice, is a “Cinderella problem”. Not all diseases are treated equally – just as Cinderella could only watch from the kitchen as fabulous clothes and marvellous invitations were delivered for her stepsisters, some diseases miss out on research funding, celebrity-led campaigns and public awareness. Upon calling, and being awarded the prize (worth more than £1m) Goadsby said, “Cinderella has arrived at the ball as a welcome guest – and got the glass slipper.”

And since then he has found a niche sort of celebrity. "Il Daily Mail interviewed me,” he chuckles, “and I said, ‘Can I ask, why do you do so much on migraine’? And they said, ‘Because it’s common! We do common!’ I felt like such an idiot. One in three adult females in the country are interested in it, so there’s a chance that someone who picks up the Daily Mail, or indeed the Custode is too. But having come through neurology in an era when ‘common’ was not what neurologists did – they tended to do abstruse and rare – it was an important thing to hear.”

Common. When he said my experience – the pain, the blindness, the ignorance – was common, I was taken aback, slightly hurt. I got over it. But I realised migraine has become as much a part of my identity as my voice or taste in desserts, and oddly personal with it. I am not alone in carrying around a sort of migraine mythology, the feeling that these are not exactly headaches, instead some sort of painful portal, a kind of poem. The author Siri Hustvedt wrote about a migraine aura phenomenon called Alice in Wonderland syndrome, where the “migraineur” (a word suitably pretentious for the community I find myself in) feels parts of their body ballooning or shrinking.

For me it’s usually my hand. I get periods of intense déjà vu, and the yawning, and a kind of quick, swaddling depression. It’s not just a headache, is what I’m saying. Which makes it ripe for artists to play with. Nel Joan Didion'S 1968 saggio In Bed (which she said received a bigger response than anything else she’d ever written), she describes both a “pleasant… euphoria” and the slightly uncanny horror of it all. “I had no brain tumour,” she wrote, “no eyestrain, no high blood pressure, nothing wrong with me at all: I simply had migraine headaches, and migraine headaches were, as everyone who did not have them knew, imaginary.” That no one dies of migraine, lei aggiunge, “seems, to someone deep into an attack, an ambiguous blessing”. Afterwards, purified, “I notice the particular nature of a flower in a glass on the stair landing. I count my blessings.”

It’s partly because these migraine side-effects are so blousy and cryptic that I found Goadsby’s findings on the “premonitory phase” particularly interesting. “People might get some neck discomfort, or some brain fog, like they’re just off their game. They can get some mood change, and they might feel fatigued, they might yawn, they might pass more urine, they might crave sweet things, all before the pain actually starts. What it always sounded like to me,” and what he went on to prove, “was that the attack had already begun.” Previously we might have thought sugar triggered a migraine, but his work showed that the migraine, already slithering its way through the brain, had dragged the migraineur to a sweet shop. “People would have light sensitivity, and say bright lights trigger their attack. But some of this must be that they noticed the light because their attack had already started. The horse had already long since bolted. So to understand migraine, you’ve got to push back even further.”

Goadsby holds a particular respect for the people who willingly acted as his guinea pigs, consenting to attacks being triggered for their experiments. “Frankly, the only reason to do that is because you want to do something good for society. It’s the only logical reason for it, so that never ceases to amaze me. I was talking to someone earlier today who’d had a dreadful 30-odd years of migraine, nothing worked, then went on one of these antibodies and has had, Egli ha detto, nearly three years of feeling just ‘normal’.” He grins. “And you think to yourself, bene? What can I say? ‘Great.’” He laughs. “It’s not a very long conversation.”

What he’s talking about is the end of migraine, a major debilitating disease, one that led a doctor to recently advise me to “come to terms with my disability”. "Sì, this is just the beginning,” he promises. Even those who don’t respond to these new medications will benefit from the increased focus. And eventually the tablets will come off patent, so generic manufacturers will be able to make them for pennies, something he’s particularly excited about. “That’s not just going to change the developed world, but impact poor people who, ovviamente, are just suffering as much, but with many different problems, too – you know, they have to go out and get water – they don’t need the misery of migraine on top. You can’t help but be optimistic when you realise that the world will be a better place. It’s just a matter of being patient.”

He talks about the moments that have led to his breakthroughs, and those that came after, with a fizzing enthusiasm that makes me briefly believe I understand the science, and a little breathless, pure. “One thing that was pretty spectacular – it was the first time that people have done something called ‘immunopharmacology’. So instead of using antibodies to manipulate the immune system, what you’re doing is using the antibody as a drug…” He dashes off to get a parcel from the front door and returns midsentence, casual, “…so to speak.”

An important moment occurred recently, quando, in a consultation with a migraine patient, he realised he was about to write his first prescription for one of the drugs he had created. “There are few examples in my life where I would use the word surreal, but that would be one of them.” Did the patient know that he was responsible for the drugs that would save him? “No.” He looks up, with a very small smile. “And I didn’t think there was any reason to tell him.”

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