One day not long before I turned 12, I got my first migraine. I was triumphantly competing for my primary school in a regional cross-country race when zig-zags of neon light began to buzz in my peripheral vision.

Then suddenly they were gone replaced by swathes of nothing, like Photoshop had just chopped out chunks of the path ahead. The race ended with me projectile vomiting into a garbage bin by the side of the road.

That afternoon, I cowered in a bedroom back at home, enduring a headache that no standard painkiller could touch.

When my mother took me to the doctor soon after, I described in detail the crazy vision, the pounding headache, the dramatic vomit and the next two days spent tiptoeing around dark rooms as the slightest vibration or sliver of light threatened to set things off again.

"Welcome to the world of migraines," said the GP, who had seen it all before.

Migraine sufferers, or "migraineurs" as they're termed, get pretty antsy when anyone with a bad headache calls on this diagnosis. Those of us who have experienced one know (as the clich goes) this is far, far more than a headache.

But the story of migraine isn't just a tale about the mistaken identity of pain.

For many it is a story of chronic disability and economic loss, it affects women three times more often than men and the latest research has drawn unsettling links to the risk of everything from depression and endometriosis to an increased chance of stroke.

Yet research funds are extremely difficult to come by and as a result, precisely how genetics, hormones and lifestyle interact to cause migraine, let alone universally effective treatments, is still being worked out.

Migraine is a mysterious condition and yet surprisingly common. About 12 per cent of Australians have experienced one and migraine makes a lot of top 10 lists: it is the world's most frequently diagnosed neurological problem; a leading cause of disability in Australia and the third most-common medical problem globally behind a hole in the tooth and a standard headache.

In 2018 alone the economic cost to Australia was estimated at more than $35 billion.

Like me, Lyn Griffiths got her first migraine as a child. But her mother suspected immediately what was up because she suffered from migraines too. When Griffiths' son started complaining of head pain at five years old, it didn't take long to join the dots.

But there's more to Griffiths' story than her family link to migraine.

She is better known as Professor Lyn Griffiths, a molecular geneticist and the executive director of the Institute of Health and Biomedical Innovation at the Queensland University of Technology, where she has pioneered international research into migraine and DNA.

"About 50 per cent of the time people who suffer from migraine have another close relative that also suffers," says Griffiths. "It was pretty obvious that there was a strong genetic component and as a geneticist with migraine in my own family that was interesting to me. I thought someone ought to be looking at this from a genetics perspective."

In 1998 Griffiths' research found the first gene linked to migraine. Since then genes responsible for two kinds of migraines including a deeply traumatic version known as a hemiplegic migraine that can cause paralysis and even coma have been discovered.

The genes for hemiplegic migraine are "heritable and causative", she says. That means if you have them you will definitely get this very severe form of migraine and can pass the gene mutation to your children who each have a 50 per cent chance of developing migraine too.

But the second and more common migraine is no walk in the park. Sure, sufferers don't lose consciousness, but they don't escape the hallmark pounding one-sided headache, light and sound sensitivity and nausea. For 20-30 per cent in this group, like me, there is also what's known as an aura causing vision changes and sometimes speech disturbances

Raphaella Crosby suffers from hemiplegic migraine. During an attack she typically loses her vision and become paralysed down one side of her body.

"What happened to me seemed too intense to be a migraine and it took me years to accept it," says Crosby, who had her first attack at 22. "It felt like my body was malfunctioning in really strange ways, I couldn't see, couldn't speak, couldn't lift my arms and parts of my body were numb."

An attack in 2012 put her in hospital for 10 days. After tests for everything from multiple sclerosis to lupus, the diagnosis was migraine.

"I didn't really recover from that point on," says Crosby, now 43. For the next seven years the migraines came one after another "until they all blurred into one".

Migraine cost Crosby her career, her friendships and any chance of a normal relationship. Eventually she took a disability pension and started using opiates to cope with the pain. "Things got really bad and I was going to hospital regularly," she says. "You get to a point where it's migraine all day, every day. I would often be completely paralysed and require care. I had to concede defeat to the beast."

Then 16 months ago something miraculous happened. Crosby joined the trial of a new class of drugs developed from the research of people like Griffiths. These drugs work by suppressing a peptide that soars in migraine patients during an attack.

Crosby's response to the medication was lifechanging. "I'm a super responder," she says of the monthly injections of a substance called erenumab-aooe, which is not a silver bullet for most people. "Only about 25 per cent of people respond as well as me and it's transformative because I thought I was totally and permanently disabled."

But there's a catch. The drug one of five in a new crop of similar medications that target and suppress calcitonin gene-related peptides, or CGRP is not listed on the Pharmaceutical Benefits Scheme.

Crosby received it for free while she was on the trial but now pays $695 a month to continue treatment. It's a big outlay for someone who is only just trying to rebuild a working life.

She has sold assets to pay for the medication over the next few months and is nervous about giving up the only effective treatment she has ever found.

"Where I'm at now is thinking about going back to work, knocking out my PhD, having a life again," she says. "I'm making friends. Life is good."

In the past 20 years at least 50 genes have been found that to relate to migraine.

But the complex web of influences that lead someone to actually suffer an attack are yet to be fully unravelled.

Instead, experts like Griffiths and Melbourne-based neurologist Tissa Wijeratne talk about "susceptibilities" and "triggers", as well as causes.

Migraines have long been associated with eating things like chocolate or drinking red wine. "We think certain perfumes, certain foods and even barometric pressure changes can be the triggers for those who are genetically predisposed," Griffiths says.

For Crosby, while her genes drive the condition, her triggers include dust and preservative 202, potassium sorbate, which is often found in things like yoghurt and sparkling wine. Crosby calls it "my kryptonite": "If I have even the slightest amount, I'm in all kinds of trouble".

Archaeologists have found references to migraine in ancient human civilisations and yet there seems to be no evolutionary benefit to maintaining migraine susceptibility in human DNA. I asked Griffiths why she thinks it hasn't been bred out of us.

She points to the work of Harvard neurologist Elizabeth Loder who has hypothesised that in fact there was a benefit. If migraine was triggered by an incoming storm or an approaching herd of wild animals then the migraineur hiding in the back of the cave had a survival advantage.

I grew out of my childhood migraines but a few years ago, soon after the birth of my third baby and quite out of the blue, I had another episode.

This time a peculiar numbness crept across the tips of my fingers on one hand and when I tried to speak only gibberish came out. I could not read or write as words and letters bounced all over the page. A short time later I experienced a ferocious headache. And there was vomiting.

"I suspect you'd like a scan of your brain?" the doctor deadpanned when I went for a check-up. The all-clear meant one thing was most likely: the migraines were back.

As an illness that affects 18 per cent of women but only 6 per cent of men, Wijeratne says it's a given that female hormones are also one of the culprits. This helps explain why migraine is linked to things like endometriosis and often emerges during puberty, childbirth and menopause.

It is possible that some of the gene mutations related to migraine risk are passed on by the X chromosome, Griffiths says, and because women carry two copies of X, their risk of inheriting the condition is higher. She is also researching how mitochondria, which are inherited maternally, may also potentially pass on genes involved in susceptibility to migraine.

Wijeratne specialises in treating migraine and is a sufferer himself. He began his career working with stroke patients but soon realised that many who turned up for treatment were what he calls "stroke mimics" like Crosby, not suffering from stroke at all, but migraine.

Wijaratne now has around 17 different medications to choose from when treating patients ranging from triptans to CGRPs, but he says coming up with an effective dose and combination remains trial and error.

Part of the reason for this, he believes, is a lack of funds for research. Migraine research attracts just 0.07 per cent of medical funding, says Wijaratne.

Griffiths sighs in frustration when funding is mentioned. "It's the hardest thing in the world to get funding for migraine research," she says. "It's one of the most common neurological disorders and yet one of the lowest on the scale for funding to support research."

Wijaratne agrees: "It has links to every human health condition under the sun including cardiovascular disorders," he says, emphasising that migraine patients take their own lives two-to-three times more frequently than the wider population.

"Migraine is definitely the most neglected, worst managed and most under-recognised medical disorder worldwide, wherever you are," he says. "If you have cancer, multiple sclerosis, Parkinson's disease or stroke, you can actually see the disability. If you suffer from migraine you can't see anything although the suffering is unbelievable high."

This is a comparison Crosby can relate to having also experienced what she describes as "a minor skirmish with breast cancer".

"People find it very confronting when I say that breast cancer was nothing compared to migraine," she says, explaining that the emotional and medical support she received as a cancer patient far exceeded her experiences with migraine treatment. "I don't say it a lot because I don't want to offend people who have had very difficult battles with cancer but mine was caught early, dealt with and off I went."

Wijaratne encourages patients to use therapeutic treatments ranging from acupuncture and Botox injections to meditation and yoga all of which have scientific studies supporting effectiveness in some patients, he says.

Neuromodulation in which electric currents are used in the brain is a newer treatment with promise.

And so are "nutriceuticals", where vitamins not pharmaceuticals are used to supplement deficiencies that are now known to kick off a migraine. These include vitamin B2, magnesium and Q10, but one of the most promising is folate, a B-group vitamin that is found in green leafy vegetables.

A mutation on the gene methylenetetrahydrofolate reductase (known as MTHFR) can make carriers susceptible to migraine with aura, Griffiths says, and this gene reacts strongly to folate levels in the diet.

MTHFR is also what Griffiths calls a "susceptibility gene" for stroke and may help to explain the migraine-stroke link.

The stroke risk underscores the importance of a healthy lifestyle if you are a migraine sufferer, says Wijaratne.

"If you are a patient with migraine and visual aura then the increased stroke risk is small," he says. "However, if you add any other risk factor. Let's say you pick up smoking, or don't eat well, don't sleep well, don't maintain blood pressure, then your risk goes up as much as 12 times."

Some patients don't respond to existing treatments, Wijeratne says, but he is adamant "one should never lose hope".

"If a doctor says 'I've tried everything', then choose a different doctor. You should always be hopeful."

Raphaella Crosby is a founding member of patient advocacy group Migraine Australia.

Excerpt from:
Migraines strike women three times more than men, and we're finally starting to understand why - ABC News

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