Thread by @garwboy

Taken me several days to answer this, because migraines have long been a gap in my knowledge

Can't feel too bad though, because the science of #migraines is WAY more complex and uncertain than most would have thought

Here's what's known

Strap in, this will get complicated

/1

https://twitter.com/camposdezafiro/status/1550468315071631360

What is the root cause of migraines? Currently 'TBC', unfortunately.

But evidence suggests it involves neurological, vascular, hormonal and genetic factors are working in concert

Applies to pretty much anything in the brain, it never makes it easy

/2

But if there IS one specific 'root cause' of migraines, most fingers point to Cortical Spreading Depression, CSD

What's that?

It's when a neuron, brain cell, experiences a sudden burst of activity (depolarisation), followed by a period of inactivity, as if it's exhausted

/3

But because neurons in the brain are interconnected and communicative, this sudden burst of activity followed by inactivity spreads to the neighbouring neurons and beyond, so you get a 'wave' of this bizarre neuronal activity, travelling along the brain.

/4

The weird thing here is, while neurons can normally bounce signals and activity around your brain at something close to the speed of sound, in comparison this Cortical Spreading Depression wave travels veeeery slooooowwwwlllyyy

en.wikipedia.org/wiki/Cortical_…

/5

Whereas neuronal signals are normally batted around hyper quick like messages in a busy WhatsApp group, Cortical Spreading Depression diffuses through the brain cells like a drop of ink on a bit of kitchen roll or blotting paper.

It's a gradual thing, basically

/6

Consensus is that Cortical Spreading Depression occurring in the brain leads to migraines, albeit via a still-unclear mechanism. But 'brain cells not doing what they're technically meant to be doing' invariably ends in physical/mental issues of some sort, so it makes sense

/7

Cortical Spreading Depression being the underlying cause of migraines also makes sense when you consider the very slow speed of it. That would explain why #migraines last so long, and also how you can 'feel them coming', via the prodrome stage etc.

americanmigrainefoundation.org/resource-libra….

/8

If you're a regular migraine sufferer, your brain will have ample time to learn to recognise the early sensations of a Cortical Spreading Depression occurrence, and that it means bad stuff is coming in a few hours. Because of the bizarre slow progress of the activity

/9

Aside: Am I OK to say 'migraine *sufferers'? I don't with mental health issues as it's often unhelpful to assign clear (negative) value judgements, but I've not met anyone who experiences migraines whose attitude is anything other than 'THIS IS BULLSH*T MAKE IT STOP!"

/10

But even if we accept that a slow-moving wave of neuronal depolarisation and subsequent inactivity are what leads to a #migraine... how? How do we get from A to B?

Well, that's less clear. There are a lot of contenders though, and it's widely agreed that all play a role

/11

Hardly surprising, though, that 'a wave of anomalous neural activity is spreading through the fundamental areas of the brain' leads to bad stuff happening. Like saying "We released an enraged bull in a busy supermarket, it resulted in a mess". Yeah, ya reckon?

/12

But anyway

This spreading wave of atypical neuronal activity affects many things that could feasibly lead to #Migraine.

One that many agree is particularly important is the effects it has on blood vessels in our brain and head

frontiersin.org/articles/10.33…

/13

Because of the way it feels, migraine was believed to be a vascular issue for many years, not a neurological one. But modern evidence argues that it's like to be a combination, because of course it is

frontiersin.org/articles/10.33…

/14

In truth, drawing a distinct divide between neurological and vascular at this cellular level is probably pointless. Neurons depend on changes in blood vessels to do what they do, and neurons regularly directly change the properties of blood vessels while doing what they do

/15

Ultimately, changes in the behaviour of blood vessels to important regions of the brain and surrounding tissue (like the meninges) can be just as impactful/disruptive as changes in neural activity. There's a lot of overlap. All can/do contribute to migraine.

/16

There's a lot of scientific back and forth as exactly what part of the brain or surrounding tissue, and whether it's more neural or vascular, is the case with migraines. It's all ongoing. But, as ever, the most likely answer is that they all factor in

/17

There are some particular areas of interest

Much #migraine research focuses on the trigeminal nerve

beyondexceptionaldentistry.com/blog/where-mig…

The fifth cranial nerve, it is a triple-branched nerve that supplies information from the head and face to the brain, and provides muscular control

/18

The trigeminal nerve, among other things, transmits sensations of pain from the face and jaw, which is apparently a common experience for migraine sufferers?

nhs.uk/ipgmedia/natio…

Would be consistent with the trigeminal nerve having a key role, in any case.

/19

One argument is that the Cortical Spreading Depression causes vasoconstriction (expansion of blood vessels) in the trigeminal nerve, putting pressure on it, which is interpreted by your brain as pain. Because that's how it usually experiences such things.

/20

Could also explain some links between stress and migraine. Stress can often be expressed by jaw clenching and similar unthinking responses. If your trigeminal nerve is already prone to #migraine, this could cause even more pressure on it, triggering an attack.

/21

Others point to the tissues surrounding the brain, like the meninges, suggesting they can be briefly inflamed, or affected by the anomalous neural activity, and thus experience blood vessel expansion and subsequent pain

pubmed.ncbi.nlm.nih.gov/19457286/#:~:t….

It's all a rich tapestry

/22

There's buckets of complex stuff I haven't even begun to address yet, but that's just how complex migraines are.

But here are two of the more interesting aspects, I'd argue.

/23

One is that man migraine sufferers also regularly experience auras. Usually visual, but not always. Essentially, a migraine makes your vision go weird, you see blank patches or weird patterns, none of which is actually there. They're often a sign that a migraine is incoming

/24

What's happening when you experience a visual aura? Well the Cortical Spreading Depression, the slow moving wave of anomalous neural activity, has got to your visual cortex, causing unusual and baffling signals that your brain tries to make sense of in your perception

/25

It's sort of like your vision is a cinema projector and the underlying migraine activity has flicked paint on the lens, so you get these weird patterns on the screen that aren't related to anything on the film.

/26

Auras can occur via the other senses too, but then that makes sense as the underlying anomalous migraine activity can spread to the brain regions that process those sense too.

/27

Then there's this; neurons behind the activity underlying #migraines are thought to be regulated primarily by two chemicals in particular

Our old pall serotonin

science.org/content/articl…)%20which%20increases%20during%20attacks.

...and oestrogen

ncbi.nlm.nih.gov/pmc/articles/P…

/28

This offers an explanation as to why, by and large, #migraines affect mostly women.

While men do have and are indeed dependant on oestrogen in many ways, it has a more prominent role in female brains and bodies

Unfortunately, this involves migraine processes.

/29

Insufficient or anomalous oestrogen levels have been associated with migraines, and it may be that, in some cases, that kicks off the whole wave of activity that induces migraines in women. So, that's fun.

ncbi.nlm.nih.gov/pmc/articles/P…

/30

The interplay between migraines and oestrogen could explain why birth control like the pill has been reported as leading to migraines, or other observations that women experience fewer/no migraines in late stage pregnancy or post-menopause

/31

Ultimately, pregnancy and/or menopause does many things, but among those are radically altering the usual activity of oestrogen in the body. That this could lead to fewer migraines being triggered isn't especially far fetched.

/32

Again, there's way more migraines that I've not even brought up yet. Will do a more extensive article about it somewhere proper because a Twitter thread isn't the ideal conduit for it.

But yeah, #Migraines. They suck big time, but are scientifically fascinating, I guess.

/33

At this point I usually point people at my books, but none of them have anything about Migraines. Would still be cool if you bought one/some though, means I can spaff my day away doing long-winded Twitter threads

amazon.co.uk/Books-Dean-Bur…

#Migraines #SciComm #Neuro #Brains

/end