familial hemiplegic migraine

28 August 2020

“Astrocyte” – A New Migraine Term to Know?

If you’ve followed migraine research over the last few words, it’s likely that you’ve learned a lot of new lingo. Words and phrases like “photophobia”, “cortical spreading depression” and “triptan” have become surprisingly common. But do you know what an astrocyte is? (My spell checker doesn’t have a clue!)

Astrocyte cell — An astrocyte cell
(courtesy GerryShaw)

Let’s back up a bit. You’ve probably heard of neurons. A neuron is a special kind of cell that can conduct electrical impulses. In fact, that cortical spreading depression we just mentioned is a kind of electrical storm in the brain that sweeps through neurons, apparently leading to many of the strange auras that some migraine patients experience.

An astrocyte is another type of cell in the nervous system (the brain and the spinal cord). They get their name from their “star-shaped” form and activity. Astrocytes are extremely numerous – they outnumber neurons at least 4 to 1. But they don’t send electrical messages the way that neurons do. However, they are still very important “communicators” in the body.

Astrocytes have many complex functions in the nervous system. For example, they play an important role in the movement of blood. They play an important role on the way your body responds to viruses. (COVID-19 has the ability to infect astrocytes.) They work together with other cells to transmit pain information. It has been theorized that something “going wrong” with certain astrocyte cells may lead to symptoms of Alzheimer’s.

So what about migraine? Well, researchers were studying familial hemiplegic migraine type 2, a type of migraine characterized by a specific genetic gene mutation. They discovered that this type of migraine seems to cause a malfunction in astrocytes in the cingulate cortex, a part of the brain that processes pain. Basically, what seems to happen is that malfunctioning of astrocytes is related to the malfunction of pain – pain gets out of control.

The astrocytes help control the communication of the neurons. But what if that control isn’t working? What if your brain starts getting more “pain” signals than it should?

In mice, the researchers were able to reverse some of the effects of the genetic problem that is related to this type of migraine by manipulating astrocytes. In other words, to make it practical, we may in the future be able to develop treatments that directly influence astrocytes so that pain signals return to normal – this reducing or eliminating migraine.

Yes, this is a very early discovery related to only one type of migraine. But it’s another one of those small discoveries that could have a huge impact on future migraine treatment.

Although astrocytes may have been largely overlooked when it comes to migraine treatment, they have not gone unnoticed. For example, they were noticed as part of the link between migraine and advanced sleep phase syndrome/disorder many years ago.

And now you’re one of the first to know just a little about the complex and wonderful world of astrocytes.

For more information:

Astrocyte dysfunction increases cortical dendritic excitability and promotes cranial pain in familial migraine (study abstract)
Genetic malfunction of brain astrocytes triggers migraine (brief article discussing the study)
Astrocytes: biology and pathology (detailed discussion of astrocytes, but from several years ago)

26 July 2018

Migraine Genetics: Research more sophisticated, treatment more complicated?

James Discoveries & Stats 0

The genetic basis of migraine may be well known, but we have a lot to learn about how it all works. But recent research is giving us fascinating new insights.

This particular study came out in May and was published in the neuroscience journal, Neuron. Researchers were trying to understand just how migraine is passed on.

migraine genetic traits Basically, two models were investigated. First, Mendelian inheritance. This means that there are a very few genetic traits that are passed on. Depending on what is dominant, they basically predict if the person will inherit migraine or not. We see this in some types of hemiplegic migraine. This probably sounds a lot like what you learned in school about genetic traits.

Second, polygenic inheritance, also known as multifactorial inheritance. In this model, there are hundreds – maybe thousands – of genetic traits that work together. In certain combinations, the person may have migraine.

There’s a third possibility – that it’s really a combination of both. There are some major genetic traits working together with these many less-important traits.

So, for those still reading this article, you’ll be interested to know what the result was. Actually, it surprised the researchers.

First, it was found that the research at this stage is pointing mostly to polygenic inheritance. That is, there is a wide variety of common genetic factors that all work together to result in migraine. This article explains it as being dealt a hand of cards. It’s not the individual cards that make a difference, it’s the hand as a whole.

This was even the case in familial hemiplegic migraine, which has traditionally been the most specifically genetic migraine type according to the research.

This actually follows a lot of genetic research that is going on today. There are several conditions that were once thought to be a lot more clear-cut – from a few genetic factors – that we are now realizing are coming from a much more complex genetic basis.

Another interesting discovery was that different types of migraine do indeed have different – and complex – genetic backgrounds.

Don’t get the idea that we now have specific genetic profiles for every type of migraine. We’re a long way from that. What we can say, it that certain profiles do tend to mean you inherit migraine – but there are other profiles, still unknown, that may also lead to the same type of migraine.

So where does this leave us? We are finding that treating migraine, from a genetic standpoint, will rarely be a case of “altering” a gene or two, or targeting a simple function of a gene. It’s far more complex. This could mean that some treatment in the future will also need to be more complex. But there is a lot of study to be done.

If you want to get geeky and keep studying the topic, check out this article – New light on genetic foundation of migraines, and the study itself here – Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families

20 February 2015

Acetazolamide for Migraine

James Discoveries & Stats, Medications 3

Acetazolamide, sold under brand names Diamox and Diamox Sequels or as a generic drug, has attracted some attention as a migraine treatment. Is acetazolamide for migraine something that should be investigated further?

Finding treatments for migraine is very much like detective work. Finding connections, testing hypotheses, making gradual discoveries. This has been the case in the slow study of acetazolamide for migraine.

The first connection was found unexpectedly in 1978. Patients who had been misdiagnosed were given the drug, and the results were remarkably positive.

Acetazolamide became a choice drug for treating a type of ataxia which is common in familial hemiplegic migraine. This particular type of ataxia includes muscle symptoms – unsteadiness and a loss of coordination – along with vertigo and nausea. This type of migraine and these symptoms have a clear genetic connection.

Now this particular medication is far from a cure for this type of migraine; it’s usually given simply to treat the ataxia (episodic ataxia type 2). But there were some reports of improvement with other symptoms.

No one is sure why acetazolamide for migraine helps in some cases, or even why it treats ataxia. It does share at least one quality with topiramate (Topamax) – carbonic anhydrase inhibition. Topiramate is often used as a migraine preventative. And Diamox Sequels is used, like Topamax, as an anticonvulsant.

Some reports were coming in of patients with other types of migraine being helped by acetazolamide, so a trial was designed with a dose of 500mg. Unfortunately, the study could not be completed because more than a third of the patients dropped out due to side effects. Common side effects include nausea, a tingling sensation, diarrhea, drowsiness, and occasional confusion.

Although the research continues, and the drug seems to help some patients, so far it’s not looking like Diamox will be a widespread migraine treatment.

However, the connections to headache remain intriguing. For example, acetazolamide is often used to treat glaucoma, to decrease pressure in the eye. It also helps with other symptoms such as nausea, vertigo, and headache.

It also appears that acetazolamide may interrupt cortical spreading depression, a part of the migraine chain-reaction, and so interrupt migraine aura.

Although acetazolamide probably won’t be prescribed to you because of migraine, it may be prescribed for another reason. If so, watch to see if your migraine symptoms improve, and let your doctor know. Your experience may help us understand why acetazolamide helps fight migraine in some cases but not others.

Read more about acetazolamide for migraine here.

6 May 2013

What is Migraine Associated Vertigo?

James Information 2

MAV is a possible symptom of migraine disease (not a type of migraine).

Vertigo: the world is moving or spinning around you

About 25%-35% of migraineurs experience vertigo.
It’s usually accompanied by other migraine symptoms.

Patients need a proper diagnosis. Is it migraine? if so, what type?

MAV is often a symptom of:

Basilar-type Migraine
Familial Hemiplegic Migraine
Migraine with Aura

For more information:

22 May 2012

Familial Hemiplegic Migraine: Does it get worse over time?

James Discoveries & Stats 1

Many of us with migraine wonder just how much cumulative damage is taking place with such a high level of pain and other symptoms. There’s a great deal of discussion over just how migraine impacts us in the long term.

Like the rest of us, those with familial hemiplegic migraine wonder if the impact tends to get worse over time. A small study of just 6 people (one family) attempted to find out if, in this case, there was a deterioration of things such as cognitive functions and quality of life overall.

Familial Hemiplegic Migraine (FHM) is a very rare type of migraine characterized by weakness or even paralysis usually on just one side of the body.

The study tested the family of 6 and then retested them after 7 years. The study is generally good news. Although the symptoms of FHM can be pretty severe, including dysphasia (trouble understanding words) and motor weakness (muscle weakness, usually on one side of the body), and sometimes headache, the cognitive problems generally did not become worse.

On the other hand, as you may have guessed, there was not a lot of improvement either.

The only impairment that got a little worse with some people was something called visuoconstructional function. This has to do with the ability to understand spatial information and make designs – thing like copying drawings.

It should be good news to patients that disability may not get drastically worse – on the other hand, this study reminds us again that there is a lot of work to be done to better treat FHM.

via Long-term Outcome of Cognitive Functions, Emotional Behavior, and Quality of Life in a Family With Familial Hemiplegic Migraine.