hypothalamus

24 November 2020

Emerging Treatments and Sleep

Research from the past few years had led to a sudden influx of new pills and injections for migraine, with many more under investigation. But there could be an interesting connection between some of these treatments – your body’s regulation of sleep patterns.

Anyone with migraine will immediately know the connection if we say the words “sleep” and “light”. Sleep is a classic “abortive treatment” for migraine. Changes in sleep schedule are a classic trigger. For many, light patterns and flashes may trigger an attack – and once an attack starts, bright light is the last thing you want!

All this is related to your body’s “clock”. Except that it’s not really that simple. Although you could say that there’s a “master clock” in the hypothalamus, there are also many individual clocks. Some are trying to “sync” with their environment (light plays a big role in this). Others seem to have a mind of their own.

We usually think of the 24 hour clocks, but there are also yearly (circannual) cycles. Cluster headache patients are especially aware of certain rhythms that help explain the “clusters” of these terrible headaches.

Not only are we just beginning to understand how the body regulates all these things, we are really just starting to study these rhythms in migraine patients (and we have a lot to learn about cluster as well). So we have a very long way to go!

But Dr. Philip Holland of King’s College London is a lead researcher who is noticing an interesting connection between the body’s clocks and recent research into migraine treatments.

If you’ve been watching the news, you know that drugs acting on CGRP (calcitonin gene-related peptide – a peptide which occurs naturally in the body and is linked to the migraine chain-reaction) are all the rage. You may also know that there are many upcoming treatments targeting PACAP (pituitary adenylate cyclase-activating polypeptide) are being researched.

So – more drugs and injections. But one thing that CGRP and PACAP have in common is that they’re related to sleep regulation. PACAP works with light to help the function of the hypothalamus clock.

What if sleep patterns could tell us which drugs would work the best? Or what if, instead of developing new drugs, we could find natural ways using light and sleep schedules to minimize or eliminate migraine and cluster headache?

Of course, as we know, these behaviours are already being studied and used to fight headache. What’s new is that we’re starting to see how sleep/wake schedules work in the chemistry of the body. But emerging research is perhaps pointing to the fact that we need to pay more attention to light (think especially of how we use screens, or how working “by the clock” instead of “by the sun” effects us) and our sleep patterns.

By the way, we mentioned Dr. Holland. He is a runner-up in this year’s Medical Research Foundation Emerging Leaders Prize. Read more about the research he is doing at the link above, or at The Migraine Trust here. One of his recent papers can be accessed here: PACAP in hypothalamic regulation of sleep and circadian rhythm: importance for headache (pdf).

9 January 2017

Cluster Headaches Causes

James Information, Uncategorized 1

As with any type of pain, the agony of this super-intense headache raises the question – what exactly are cluster headaches causes? In other words, why am I in such incredible pain?

There are actually two questions to ask. First, what may actually trigger a cluster headache attack at a certain time? But the other question is – why is it that a certain trigger results in a headache for one person, but not another? In other words, what is the cause of the disease in the first place?

But before we get into cluster headaches causes, make sure you understand what cluster is. Here is a handy infographic contrasting migraine with cluster: cluster headache vs migraine

So why does one person get cluster headache attacks, while another person doesn’t?

There has been some research done into the possibility of a genetic cause, or at least genetic factors that contribute. For many years now, researchers have recognized that family members of a cluster patient are more likely to have cluster themselves. In late 2016, a study from Italy was published in the Journal of Headache and Pain, indicating some possible genetic variants that seem to increase a patient’s risk (A genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variants.).

Most often when we talk about cluster headaches causes, we end up discussing the brain and nervous system. We know, through modern imagine techniques, that the hypothalamus is involved, as has long been suspected. The trigeminal nerve in the head seems to be important, especially in the process that causes symptoms such as eye pain, tears and congestion. Other possible indirect cluster headache causes are related to a nerve cluster behind the nose (the sphenopalatine ganglion), histamine, and the blood vessels themselves. Read more about these factors here: What is behind the dreaded Cluster Headache?

All that being said, there is still nothing we can point to with certainty. Cluster may indeed be caused by a number of factors working together – for example, even someone who is predisposed genetically may not get cluster because other physical factors are lacking. There are other behavioural factors, such as a history of smoking, which seem to play a role.

But what actually kicks off a cluster headache attack (or, what triggers a cluster period)?

Cluster isn’t as closely connected to “triggers”, such as food or hormonal changes, as migraine is. There are some factors which have been related to periods of cluster headache attacks, including smoking, sleep apnea, and the season of the year (autumn being the highest risk time of year).

Once the cycle has started, there may be other individual cluster headache causes. Alcohol is commonly reported, as well as strong chemical fumes. A hot day, or getting “overheated” during exercise seems to trigger attacks for some. However, when you’re not in a “cluster period”, these things will not trigger attacks at all.

Cluster is hard to research because it is so rare. However, we are learning more and more about the brain, and the last 30 years has brought us incredible advances in understanding. Many of these new revelations about cluster headache causes have brought new treatments to the forefront, such as deep brain stimulation for chronic cluster headache patients.

Further reading: Cluster headaches causes and treatments (Medical News Today)

15 November 2013

Are Migraine Researchers Preoccupied with Pain?

James Discoveries & Stats 13

There’s no doubt that, for most people with migraine, pain is a big concern. But the truth is, pain is not the only symptom of migraine. And it could be that our focus on pain is hindering research.

Dr. Peter Goadsby of the University of California San Francisco Medical Center, is one of the researchers who is concerned that too many are focused on pain, thinking that the pain of migraine is simply causing other symptoms.

Of course, many migraine sufferers will realize that this idea is suspect. After all, what about the symptoms that typically appear before the pain?

But another question is, what about the symptoms that often go with the pain? Is pain simply causing nausea, or is the nausea simply caused by an underlying problem? What about the feeling of heaviness some patients describe, or sensitivity to light?

There is a lingering supposition that pain is simply causing problems in the head – changes in blood vessels, for example. But if there’s an underlying condition of the brain that leads to most migraine symptoms – we must find a treatment for that condition.

Dr. Goadsby’s Study: A Disorder of the Brain

In a study presented earlier this year, Dr. Goadsby believes he has confirmed yet again that migraine symptoms come from a disorder of the brain. In his words:

This is an important step in solidifying our ideas that migraine is fundamentally a disorder of the brain, not a disorder of structures outside the brain. We were able to address the question that people have wondered about for many, many years, that is, what is the degree to which pain is driving the initial symptomatology â€” and we got clear answers to that.

The study used brain scans, but did something that is rare in migraine research. Brains were scanned before the headache hit. This allowed researchers to study migraine symptoms that were present before there was any pain.

So were there changes in the brain before headache? You guessed it – the answer is yes. And we have been able to get a glimpse into which parts of the brain change in the “early stages” of an attack.

For example, the hypothalamus. Just above the brainstem, the hypothalamus is known to be key in cluster headache. It’s key for functions like sleep and mood.

The midbrain was also involved, confirming earlier studies.

The visual cortex was active in patients with visual problems. And the medulla in the brainstem was active in patients experiencing nausea.

This may all seem rather obvious, but the key here is that these patients had not yet experienced migraine headache. So in the case of nausea, for example, it could be that it’s not dependent on the pain, but simply another result of the changes in the brain that cause migraine. Dr. Goadsby explains:

…it’s entirely plausible that those areas are activated by the migraine process and that’s why nausea and vomiting are so common in migraine; it’s not simply a response to the pain … It was thought that nausea and pain were highly linked, but that doesn’t seem to necessarily be the case.

A New Research Manifesto?

Treating symptoms is very important – but we want a cure to migraine – a cure that will end all migraine symptoms.

Research and treatment need to be dealing with the brain. The other symptoms of migraine need to be taken seriously, so that we’re not just stopping pain (often that approach doesn’t work anyway), but stopping migraine.

Patients also need to be cautious of “treating pain” with “painkillers”, and instead look to a complete and targeted migraine treatment plan.

Dr. Goadsby hopes that there will be a shift in thinking when it comes to migraine. “From a big picture treatment perspective, this says to me that we probably won’t get away with developing drugs that don’t get into the brain to have substantial effects on migraine prevention”.

What is behind the dreaded Cluster Headache?

James Information 7

Just what causes one person to be a cluster headache sufferer? As with many headache disorders, the cause of cluster headache is not completely understood. But we are getting closer.

So here’s the question – what parts of the body are involved in the cluster attack? And how are they involved?

1. The hypothalamus: The hypothalamus is now thought to be the launching pad of the cluster attack. It first becomes a suspect because it controls your 24 hour clock. Cluster is a very regular disorder, in that it comes in cycles (hence the name – cluster).

About the size of a almond, the hypothalamus is found right above the brain stem. Thanks to modern imaging techniques, we can see differences in the brain of a cluster headache sufferer.

2. The trigeminal nerve: Parts of the trigeminal nerve are activated during a cluster attack. This is a very important nerve in your face and jaw. It’s involved in the eye pain, tearing and redness of cluster. It can also help bring on the congestion.

3. The sphenopalatine ganglion: A “ganglion” is a group of nerve cells. This particular ganglion is located behind the nose. Some cluster patients have found relief after surgery on the sphenopalatine ganglion.

4. Blood vessels: Changes in blood flow may be involved in cluster, but we know now it’s not as central as we once thought. There can be changes in blood flow, but the question is whether or not this is a result of an attack or a part of the cause.

5. Histamine: Histamine has been a suspect because you can sometimes trigger an attack with histamine. However, so far research has not been convincing.

We’re learning more and more about just how the hypothalamus is activating during a cluster attack. Thanks to modern imaging and analyzing techniques (such as voxel based morphometry), we can see more of what goes on during an attack. This has led to better treatments, but we still have a long way to go.

21 July 2010

Deep Brain Stimulation is helping Chronic Cluster Patients

James Treatments 4

Deep Brain Stimulation (DBS) is a treatment that is showing great promise when it comes to treating cluster. Unfortunately, many people know very little about it.

Deep Brain Stimulation for Cluster Headache

DBS is probably most well known as a treatment for Parkinson’s disease, though it’s used for a variety of conditions, including cluster headache.

Though much of the mechanism of cluster remains a mystery, we do know that the posterior hypothalamus is involved. The posterior hypothalamus is part of the hypothalamus part of your brain, located just above the brain stem. Like migraine, there is likely a complex web of reactions going on that impact cluster. However, the posterior hypothalamus seems to be a key part of the process.

So what would happen if we could stimulate this part of the brain directly?

DBS uses a battery operated device known as a neurostimulator. This small device is surgically implanted. It’s then able to target the posterior hypothalamus and deliver electric stimulation.

The neurostimulator itself is not in contact with the target area. Instead, a lead/electrode wire is placed in the target area. Then an extension connects the lead to the neurostimulator itself. Multiple leads may be implanted in target areas.

Once the system is in place, it can be adjusted without further surgery.

Who is this treatment for? The best candidate for deep brain stimulation is someone with chronic cluster headache. In fact, it’s been suggested that even stricter criteria be used: patients who are the best candidates are ones who have attacks almost every day. Also, these patients are usually not helped by the standard drug treatments.

Recently, researchers have started investigating the uses of DBS in other parts of the brain, such as the midbrain tegmentum. We may find that some patients respond better to stimulation in one area, and others improve with stimulation in another area.

The good and the bad of deep brain stimulation for cluster…

The good news is that the surgery is generally safe. However, that does come with a word of caution. It’s important to have an expert team perform the surgery – if possible, someone with experience with DBS for cluster, since there are unique challenges for cluster patients. The patient needs to be monitored to avoid problems such as bleeding and infection and issues with wire placement. Usually these are not major problems, and treatment can be continued. But you do need an expert who knows how to deal with them.

It’s also important to realize that improvement is not immediate. Usually several weeks of stimulation are required before there is a real change.

The other challenge with DBS is that it’s still relatively new. Yes, we have about 10 years of experience using it for cluster. But chronic cluster is so rare that we’re still only talking about a few dozen patients. More studies need to be done to understand how best to use DBS.

DBS seems to help about 60% of chronic cluster patients. The good news is that those 60% end up almost pain-free. And this is without drugs, which means a lower overall cost as well.

For more details on the use of DBS for cluster, read: Deep brain stimulation in trigeminal autonomic cephalalgias. (2010 overview) and DEEP BRAIN STIMULATION TREATMENT FOR CLUSTER HEADACHE (more in-depth overview from 2005).

Also check out Cluster or Migraine: What’s the Difference?