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Better understand cerebral hemorrhage in women

Women are twice as likely to suffer a cerebral hemorrhage than men. Dr. Ynte Ruigrok is determined to understand why. Her multidisciplinary approach includes analyses of DNA and brain scans, and research on hormones, lifestyle and risk factors. Here’s how Ynte’s innovative research can lead to early detection and prevention of this life-threatening condition.

Introduction

Ynte Ruigrok is a vascular neurologist and associate professor at UMC Utrecht. “Vascular means that within neurology, the study of brain diseases, I have particular knowledge of the blood vessel system in the brain and the diseases that can arise there,” she explains with a modest smile.

Last December, Ynte received a Dekker Scholarship from the Heart Foundation. With this grant, she is conducting research into cerebral vascular hemorrhages and how it is that especially women get cerebral vascular hemorrhages. The UMC Utrecht recently appointed Ynte as a clinical scientist. “This appointment allows me to continue my research, in addition to my work as a doctor,” she said.

You do research on cerebral hemorrhages in women. Why?

“Two out of three people who suffer a cerebral hemorrhage are women. I would like to know why this is more common in women than in men. After all, a cerebral hemorrhage is a very serious disease. Half of the people who get it are younger than 50, are in the middle of life and often still have children living at home. After the hemorrhage, the patient has a one-third chance of death and a one-third chance of life-long serious disability. Those numbers worry me quite a bit. With my research, I want to achieve that fewer people and therefore especially women get cerebral hemorrhage.”

How does a meningeal hemorrhage actually occur?

“A cerebral hemorrhage occurs when an aneurysm in the brain ruptures. Let me explain that! An aneurysm is a bulge of a large blood vessel (an artery) it is shaped like a balloon. The wall of an aneurysm is less sturdy and may eventually burst open. Then there is a meningeal hemorrhage: a large amount of blood gets between the meninges, often with serious consequences.

Most people who have a brain aneurysm do not know it themselves. After all, it doesn’t cause any symptoms. You can only find out when it bursts open and causes a meningeal hemorrhage. And so by then it’s actually too late.”

Facts and figures about meningeal hemorrhage and aneurysm

  • 3 in 100 Dutch people have an aneurysm in the brain, without knowing it themselves.
  • 2 in 3 people with a brain aneurysm are women.
  • In 2 in 100 people with a brain aneurysm, the bulge will at some point burst and cause a cerebral hemorrhage. That’s about 1,500 patients in the Netherlands each year.
    Of those 1,500 people:

    • 1 in 3 die within 3 months of the meningeal hemorrhage.
    • Does 1 in 3 develop a lifelong severe disability.
    • Does 1 in 3 have no serious complications, but usually cannot function at the same level as before the hemorrhage.
  • Also 2 out of 3 people with cerebral hemorrhage are women.
  • That means women are 2 times more likely to have a brain aneurysm and cerebral hemorrhage than men.

How do you research that?

“I want to find out the causes that make the disease more common in women. This will give us a better picture of the risk factors in women as well as in men. For this I look at several things: DNA and genes, the lifestyle of the patients, the size and shape of brain blood vessels and the influence of hormones. I want to combine all this information into a risk model that estimates how likely it is that someone will develop an aneurysm. Actually, this will be two risk models: one for men and one for women. The risk model for women may then include other predictors, based on the risk factors research we are doing now.”

Ynte's research on the risk factors of cerebral aneurysm

DNA and genes

In some diseases, the cause is an error (mutation) in a single gene, but not in brain aneurysm. There are many genes that all play a small role. To study that properly, you need the DNA of lots of people. In collaboration with colleagues from home and abroad, Ynte has set up a database containing the DNA of 10,000 people. These are both patients with brain aneurysms and healthy people. This allows them to unravel the various genes involved. Together with colleagues, Ynte is expanding this database and will soon contain the DNA of as many as 30,000 people.

Imaging the brain vessels

Ynte’s research group has made many brain scans of people with an aneurysm. On these scans, the blood vessels can be clearly seen. With this, they have developed a software program that measures how narrow or wide a blood vessel is, or how sharp the bends between splitting blood vessels are. It is known that a narrow or unsegmented blood vessel and a sharp bend between blood vessels are more likely to cause an aneurysm. Ynte will now investigate whether these characteristics are more common in women than in men.

The role of hormones

Ynte thinks hormones also play a role in the development of aneurysms. These are mainly sex hormones, and they are different in women than in men. But the research so far gives contradictory results: one study shows that certain hormones increase the risk of an aneurysm, another can find no connection. According to Ynte, this is due to too small patient groups in previous studies. She wants to investigate this herself with a larger number of patients.

Lifestyle and environmental factors

It is known that high blood pressure, smoking and drinking a lot of alcohol increase the risk of a brain aneurysm. But we do not yet know whether these risk factors play as big a role in women as in men. And perhaps there are lifestyle issues that play a role only in women. Ynte would like to find out these risk factors so that she can predict as accurately as possible which people have a high risk of cerebral artery hemorrhage.

What can you do with such a risk model?

“With this, we can determine which women and men are at high risk for an aneurysm. In the future, general practitioners can fill out this model, and refer those people to the hospital for a scan. If someone is found to have an aneurysm, the doctor can close it with surgery so that it cannot burst open again. That way we can minimize the chance of a cerebral hemorrhage. Currently, doctors are already examining family members of people who have had a meningeal hemorrhage to see if they also have an aneurysm. With our risk models, we will soon be able to detect other people with high-risk aneurysms early as well.”

Surgically closing an aneurysm sounds like a hefty procedure. Are there other treatments available?

“That is indeed true, it is quite an invasive procedure. When we find an aneurysm, we always discuss with the patient the advantages of the procedure, preventing bleeding, and the disadvantages. After all, any surgery presents a risk of complications. Currently, there are no other treatments against a brain aneurysm. But it would be so wonderful if, in addition to this surgery, we could have a drug that could inhibit the growth of an aneurysm. Thinking a little further, I would like to offer people with a high risk of aneurysm already preventively such a drug. Maybe then the aneurysm won’t develop. This is really still in the future, though.”

People behind the story

Ruigrok

Full Professor

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