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Magnetic help for the brain

Treating stroke patients with magnetic fields has proven itself in research as transcranial magnetic stimulation. Scientists from Jülich and Cologne are testing this method in a large clinical study – the first of its kind worldwide. Their long-term goal is individualised therapies.

All of a sudden, Wilhelm Zeffler can no longer move his left leg and left arm. The 74-year-old is crawling down the corridor towards the telephone when, fortunately, his wife comes home and immediately calls the ambulance. Things go very fast then: ambulance with flashing lights, paramedics and physicians in action. The preliminary diagnosis is: stroke. This means that parts of the brain are no longer supplied with blood and nerve cells die. "Time is brain" is the slogan, because the sooner the patient is treated, the greater the chance of minimizing subsequent damage. The pensioner, who had been fit up to then, is transferred to the stroke unit – the special organisational unit within a hospital that takes over the initial treatment of stroke patients.

Wilhelm Zeffler is one of around 270,000 people in Germany who suffer a stroke every year – this means that one person is affected every two minutes. 63,000 men and women die as a result. Stroke is the fourth most frequent cause of death in Germany after heart disease, cancer and lung disease.

"The topic is affecting more and more people, because our population is ageing and so the number of stroke patients will continue to rise," says Prof. Christian Grefkes (photo). After completing his medical studies, the 41-year-old specialised in strokes. Since 2005, in close cooperation with his long-time mentor Prof. Gereon Fink, he has been working and conducting research on transcranial magnetic stimulation (TMS) at the Institute of Neuroscience and Medicine (INM-3) and at the University Hospital Cologne. With TMS, specific areas of the brain can be painlessly impacted from the outside via a magnet coil. Grefke’s research and scientific commitment have already won him several prizes, including the Young Investigator Award of the Competence Network Stroke. In the competition "Germany – Land of Ideas", his topic "Early Rehabilitation of Stroke Patients through Brain Stimulation" was distinguished as a "Selected Landmark".

Christian Grefkes und eine Kollegin demonstrieren die transkranielle Hirnstimulation an der Uniklinik Köln.Christian Grefkes has specialised in strokes. He conducts research on transcranial magnetic stimulation (TMS) at the Institute of Neuroscience and Medicine (INM-3) and at the University Hospital Cologne.
Copyright: Universitätsklinik Köln / Christian Wittke

"This topic already fascinated me during my studies and has kept preying on my mind ever since. And in recent years, we have also achieved some breakthroughs," says Grefkes. In 2007, for example, in the first major study involving stroke patients, Jülich researchers found out how the brain recovers and reorganises after a stroke. It had already been known that in a stroke, a part of the brain is no longer sufficiently supplied with blood and brain tissue dies. Depending on the severity of the stroke, the physical consequences are paralysis, impaired balance and visual or speech disorders. Over time, other healthy areas of the brain take over the tasks of the dead regions. "Our study results were a surprise," says Grefkes, looking back. The Jülich scientists could show that in some stroke patients, the healthy half of the brain does not support the damaged brain region during the reorganisation, but – on the contrary – inhibits it.

“With the help of transcranial magnetic stimulation, we were able to suppress the disruptive action of the healthy half of the brain for a short time – with the result that the affected patients could employ the use of their hands again for a deliberate purpose. In plain language: by specifically inhibiting excessive brain activity and the resulting normalisation of the networks, we achieved a motoric improvement – this was a completely new discovery,” says the physician. This also revealed that there is no single optimal solution to improve motor functions after a stroke. Researchers have to take a very close look at the condition of the brain in order to remedy the disorder in the network in the long term with a therapy tailored to the patient.

Directly at the bedside

To detect the disorder, researchers have so far mainly used functional magnetic resonance imaging (fMRI) as an imaging method. It makes active regions in the brain visible in three dimensions. The patients are placed in a narrow tube in which they lie absolutely still and breathe evenly so that the imaging is not disturbed. "However, the examination is too time-consuming for everyday clinical practice and not all of those affected manage to remain calm or to follow the respective instructions," says Grefkes.

In future, a new method that doctors can use directly at the bedside without great effort will provide a way out: a combination of TMS and electroencephalography, a measurement of brain waves better known under the abbreviation EEG. The Jülich and Cologne researchers are currently testing their approach in an experimental study. "By combining EEG and TMS, we are able to measure directly how stimulation by magnetic fields affects the brain. This allows us to adapt them to the needs of the patients – a tailor-made stimulation, so to speak. Although this is still up in the air, it is almost within reach," says Grefkes.

While this may not sound particularly impressive to the layman, it requires a lot of skill and even more mathematical understanding because TMS and EEG react to each other like fire and ice. "EEG is a method of measuring very fine nerve currents; in contrast, magnetic stimulation is so strong that it initially interferes with every signal that the EEG records," explains Prof. Silvia Daun, a mathematician from Jülich and also from INM-3. Nevertheless, with a focus on stroke patients, the researchers have succeeded in combining the two methods.

Silvia DaunThe mathematician Silvia Daun has specialised in biological processes. She develops models for stroke research that show how magnetic stimulation impacts the brain of patients.
Copyright: Forschungszentrum Jülich / Sascha Kreklau

This parallelism of stimulation and effect is still new territory in stroke research. Scientists hope to gain new insights and prediction models from this based on the mathematical network models developed by Silvia Daun. "The EEG helps us to see where the network disturbance is in the system, where we have to intervene with magnetic stimulation and which network node we have to strengthen or weaken with stimulation in order to support the recovery of the brain – that is hot news," says the scientist.

Concurrently, the researchers led by Fink and Grefkes are involved in a study on TMS as a therapy for stroke patients, the only study of its kind in the world to date. It includes 150 women and men. In a previous feasibility study, they were able to show in 26 patients that TMS can improve motor function in the first two weeks after a stroke. The researchers had additionally stimulated the brain region that is responsible
for movement. "The networking of brain areas improved due to stimulation. And it is precisely this networking that is considered one of the most important factors for the brain to recover," said Grefkes.

This very complex clinical study has been running for two years and is expected to take another two years. "If we succeed in repeating the success of the feasibility study in the large group," says the physician, "we would have the first truly well-tested therapy that complements the current rehabilitation methods with a completely new approach."

Katja Lüers

This article is published in the magazin effzett (1/2008).