Trembling, twitching, cramps – for those who suffer from movement disorders, sometimes just stepping outside their homes can turn into a gauntlet run. They have to endure the quizzical stares of fellow human beings, and they are often marginalized. A research association at Charité – Universitätsmedizin Berlin is exploring the causes of movement disorders under the supervision of Andrea Kühn, a professor of neurology. Experts and expertise from various disciplines are being brought together in a new section to examine the interrelationships and to develop new, customized therapies.

Parkinson’s Goes Hand in Hand with a Great Deal of Suffering

Parkinson’s is one of the most common triggers of movement disorders. According to the Deutsche Parkinson Gesellschaft, currently more than 250,000 people in Germany are afflicted. Andrea Kühn, who heads the Movement Disorders unit at the Charité-Mitte campus, explains that “Parkinson’s is a neurodegenerative disease in which nerve cells of the midbrain, which are responsible for producing the neurotransmitter dopamine, inexplicably die off.”

“Parkinson’s patients commonly lose their ability to control their movements and become immobile; they feel frozen in place.” This is caused by the brain no longer producing enough dopamine – a neurotransmitter that, among other things, acts as a stimulus. “Then again, medications that are prescribed to treat Parkinson’s patients often lead to hyperkinesia, leaving those affected unable to properly coordinate their movements,” says Kühn. This disease goes hand in hand with a lot of suffering. “In many cases, Parkinson’s patients are stigmatized because their behavior attracts attention, and they are looked upon with skepticism. Many sufferers choose to withdraw from the public view completely.”

Next to Parkinson’s, there is a whole series of other diseases that can engender movement disorders. “Relatively frequently you see this with dystonias, in other words “cramps,” or with essential tremor, a shaking of the hands when moving. Occasionally this shaking affects the head or the voice,” Kühn suggests. “Here the causal links are still much more inconclusive than with Parkinson’s disease.” What all these ailments have in common, however, is that they are so-called “neural network” diseases. “The various regions of the brain communicate with the help of electrical signals that transmit nerve impulses with rhythmic oscillations. In the case of movement disorders this transmission of information is impaired. Especially the communication between the cerebral cortex and basal ganglia – the pit-like structure below the cerebral cortex – no longer functions as it should.”

Alleviating Symptoms with Electro Stimulation

Exactly how the networks in question communicate with one another – and what type of patterns result – is what Kühl and her team are exploring jointly with neurologists, neurophysiologists, psychiatrists, and neurosurgeons at Charité – Universitätsmedizin. “Brain cells send their signals and oscillate together in rhythms. Depending on the disease, the rhythm in certain regions of the brain can be either too slow or too synchronous.” By measuring brain waves, scientists can determine the patterns with which various regions of a patient’s brain transmit signals. With the help of electrical stimulation it becomes possible to “over-write” pathological rhythms and thereby alleviate a patient’s symptoms, Kühn explains.

“This is where a so-called brain pacemaker comes into play – a device that continually sends impulses.” Deep brain stimulation (DBS), as this procedure is known, is already being offered at the Movement Disorders and Neuromodulation Section today. About 50 such surgical procedures are carried out by Andrea Kühn, her team, and doctors at Charité each year – generally on Parkinson’s patients. “A small hole is drilled into the patient’s skull through which the neurosurgeon inserts a micro electrode into the brain. All the while, we measure the brain activity to find out at which precise spot the electrode should be permanently placed,” Kühn explains. “Patients are awake during this operation so that we can instantly test the stimulation effects.”

Once the electrode is positioned in the right spot, a small battery-operated stimulator about the side of a child’s palm is inserted laterally below the patient’s sternum. The stimulator is connected via a cable to the electrode in the brain, which constantly sends out high-frequency signals at 130 Hertz and thus “over-writes” the erroneous communication pattern of the diseased brain region.

An Evening at the Philharmonic Concert Hall with a Brain Pacemaker

Unlike heart pacemakers, deep brain stimulation devices are not yet advanced enough to send signals as needed. “Nowadays cardiac pacemakers are generally responsive – or adaptive. In other words, they measure whether the heartbeat is irregular and they only emit a signal if needed. We haven’t gotten to that point yet with deep brain stimulators,” Kühn declares. In the future, the brain pacemaker will also function adaptively. “One of our goals is to get better feedback on the activity of an impaired brain region so that the pacemaker can be engineered to react only as necessary.” But even today this procedure, which was first introduced 25 years ago, and which has been decisively refined since then, allows us to vastly improve the situation of our patients, says Kühn. “There’s one particular patient who really sticks in my mind, a 74-year-old Berlin Philharmonic Orchestra enthusiast. Her tremor was so bad that she was unable to hold her feet still during a concert.” The awkwardness brought on by her involuntary movements – along with the noise these caused – left her not wanting to leave her home for the most part. “After the deep brain stimulation procedure, she was able to enjoy concerts again,” a delighted Kühn adds.

The objective of scientists is to better understand how movement disorders develop so they can intervene as soon as possible. Kühn and her colleagues are banking on an interdisciplinary exchange of ideas and even closer collaboration among basic researchers, clinicians, and clinical neurophysiologists to meet this objective. An interdisciplinary approach and the transfer of scientific findings from basic research to clinical application is also the focus of Charité’s NeuroCure Cluster of Excellence, on whose board Andrea Kuhn is a memeber.  “Among other things, we work together with the Bernstein Center for Computational Neuroscience, which designs computer models of neuronal circuits and provides valuable help in understanding neural networks,” says Andrea Kühn. “Our dream, of course, is to one day understand the development of these diseases well enough to be able to intervene even before a communication disorder can take hold in the brain.”