It is easy to be convinced that deep brain stimulation (DBS) works to improve Tourette syndrome. Just watch Jamie Furlonger before and after his DBS operation. His vocal and motor tics seem to disappear as the stimulation is turned on. Is this a "miracle," as it was described by reporters?
“The trap that the medical community and the press can fall into is conveying a false message that DBS is a cure for Tourette syndrome, or that we really understand it well at this point,” says Paul Larson, a neurosurgeon at the University of California Medical Center who specializes in the surgical treatment of movement disorders.
It is still not known how DBS works. Despite this, the surgery has been used to treat tens of thousands of people with Parkinson’s disease, for whom the treatment is approved by the FDA, and around 100 people with Tourette syndrome, for whom the treatment is considered experimental. Neurologists think that DBS could work on people with Tourette’s by disrupting overactivity in deep-brain structures called the basal ganglia. When stimulated, several different areas within the basal ganglia seem to reduce tics.
Tourette syndrome is an inherited neurodevelopmental disorder that starts in childhood. Symptoms, including involuntary motor and vocal tics, are at their worst in the early teens, typically subsiding in late adolescence or early twenties. However, some people with Tourette’s find their tics do not improve even with medication or behavioral therapies. This second group may seek surgery such as DBS.
The operation to install DBS involves implanting electrodes in the brain and a battery pack in the chest, and then wiring the two together. It takes about three hours to complete the surgery, according to Domenico Servello, a neurosurgeon who works with a specialist Tourette syndrome centre in Milan. His group has carried out 42 DBS operations on people with Tourette’s.
The tentative view of neurologists and neurosurgeons is that DBS is a "promising" treatment for people with severe and intractable Tourette’s. In the past decade, there have been about 40 cases recorded in scientific studies, which have reported improvements of varying degrees; it is not known whether the 60 or so unreported cases were as successful.
The largest study so far, published in 2008, involves 18 people treated by Servello’s group in Milan, some of who undergo an "on-off" pattern to their treatment, and some a "sham off" to test whether it's the stimulation that is effective or just the idea of the stimulation. That study concludes that DBS is a safe and useful treatment for people with Tourette’s, that some people respond better than others, and the majority still need to take medication at a reduced dosage.
“We presume that the risks of things like infection, stroke, hemorrhage, would be no higher and maybe less in young adults with Tourette's syndrome than in older adults with Parkinson’s disease,” says Jonathan Mink, a professor of neurology at the University of Rochester and scientific advisor to the U.S. Tourette Syndrome Association (TSA).
But infections and device rejection appear to be more common among people with Tourette Syndome compared to people with disorders such as Parkinson’s. This leads Servello to speculate that Tourette’s also somehow involves the immune system. Another factor in the increased risk of infections could be that obsessive compulsive disorder is frequently associated with Tourette’s— and repeated touching of the surgical scar can cause infection.
To be sure DBS is a safe and effective treatment for Tourette's, researchers need to do more testing on far greater numbers of people. In addition, more needs to be known about the effects of stimulating the medial thalamus, the site uniquely and most commonly targeted in DBS for Tourette's. This area was not investigated in the large body of research into Parkinson's.
The TSA is setting up an international registry to collect results from around the world. The association and researchers hope the shared information will shed light on the circumstances of successful operations and steer the course of future research.
“Perhaps the biggest challenge for DBS in Tourette's is what brain target people should be using and studying. There are multiple targets that appear to show efficacy,” says Larson, who authored a 2008 paper on the challenges of treating psychiatric disorders with DBS.
Besides the medial thalamus, there are around nine sites with potential for further exploration, including the globus pallidus and the internal capsule. “It is hard for me to say which target is the best because we have to study each target properly to say with it is good or not – we started with the thalamus,” says Linda Ackermans, a surgical resident studying Tourette's surgeries at the department of neurosurgery at Maastricht University Hospital in the Netherlands.
The 2011 study she participated in, published in Brain, was a double-blind randomized off-on trial in six patients who had an electrode placed in the thalamus. Ackermans says: “After thalamic stimulation, you have a tic reduction of 30 to 40 per cent.”
Will targeting different areas of the brain affect different symptoms of Tourette syndrome, or associated mood or behavior disorders? A 2009 follow-up study by Servello and his colleagues, led this time by Mauro Porta, suggests that for some patients stimulation of the thalamus reduces the symptoms of obsessive-compulsive behavior along with the tics.
The Milan group also has been targeting different parts of the brain that it thinks will treat not only tics but also associated disorders. “We use three different targets depending on the phenomenology of the syndrome,” Servello says. For instance, seven people with Tourette’s and significant OCD had electrodes implanted in the nucleus accumbens and the internal capsule.
But the treatment of Tourettes and mood disorders is a complex issue. “We want to make sure that the subject’s disability was due to their tics rather than a personality disorder or depression,” Mink says. His group’s 2006 recommendations for who might have the surgery set the bar high to make sure people try a range of medications and behavioral therapies before considering surgery. Since then, the first large-scale trial of comprehensive behavioral intervention for tics has been published. The study shows the therapy reduces symptom severity on a par with medication.
The age conundrum
The most controversial part of Mink’s group’s recommendations, however, was suggesting a minimum age of 25 for people to try DBS to treat their Tourette’s symptoms. His group was in “complete consensus,” he says, about this, because Tourette’s is not a degenerative disease and about one-third of severe children become completely symptom-free as adults. “We wanted to make sure that even though the risk is low, we weren’t recommending a procedure that has some risk of mortality to individuals who were likely to get better anyhow,” he says.
Servello disagrees. “Sometimes 25 is too late. There are a lot of exceptions, for example, malignant Tourette’s, where patients get cervical myelopathy due to tics. And patients who self-injure risk losing their vision or their hearing because they continually hit their eyes or ears,” Servello says, “The peak of the syndrome is about 14 or 15 years old. This is a crucial period in the life of a person. If you intervene too late you risk that they can’t have an education, find a job or find a partner.”