Pulse
Wired Well
Pacemaker-like devices once used primarily for Parkinson's patients are now being considered for epilepsy, depression, and other conditions.
When drugs don’t work well enough for Parkinson’s disease, deep-brain stimulation (DBS) often does. Having seen the success Parkinson’s patients have had with the technology, researchers are now using and testing DBS for other conditions including dystonia, epilepsy, and psychiatric disorders.
First used in the late 1980s for patients with movement disorders, deep-brain stimulators are similar to pacemakers. They use continuous electrical impulses to stimulate targets within the brain. A battery-powered generator implanted beneath the skin in the upper part of the chest sends electrical pulses through wires that run up the side of the neck under the skin, through the skull, and deep into the brain where they connect to electrodes placed at target sites.
Patients who undergo DBS often report immediate and long-lasting relief from symptoms such as tremor and dyskinesia. “We still don’t know exactly how it works,” says University of Minnesota neurosurgeon Aviva Abosch, M.D., Ph.D., director of epilepsy, stereotactic, and functional neurosurgery. “We just know that it can be extremely beneficial to people who have movement disorders but don’t respond adequately to medication.”
When Abosch did her first DBS implants in 1999, the technology was FDA-approved only for essential tremor or Parkinsonian tremor. Now most of her patients have Parkinson’s, for which the FDA approved DBS in 2002. In 2005, it was approved for dystonia and in 2009 for obsessive compulsive disorder—the first approval for a psychiatric condition. The FDA is considering approval of DBS for epilepsy, and it’s being used off- label to treat Tourette syndrome. It’s also being tested for cluster headaches, depression, restless leg syndrome, and spasmodic dysphonia (laryngeal dystonia).
In Minnesota, most DBS surgeries are done at the University of Minnesota or Mayo Clinic. Approximately 100 procedures are performed at Mayo each year and 50 are done at the university. In recent years, Methodist Hospital in St. Louis Park, St. Joseph’s in St. Paul, and Abbott Northwestern in Minneapolis also have done a few cases.
Mayo is part of the Deep Brain Stimulation Consortium, which includes researchers from Illinois State University, the University of Memphis, and Case Western Reserve University who are working to develop a stimulator that provides feedback and regulates the release of dopamine in the brain.
Benefits Outweigh Risks
Kendall Lee, M.D., Ph.D., a neurosurgeon who heads Mayo’s Neural Engineering Laboratory, has watched Parkinson’s patients experience significant symptom relief as a result of DBS. “Some people are overcome with emotion in the operating room,” he says. “They are so joyful to have immediate relief from their symptoms.”
University of Minnesota neurologist Paul Tuite, M.D., says, “When I ask patients if they’d do it again, they respond with a definite ‘yes.’ DBS alleviates the valleys of poor mobility and the peaks of medication-induced involuntary movements.”
Despite the success stories, not all patients are candidates for DBS. To be eligible, they must not have dementia, severe untreated depression, or other significant medical problems. Patients with Parkinson’s disease must achieve at least a 30 percent improvement in motor function when on a dopaminergic medication. Such improvement supports a diagnosis of Parkinson’s disease and suggests that after DBS surgery, the patient will attain a level of function equal to preoperative levels but without dyskinesia or fluctuations in motor function.
After DBS, Parkinson’s patients usually need less medication. “Clearly it’s not a cure,” Tuite says. “We can’t prevent the remaining dopamine- producing brain cells from dying, and it doesn’t improve nonmotor symptoms of Parkinson’s such as depression or anxiety, but DBS almost always improves their day-to-day function.”
For patients with essential tremor, medications don’t work well even initially, according to Tuite. “For this reason,” he says, “you can view nearly all essential tremor patients as good candidates for DBS as long as they desire it and don’t have dementia or other medical conditions that exclude them from surgery.” He says most tremor patients are “quite pleased” with DBS as long as they don’t harbor unrealistic expectations. “We can’t always eliminate every bit of tremor, but most no longer need their tremor medications.”
Tuite says it’s hard to say if DBS outcomes are better now than they were a few years ago partly because “outcomes were pretty darn good to begin with” and partly because a few years ago, DBS was offered only to patients with advanced symptoms. Today, it’s offered within the first decade of disease before the onset of severe symptoms.
Because it’s done earlier, it’s often possible to get by with a unilateral procedure, in which an electrode is placed in the side of the brain opposite the person’s most severely affected side, instead of a bilateral procedure, in which an electrode is placed in each of the brain’s hemispheres, according to Abosch. Unilateral DBS reduces the incidence of postoperative confusion, depression, or gait disturbances—side effects that more often occur with bilateral DBS surgery. The advantage of bilateral DBS is that it usually reduces the need for medication.
Underused Approach
According to Abosch and Tuite, DBS is underused. Tuite says 30 percent to 50 percent of Parkinson’s and essential tremor patients are medically eligible for DBS. But only 10 percent of Parkinson’s patients who are eligible receive it, says Abosch, who’s conducting research to find out why. Fear of brain surgery, the high cost, and lack of access to a DBS surgical center likely prevent some from having the procedure. Insurers and Medicare generally pay for DBS for Parkinson’s, essential tremor, and dystonia, according to Tuite.
Abosch says that even though DBS was approved for obsessive-compulsive disorder last year, it’s not being used much regionally because neither Medicare nor other health plans, which tend to follow Medicare’s reimbursement lead, are paying for it. According to Abosch, Medicare has said that DBS for obsessive-compulsive disorder is “interesting, but more evidence of efficacy is needed” before the program will cover it. “It’s heartbreaking to see,” she says. “When it got approved, patients came out of the woodwork to be screened for eligibility. Medicare denies coverage. We appeal. They say no again. These people can’t function in society, and there’s no way they can pay for this themselves.”
Meanwhile, DBS technology keeps getting better. Pulse generators are getting smaller, making the implant less obvious cosmetically. A new generation of rechargeable batteries now lasts seven to nine years, instead of three to five years. The connection between the electrode and the extension cable that runs down the neck is smaller, which makes it less likely to erode the skin and cause infection. Programming precision has improved, too. And the FDA has approved new electrodes specifically designed for DBS. (Medtronic still makes the only FDA-approved stimulator systems, Abosch says.)
In addition, better MRI imaging and new contrast agents have improved visibility within the brain. “We can create better brain maps and improve placement of electrodes,” says Kevin Bennet, a chemical engineer who chairs Mayo’s division of engineering. Electrode placement and pulse-generator programming are still fine-tuned by observing the patients and listening to their comments about how and what they feel. ABC News recently featured Minnesota Orchestra associate concertmaster Roger Frisch, who has an essential tremor, playing his violin while Mayo neurosurgeons positioned the electrode in his brain. Every note he played told the surgeons whether the electronic pulses coming from the electrode were easing his tremor.
To further improve programming precision, Mayo is developing an “accelerometer” that quantifies tremor strength. “It will provide additional information for precise programming, which will improve patient outcomes,” Bennet says.
Meanwhile, St. Jude Medical in St. Paul has two deep-brain stimulation systems approved and used in Europe. U.S. clinical trials for both devices, including the Brio, the world’s smallest rechargeable DBS device, are well underway.
Mayo is also working on a device that measures the effect DBS has on the release of neurotransmitters in the brain. The Wireless Instantaneous Neurotransmitter Concentration System is able to sense real-time levels of dopamine, serotonin, adenosine, glutamate, and norepinephrine, according to Lee, who is working with Bennet and others to miniaturize the device so that the pulse generator, battery, and circuit chip can be embedded in the skull. “We still have a lot of work to do,” he says. “FDA approval is a few years away.”
Researchers from Mayo and the University of Minnesota foresee the day when DBS will treat a variety of conditions beyond movement disorders. And until a better therapy for Parkinson’s comes along, Tuite says, “DBS offers a second life to people who are not sufficiently managed with medications.”—Howard Bell