Summer 2011

Deep Brain Stimulation — Treatment Offers a Reprieve for Some Parkinson’s Disease Patients

By Maura Keller
Aging Well
Vol. 4 No. 3 P. 10

Deep brain stimulation can alter the abnormal function of the targeted brain structure in Parkinson’s patients.

Parkinson’s disease (PD) is a debilitating degenerative disorder that begins slowly and worsens as the damage to brain cells continues, leaving patients with loss of muscle control, impaired gait, shaking, and stiffness. But thanks to deep brain stimulation (DBS), in which an electrical stimulation device is implanted in the brain and programmed remotely, more patients can control these symptoms for an improved quality of life.

At Its Core
DBS is a technique that has been available for treating neurological disorders since the 1970s. According to Antonio De Salles, MD, PhD, a professor of neurosurgery and radiation oncology and head of the stereotactic surgery section at UCLA, DBS was initially widely used for treating refractory pain. Then it was used to abate pain of central origin, such as poststroke pain and other causes of damage to the central nervous system.

“A group of scientists in Grenoble, France, first used it implanted chronically for treatment of essential tremor,” De Salles says. “This application provided a remarkable improvement of tremor when the electrode was implanted in the ventro-nucleous intermedius of the thalamus.”

Because of the remarkable results observed, experts tried DBS for treating PD where tremor is prevalent. “It was developed further for other symptoms of Parkinson’s disease, such as rigidity and bradykinesia, by implanting the electrode in other areas of the brain, such as the globus pallidus internum [GPI] and subthalamic nucleus [STN],” De Salles says.

As Paul Larson, MD, an associate clinical professor of neurological surgery in the University of California, San Francisco department of neurological surgery and chief of neurosurgery service at the San Francisco VA Medical Center, explains, more than 70,000 patients worldwide have been implanted with DBS, which is indicated when patients have advanced in their disease to the point where at least one of two things has happened: The patient has developed motor fluctuations for which medications are no longer effective throughout the day and/or the patient has developed bothersome dyskinesias.

“The concept of DBS is that when current flows through the electrode, it can reversibly alter the abnormal function of the brain structure that is being targeted,” says Devin Binder, MD, PhD, a neurosurgeon and spine surgeon at the Southern California Center for Neuroscience and Spine at Chapman Medical Center. “In the case of Parkinson’s, placing the electrode in the subthalamic nucleus alters the structure and markedly alters the symptoms of Parkinson’s disease.”

According to Michael Okum, MD, national medical director for the National Parkinson Foundation and codirector of the Movement Disorders Center located within the McKnight Brain Institute and the University of Florida College of Medicine, many human central nervous system diseases are associated with abnormal patterns of physiologic activity in brain circuitry.

“Based on a plethora of animal and human research, we have learned that rates and patterns of electrophysiological activity are abnormal in many of these basal ganglia circuits,” Okum says. “We can change the rates and patterns of activity by implanting brain stimulators into one of many targets, including the thalamus, subthalamic nucleus, globus pallidus, internal capsule, nucleus accumbens, and other regions.”

As Okum explains, DBS devices can be appropriately placed in an operating room setting utilizing advanced brain imaging, stereotactic targeting, microelectrode recording, and macrostimulation. “The placement will often need to be within a millimeter or less of the optimal target to improve symptoms and avoid side effects,” Okum says. Following placement, the electrodes remain implanted and adjustments can be made to DBS settings (eg, pulse width, frequency, amplitude) for changes in symptoms over time.

“There are actually four electrodes on the tip of the DBS lead. So during the programming session in the neurologist’s office, all of the combinations are tried out and whatever stimulation parameters that the patient has good effects on are what are eventually used,” Binder says. “It also may allow the medication to be lessened or even eliminated.”

At its core, DBS is based on cardiac pacemaker technology with a combination battery and pulse generator unit placed under the skin in the chest and one or two stimulating wires that are placed into a part of the brain that coordinates body movements.

The electrode is placed very precisely into a specific target area depending on the underlying condition. “For Parkinson’s disease, the target is either the subthalamic nucleus or the globus pallidus interna,” says Richard Bucholz, MD, a professor of neurosurgery at St. Louis University School of Medicine. “By stimulating these deep-seated nuclei, the neurotransmitters in the area are essentially exhausted, which ameliorates the symptoms associated with PD, as the output of these areas, usually balanced by the output of the substantia nigra [SN], is excessive due to loss of cells in the SN. In effect, stimulation of these areas restores the balance between the STN, GPI, and SN usually seen in normal humans and reduces the symptoms associated with late stage PD.”

These targets were previously sites where neurosurgeons performed minute lesions to improve movement disorder symptoms, De Salles says. Therefore, the most accepted theory of the mechanism of action of DBS is that the high-frequency electrical stimulation delivered by the device leads to inactivity of the tissue surrounding the implanted electrode, mimicking a lesion. This theory is debated and there is some evidence that depending on the target, other pathways beyond the site of stimulation are affected to improve symptoms.

Initially the FDA approved DBS for chronic pain procedures. However, over the years this application became less prevalent, and the modern devices were not approved for this application. Now the FDA has approved DBS for essential tremor and PD as well as for other applications, including dystonia and obsessive-compulsive disorders. Other applications, such as for epilepsy and depression, are close to approval while more exotic applications, such as for morbid obesity, Alzheimer’s disease, and tinnitus, are under investigation.

As a result of its increased use, DBS is now implemented in almost all major medical centers where a department of neurosurgery exists. “Surgeons have to be specifically trained for the procedure,” De Salles says. “The field is growing because the number of indications for DBS is increasing rapidly. It also has the advantage of being an adjustable procedure and reversible. Therefore, it attracts the attention of neurologists and patients alike. More and more young neurosurgeons are interested in learning the technique.”

Identifying Candidates
Movement disorder patients, including those suffering from essential tremor, PD, and dystonia, are the major candidates for the DBS procedure. “Several dedicated academic centers also implant DBS for chronic pain,” De Salles says. “Patients are usually chosen from a pool of patients who have failed medical therapy. Although due to the effectiveness of DBS and the acceptance among patients and physicians, the procedure is being proposed for early-stage disease. This is mostly accepted for Parkinson’s disease.”

Essential tremor patients become candidates when their quality of life is hampered by the intensity of their tremors to the point that they cannot care for themselves and subsequently experience social impairment. The same is true for dystonia and obsessive-compulsive disorder patients. Patients must be fit for surgery as far as cardiac reserve and mental status and be capable of collaborating with physicians to monitor their therapy.

“The best candidates are those who still have a good response, at least some of the time, to medications,” Larson says. “The symptoms that are helped most with DBS are tremor; stiffness; slowness of movement, including freezing when the medications have worn off; walking difficulties; and dyskinesias. The best candidates are those who are bothered most by those particular symptoms. Patients who have ‘atypical’ Parkinson’s disease, significant memory or other cognitive difficulties, and other medical conditions that can increase the risk of surgery are not good candidates.”

Binder says physicians need to ensure that a patient has been correctly diagnosed with PD. “That sounds obvious, but in some cases they may have a slightly different movement disorder that is not a good candidate for DBS,” Binder says. “The patient needs a good neurologist who has diagnosed their Parkinson’s. They also need to have had an initial good response to the Parkinson’s medication but now the medication has started to lose effectiveness. They may wear off or the patients may have side effects from the medications. And lastly, you need to make sure they don’t have cognitive decline because DBS requires a commitment on the part of the physicians as well as the patient.”

Risks Involved
The procedure is quite demanding, as the targets are small and deeply situated within the brain. “Therefore, significant technology is required to place the lead with the best efficacy: microelectrode recording during the procedure to make certain the neurons around the electrode are from the appropriate population of cells; an awake procedure to allow trial stimulation of the leads; intraoperative navigational computers; and intraoperative imaging consisting either of CT or MRI scanning,” Bucholz says. “Given these requirements, relatively few medical centers are performing DBS, and those centers are usually tertiary academic centers, given the need for intraoperative neurophysiologists and imaging specialists.”

De Salles stresses that the risks of DBS include intracranial bleeding, paralysis, and death. “These are the risks of any major surgery in the brain; however, DBS is considered a minor surgery in the realm of neurosurgery,” De Salles says. The risks of devastating complications runs less than 0.5%, while minor complications such as infection and hardware breakage have been reported in between 1% and 13% of cases. The benefits include the reversibility of the procedure and the major improvement of symptoms when properly indicated. Other risks include failing to place the electrode in the best possible location, the breaking or malfunctioning of the system, and symptoms failing to improve as much as expected.

Recovery from surgery is fast, requiring only a few days. “[Typically] one day admitted to the hospital is expected; discharge is followed by one week of complete recovery; and a second surgery within two to three weeks for implant of the pulse generator in the chest wall with connection to the intracranial electrodes,” De Salles says. “This generator will deliver the electricity to the brain. Following the generator implant, the patient undergoes several programming sessions where the physician adjusts the device to the patient symptoms and medication intake.” Patients should be followed at six-month intervals and usually will need a generator (battery) change approximately every four years.

Key Indications
Physicians referring a patient for DBS should be aware of the need to program the device and, as with any electronic device, the patient can expect the need for proper maintenance.

“The patients will become dependent on this electronic device to function, as if they were electronic themselves,” De Salles says. “Failure of the device, infection, breakage of wires, movement of electrodes, intolerance to the presence of the device, and side effects of stimulation all can disturb results and patients’ quality of life, sometimes leading patients to end up in an emergency room paralyzed.”

De Salles says physicians should advise patients of the possibility of the complications previously mentioned. Patients should also be made aware that regarding medications, the DBS therapy will need to be followed and adjusted when necessary. “The disease’s progress and the stimulation should be adjusted accordingly,” De Salles says. “DBS is not a cure for any disease; it is just a measure to improve the patients’ tolerance to the diseases’ symptoms, controlling and managing the symptoms, many times also needing medication to add to the effects of the DBS.” Physical therapy may be necessary for patients who have been inactive for many years before undergoing DBS surgery, as DBS surgery is capable of restoring patients to normal activities.

Larson points out that patients tend to focus on the surgery as the “big event,” but the real work comes after DBS surgery. “The device must be ‘programmed’ to result in the most improvement of symptoms with the least side effects,” Larson says. “Also, the Parkinson’s medications must be adjusted and frequently reduced to work well in concert with the stimulation.”

Physicians need to be aware that DBS is not a cure for PD and, as discussed here, not everyone is a good candidate for DBS. “They should also be aware that the process of programming the device after surgery requires regular visits to the neurologist in the first six months, sometimes as frequently as every four to six weeks,” Larson says. “It’s important to tell patients that DBS can reduce some of the symptoms of Parkinson’s disease quite significantly but does not cure the disease. It cannot help all of the symptoms and does have small but real risks. However, in patients who are candidates, DBS can significantly improve quality of life and reduce the disability caused by Parkinson’s.”

Bucholz adds that the procedure is highly efficacious, with multiple articles indicating this as well as the procedure’s cost-effectiveness, and it is applicable to almost any patient with PD who is not demented. “Physicians should encourage their patients to consider the procedure even though many are fearful of the procedure,” Bucholz says. “We have patients who have gone through it and are delighted they did.”

— Maura Keller is a Minneapolis-based writer and editor.

Deep Brain Stimulation Transforms Lives of PD Patients
Patients see dramatic, life-transforming changes after the deep brain stimulation (DBS). Some patients liken the transformation to a switch that turns off the tremors. DBS can be a game-changer for Parkinson’s disease (PD) patients.

Up to 5% of the general population is affected by essential tremors and about one in 1,000 have PD, a number that increases to one in 100 for those over the age of 60. Movement disorders such as PD and essential tremors are more common than many people think, says Kelvin Chou, MD, codirector of the Surgical Therapies Improving Movement (STIM) program and an associate professor in the University of Michigan’s neurology department.

“Movement disorders can certainly affect someone’s quality of life, especially those with tremors. In someone living with essential tremor, the tremors are most prominent when the person is using their hands. Eating, writing—those types of activities will be affected,” says Chou. “Things we take for granted like signing a check, shaving, or applying makeup can be very, very difficult for people with essential tremor to do.”

Tremors from PD do not usually affect patients’ activities except in severe cases. However, many people are embarrassed by uncontrollable movement and don’t go out to restaurants or socialize.

Medications can be effective for about 70% of patients with essential tremor and can work well for those with PD. But for many PD patients, the symptoms begin to worsen or don’t respond as well to medication over time.

“When that starts to happen, when a Parkinson’s patient is forced to take medications every couple of hours just to keep themselves going or if medications don’t help an essential tremor, that’s when deep brain stimulation may be an option,” Chou says.

“Not only do we have the anecdotal evidence of patients telling us that their lives have been changed, there have been careful studies comparing deep brain stimulation to using medication alone,” says Parag Patil, MD, PhD, codirector of the STIM program and an assistant professor of neurosurgery.

“These studies, particularly in Parkinson’s disease, have shown that the quality of life improvements of carefully chosen patients treated with deep brain stimulation are much better than patients treated with medication alone,” says Patil. “Deep brain stimulation is like a pacemaker. The wire goes in and it creates an electrical signal that acts kind of like a metronome to keep the brain in order.”

Patil says there’s a team of experts at the University of Michigan who spend a lot of time assessing whether a patient is a good candidate for deep brain stimulation. That multidisciplinary team includes a neurosurgeon, neurologist, speech pathologist, and social worker. In addition, there is a neuropsychologist, who specializes in understanding thinking patterns associated with neurologic diseases. Patients also have access to physical therapists and psychiatrists.

“It’s a real advantage to have this significant breadth of expertise. We can look beyond just the neurologic side and include the psychiatric issues and the patients’ home life through social work. It provides a very rich therapy,” Patil says.

When the university started its program five years ago, about four or five patients were treated with deep brain stimulation each year. That’s now up to about 30 patients each year, and Patil says there are many people in Michigan and all over the world who could benefit from the surgery.

“Our goal is to increase awareness through educational programs and outreach to community physicians so that appropriate patients can get this really beneficial therapy,” Patil says.

— Source: University of Michigan Health System