DEEP BRAIN STIMULATION

Electrical stimulation of the brain is an important therapy for refractory neurological disorders such as drug resistant Parkinson's disease and severe tremor and has become an area of active clinical research in both neurology and psychiatry. Using a technique called deep brain stimulation (DBS), small electrical leads are placed into the brain using stereotactic localization. A special head frame is attached to the skull under local anesthesia, and electrodes are implanted using internal brain targets located with reference to anatomical landmarks determined by brain imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI). This technique allows for the precise targeting of specific brain sites or nuclei. Insertion of electrodes can be done without damage to adjacent tissue. These electrodes are connected by a wire to a pacemaker implanted in the chest that generates electrical stimulation. Stimulation parameters can be modified by manipulation of the pacemaker.

Unlike ablative surgery that results in irreversible damage of brain tissue from the intentional destruction of targeted areas, the effects of DBS are reversible. The stimulator can be turned off, and the electrodes can generally be removed without any significant aftereffects. DBS differs from other methods that employ electrical stimulation of the central nervous system. Electroconvulsive therapy (ECT), primarily used to treat severe depression, stimulates the brain using electrodes placed on the scalp. Transcranial magnetic stimulation induces electrical currents in the brain using external magnetic coils. Electrical stimulation in the neck of the vagus nerve has been demonstrated to reduce epileptic seizures. Cortical stimulation of the brain is also employed as a treatment for chronic pain disorders (Greenberg).

Electrical stimulation of the brain is also used as a diagnostic tool in the treatment of epilepsy and as a means to localize specific brain areas in order to avoid injury during surgical procedures. Electrical stimulation has also been applied within the peripheral nervous system for neuroprosthethic applications such as reconstituting motor function in a paralyzed limb.

Historical Considerations

The modern history of electrical stimulation of the brain dates to the nineteenth century During this period the French surgeon and anthropologist Paul Broca (1824–1880) correlated speech with an area in the left hemisphere that is known as Broca's area, and the English neurologist John Hughlings Jackson hypothesized that electrical activity in the cortex could result in seizures. In tandem with these efforts to correlate cerebral structure and function, early neurophysiologists engaged in animal experimentation using electrical stimulation In 1870 the German neurologists Eduard Hitzig and Gustav Fritsch demonstrated motor activity in a dog following stimulation (Thomas and Young). In 1873 the Scottish neurologist David Ferrier induced contralateral seizures in a dog after unilateral hemispheric stimulation.

The first known electrical stimulation of the human brain was conducted by the American neurosurgeon Roberts Bartholow in Cincinnati, Ohio, in 1874 on a terminally ill woman with locally invasive basal cell carcinoma that had eroded her skull and left her brain exposed. Bartholow demonstrated that the dura mater covering the brain was insensate, that motor activity on one side of the body could be induced by stimulation of the opposite hemisphere, and that electrical stimulation of the brain could induce localized seizures and transient loss of consciousness when the amount of current was increased. The patient subsequently died from recurrent seizure activity. Contemporaries harshly criticized Bartholow on ethical grounds because of the fatal complications of the intervention, the uncertain nature of the patient's "consent," and the suffering that she experienced (Morgan).

Early electrical stimulation of the brain was used as a method of mapping cerebral cortical function, matching the site of stimulation of the brain's surface with the patient's response during operations under local anesthesia. Pioneering work was done by two American neurosurgeons: Harvey Cushing in the early twentieth century and Wilder Penfield, who later in the century used electrical stimulation in his study of epilepsy and the mapping of cognitive function. An important advance was the development in 1947 of stereotactic surgery, which enabled brain targets to be precisely located in three dimensions. With this technique, electrodes could now be inserted in the brain without the completion of a full craniotomy in which the entire skull needs to be opened (Gildenberg, 1990).

Robert G. Heath first described electrical stimulation for the control of chronic pain in his 1954 book, Studies in Schizophrenia. In the 1960s and 70s investigators demonstrated that deep stimulation of selected targets within the brain was demonstrated to relieve pain In 1985, the Swiss neurosurgeon, Jean Siegfried noted that stimulation of the thalamus for pain control could improve tremor in a patient with Parkinson's disease (Gildenberg, 1998).

The Psychosurgery Debate

Research involving electrical stimulation of the brain was closely linked to the broader debate over psychosurgery in the 1960s and 1970s (Fins, 2003). Commentators from that era worried about the use of electrical stimulation of the brain as a means of behavior control to address social problems such as crime and civic unrest. These concerns were prompted, in part, by the work of José M. R. Delgado who advanced the idea of "psychocivilizing society" using a brain implant that could be operated by remote control. Delgado came to international attention in 1965 when he stopped a charging bull in a bullring using a "stimoceiver" he had developed. Speculation was enhanced by popular novels such as Michael Crichton's The Terminal Man whose main character underwent electrical stimulation of the brain to treat violent behavior.

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, authorized by the National Research Act of 1974, was specifically ordered by the U.S. Congress to issue a report on psychosurgery (National Research Act of 1974. U.S. Statutes at Large). The National Commission, which issued its report in 1977, included electrical stimulation of the brain under its definition of psychosurgery, noting that "psychosurgery includes the implantation of electrodes, destruction or direct stimulation of the brain by any means" when its primary purpose was to "control, change, or affect any behavioral or emotional disturbance" (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research). The National Commission's definition of psychosurgery excluded brain surgery for the treatment of somatic disorders such as Parkinson's disease or epilepsy or for pain management.

Of the National Commission, the Behavioral Control Research Group of the Hastings Institute (Blatte), and the American Psychiatric Association's Task Force on Psychosurgery (Donnelly), none found reliable evidence that psychosurgery had been used for social control, for political purposes, or as an instrument for racist repression as had been alleged. Contrary to expectations of the day, the National Commission did not recommend that psychosurgical procedures be banned. Instead, it found sufficient evidence of efficacy of some psychosurgical procedures to endorse continued experimentation as long as strict regulatory guidelines and limitations were in place.

Although allegations of mind control were never substantiated, contemporary media reports about modern deep brain stimulation often allude to these earlier fears This misuse of historical analogy has the potential to distort current policy regarding the regulation of this novel technology (Fins, 2002).

Clinical Applications in Neuromodulation

The modern era of neuromodulation began in 1987 when the French neurosurgeon Alim Benabid noted improvements of parkinsonian tremor following stimulation of the thalamus (Speelman and Bosch). While engaged in mapping with electrodes prior to ablative surgery for Parkinson's disease, Benabid discovered that electrical stimulation of specific targets could modulate motor symptoms and tremor—a technique that came to be known as neuromodulation. These observations inspired him to develop the modern deep brain stimulator in use today (Fins and Schachter).

Deep brain stimulation is viewed as the standard of care for the treatment of refractory Parkinson's disease and is no longer investigational. In 1997 the U.S. Food and Drug Administration (FDA) approved use of the deep brain stimulator for refractory Parkinson's disease and essential tremor (Blank). DBS has been found effective in prospective, double-blind studies in patients with advanced Parkinson's disease (Deep-Brain Stimulation, 2001; Kumar et al.).

Complications can be related to the procedure, device, or stimulation, and they include hemorrhage, infection, seizures, and hardware-related complications. Such complications can necessitate revision or removal of the device at a rate per electrode year of 8.4 percent (Oh et al.). In one large series of patients, there were no fatalities or permanent severe neurological complications, although 6 percent of patients had some persistent neurological complication (Beric et al.).

In addition to being used to treat Parkinson's disease, neuromodulation using DBS has been used to treat chronic pain and manage epilepsy (Kopell and Rezai). Cortical mapping continues, with more electronic sophistication. Such mapping is being used to guide neurosurgical procedures; to prevent injuries to critical areas, such as those associated with speech or movement, during operations on the brain; and to precisely locate areas of the brain involved with epilepsy, occasionally by provoking seizures through stimulation (Feindel).

Investigational Applications

Research in deep brain stimulation is blurring the disciplinary boundaries between neurology and psychiatry. French investigators have discovered that DBS caused transient acute depression in a patient with Parkinson's disease whose motor function had improved markedly through DBS intervention (Bejjani et al.). Investigators are conducting clinical trials for the use of DBS for severe psychiatric illnesses such as obsessive–compulsive disorder using techniques pioneered in the treatment of movement disorders (Roth et al.; Rapoport and Inoff-Germain). Nicholas D. Schiff and colleagues have proposed the use of DBS for the modulation of consciousness after severe traumatic brain injury (Schiff, Plum, and Rezai).

Ethical Considerations

Deep brain stimulation raises special concerns because neuromodulation techniques deal with the direct stimulation of the brain. No other organ is so closely involved with concepts of mind or self, self-determination and consent.

POTENTIAL ALTERATION OF THE SELF. Interventions involving brain structure or function may result in alterations in cognition, memory, or emotions that may have a bearing on personhood. The potential of DBS to alter brain function may lead some to argue categorically against these interventions. This position would fail to appreciate that psychoactive drugs and cognitive rehabilitation alter brain states and that DBS can be used to restore brain functions that had themselves been altered by injury or disease.

The use of DBS as a potential agent of cognitive rehabilitation raises the question of whether helping a patient regain self-awareness is always an ethical good (Fins, 2000). Partial recovery of cognitive function could theoretically lead to greater awareness of impairment and increased suffering. These perceptions, which may also accompany improvement from more conventional rehabilitation, might be reversed with cessation of stimulation or be treated with antidepressant therapy.

THERAPEUTIC VERSUS INVESTIGATIONAL USE. Given the rapid development of this field, it is important to determine whether the application of deep brain stimulation to a particular disease is therapeutic or investigational. Historically, a treatment has moved from investigational use to therapeutic use when it is shown to relieve the symptoms it is intended to relieve with an acceptable degree of risk and when a significant proportion of physicians, especially those working in the field, are convinced that the intended outcome will appear without adverse long- or short-term effects that outweigh the benefits. This delineation between research and therapy has implications for the informed-consent process and the ability of surrogates to provide consent for DBS when a patient or subject lacks decisionmaking capacity. In the early twenty-first century DBS is recognized as therapeutic for the management of chronic pain, Parkinson's disease, and other movement disorders. It remains investigational for other indications.

Today, the use of a device such as the deep brain stimulator goes through several investigational stages before it is accepted as therapeutic. Formal mechanisms are in place to codify this transition. The FDA uses the investigational device exemption process to regulate devices that pose significant risk, such as the deep brain stimulator (Pritchard, Abel, and Karanian). FDA procedures, which supplement institutional review board (IRB) oversight of clinical trials, are designed to establish the safety and efficacy of devices and are required by law.

Once a device has been approved for use in humans, a clinical trial can proceed to assess the safety and efficacy of the device for a particular indication. Use of a device is deemed therapeutic when its safety and efficacy have been demonstrated in prospective trials, the most rigorous being ones that are double-blinded and randomized (a double-blinded study is one in which during the course of the study neither the subjects nor the conductors of the study know which subjects are in the active therapy or placebo group). Blinded studies can be conducted in the evaluation of DBS. Once the electrodes have been implanted, patients can be blinded to whether they are receiving stimulation, and their responses can be evaluated. Such methodological rigor is essential in the assessment of DBS because of the potential for a powerful placebo effect. The placebo effect has been shown to improve motor performance of patients with Parkinson's disease who were led to believe that they were being stimulated (Pollo et al.).

Demarcating the therapeutic use of DBS from the investigational may be difficult. For example, the use of an approved device does not, in itself, mean that an intervention is therapeutic. In these cases, the intent of the physician or clinical investigator may be important. Many would assert that if the physician's intent is to produce effects generally beneficial to the patient that have previously been demonstrated in similar cases, the intervention can be considered therapeutic. But when the investigator intends to use an approved device to increase knowledge of safety or efficacy for an approved indication or use the device at a new anatomical site or for a new indication, such interventions should be considered to be investigational and undergo review by an IRB.

Because investigational uses of DBS require more regulatory oversight, clinicians might be biased to classify borderline uses of DBS as therapeutic When it is unclear whether the use of DBS is therapeutic or investigational, clinicians should seek the guidance of their local IRB to mitigate this potential conflict of interest.

INFORMED CONSENT. The delineation of DBS as either therapeutic or investigational is also critical given ethical norms that govern informed consent. Given the ongoing investigational nature of many DBS procedures, potential candidates for stimulation need to be informed of whether the proposed procedure is therapeutic or experimental. Physicians who obtain consent from patients for therapeutic procedures should explain the risks, benefits, and alternatives so that the patient, or a surrogate authorized to consent for medical treatment, can provide consent.

Clinicians should seek to maintain the patient's voluntariness and ability to make an informed and reasonable decision about treatment with DBS. Those obtaining consent should appreciate that the chronic nature of the illness and desperation may lead a patient to consent to any treatment that promises symptomatic relief.

When individuals are approached for enrollment in an IRB-approved clinical trial, it is especially important to state the investigational nature of the intervention. Investigators should be careful to avoid the suggestion of a "therapeutic misconception" that falsely equates a clinical trial with safe and effective therapy (Applebaum et al.).

DBS RESEARCH IN THE DECISIONALLY INCAPACITATED. Individuals with severe psychiatric illness or head trauma, who may become candidates for enrollment in DBS clinical trials, may lack decision-making capacity. When these individuals are unable to engage in the informed-consent process, they are considered a vulnerable population and in need of special protections. While surrogates are generally allowed to consent to therapeutic procedures, their authority is more constrained when permission is sought for enrollment in a clinical trial unless they have been authorized through an advance directive for prospective research.

The National Bioethics Advisory Commission (NBAC), in its 1998 report, Research Involving Persons with MentalDisorders That May Affect Decisionmaking Capacity, proposed guidelines to regulate the conduct of research on individuals who are unable to provide consent. While the NBAC recommendations were never enacted into law, they do point to the ethical complexity of neuromodulation research in several cases: when subjects lack decision-making capacity, when the research has yet to demonstrate the prospect of direct medical benefit, and when the research poses more than minimal risk.

BALANCING THE PROTECTION OF HUMAN SUBJECTS WITH ACCESS TO RESEARCH. When considering the balance between the protection of human subjects and access to neuromodulation research, it is important to ask whether current ethical norms deprive decisionally incapacitated individuals of interventions that have the potential to promote self-determination by restoring cognitive function (Fins, 2000). While the ethical principles of respect for persons, beneficence, and justice require that decisionally incapacitated subjects are protected from harm, these principles can also be invoked to affirm a fiduciary obligation to promote well-designed and potentially valuable research for this historically underserved population (Fins and Miller; Fins and Schiff). This justice claim becomes especially compelling as developments in neuromodulation demonstrate growing clinical potential (Fins, 2003).

joseph j. fins

SEE ALSO: Behaviorism; Behavior Modification Therapies; Electroconvulsive Therapy; Emotions; Freedom and Free Will; Informed Consent: Issues of Consent in Mental Healthcare; Neuroethics; Psychosurgery, Ethical Aspects of; Psychosurgery, Medical and Historical Aspects of; Research Policy: Risk and Vulnerable Groups; Technology

BIBLIOGRAPHY

Applebaum, Paul S.; Roth, Loren H.; Lidz, Charles W.; et al. 1987. "False Hopes and Best Data: Consent to Research and the Therapeutic Misconception." Hastings Center Report 17(2): 20–24.

Bejjani, B.-P.; Damier, P.; Arnulf, I.; et al. 1999. "Transient Acute Depression Induced by High-Frequency Deep-Brain Stimulation." New England Journal of Medicine 340(19): 1476–1480.

Beric, A.; Kelly, P. J.; Rezai, A.; et al. 2001. "Complications of Deep Brain Stimulation." Stereotactic Functional Neurosurgery 77(1–4): 73–78.

Blank, Robert H. 1999. Brain Policy: How the New Neuroscience Will Change Our Lives and Our Politics. Washington, D.C.: Georgetown University Press.

Blatte, H. 1974. "State Prisons and the Use of Behavior Control." Hastings Center Report 4(4): 11.

Cushing, Harvey. 1909. "A Note upon the Faradic Stimulation of the Postcentral Gyrus in Conscious Patients." Brain 32: 44–53.

Deep-Brain Stimulation for Parkinson's Disease Study Group. 2001. "Deep-Brain Stimulation of the Subthalamic Nucleus or the Pars Interna of the Globus Pallidus in Parkinson's Disease." New England Journal of Medicine 345(13): 956–963.

Delgado, José M. R. 1969. Physical Control of the Mind: Toward a Psychocivilized Society, ed. Ruth N. Anshen. New York: Harper and Row.

Donnelly, J. 1978. "The Incidence of Psychosurgery in the United States, 1971–1973." American Journal of Psychiatry 135(12): 1476–1480.

Feindel, William. 1982. "The Contributions of Wilder Penfield to the Functional Anatomy of the Human Brain." Human Neurobiology 1(4): 231–234.

Fins, Joseph J. 2000. "A Proposed Ethical Framework for Interventional Cognitive Neuroscience: A Consideration of Deep Brain Stimulation in Impaired Consciousness." Neurological Research 22(3): 273–278.

Fins, Joseph J. 2002. "The Ethical Limits of Neuroscience." Lancet Neurology 1(4): 213.

Fins, Joseph J. 2003. "From Psychosurgery to Neuromodulation and Palliation: History's Lessons for the Ethical Conduct and Regulation of Neuropsychiatric Research." Neurosurgery Clinics of North America 14(2): 303–319.

Fins, Joseph J., and Miller, Franklin G. 2000. "Enrolling Decisionally Incapacitated Subjects in Neuropsychiatric Research." CNS Spectrums 5(10): 32–42.

Fins, Joseph J., and Schiff, Nicholas D. 2000. "Diagnosis and Treatment of Traumatic Brain Injury." Journal of the American Medical Association 283(18): 2392.

Gaylin, Willard M.; Meister, Joel S.; and Neville, Robert C., eds. 1975. Operating on the Mind: The Psychosurgery Conflict. New York: Basic.

Gildenberg, Philip L. 1990. "The History of Stereotactic Surgery." Neurosurgery Clinics of North America 1(4): 765–780.

Gildenberg, Philip L. 1998. "The History of Surgery for Movement Disorders." Neurosurgery Clinics of North America 9(2): 283–293.

Greenberg, Benjamin D. 2002. "Update on Deep Brain Stimulation." Journal of ECT 18(4): 193–196.

Kopell, Brian Harris, and Rezai, Ali R. 2000. "The Continuing Evolution of Psychiatric Neurosurgery." CNS Spectrums 5(10): 20–31.

Kumar, R.; Lozano, A. M.; Kim, Y. J.; et al. 1998. "Double-Blind Evaluation of Subthalamic Nucleus Deep Brain Stimulation in Advanced Parkinson's Disease." Neurology 51(3): 850–855.

Morgan, James P. 1982. "The First Reported Case of Electrical Stimulation of the Human Brain." Journal of the History of Medicine 37(1): 51–64.

National Bioethics Advisory Commission. 1998. Research Involving Persons with Mental Disorders That May Affect Decisionmaking Capacity. Rockville, MD: National Bioethics Advisory Commission.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 1977. "Use of Psychosurgery in Practice and Research: Report and Recommendations of National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research." Federal Register 42(99): 26318–26332.

National Research Act of 1974. U.S. Statutes at Large 88: 342.

Oh, Michael Y.; Abosch, Aviva; Kim, Seong H.; et al. 2002. "Long-Term Hardware Related Complications of Deep Brain Stimulation." Neurosurgery 50(6): 1268–1274.

Penfield, Wilder. 1977. No Man Alone: A Neurosurgeon's Life. Boston: Little, Brown.

Pollo, Antonella; Torre, Elena; Lopiano, Leonardo; et al. 2002. "Expectation Modulates the Response to Subthalamic Nucleus Stimulation in Parkinsonian Patients." NeuroReport 13(11): 1383–1386.

Pritchard, W. F.; Abel, D. B.; and Karanian, J. W. 1999. "The U.S. Food and Drug Administration Investigational Device Exemptions and Clinical Investigation of Cardiovascular Devices: Information for the Investigator." Journal of Vascular and Interventional Radiology 10(2): 115–122.

Rapoport, J. L., and Inoff-Germain, G. 1997. "Medical and Surgical Treatment of Obsessive–Compulsive Disorder." Neurologic Clinics 15(2): 421–428.

Roth, Robert M.; Flashman, Laura A.; Saykin, Andrew J.; and Roberts, David W. 2001. "Deep Brain Stimulation in Neuropsychiatric Disorders." Current Psychiatric Reports 3: 366–372.

Schiff, Nicholas D.; Plum, F.; and Rezai, A. R. 2002. "Developing Prosthetics to Treat Cognitive Disabilities Resulting from Acquired Brain Injuries." Neurological Research 24(2): 116–124.

Speelman, J. D., and Bosch, D. A. 1998. "Resurgence of Functional Neurosurgery for Parkinson's Disease: A Historical Perspective." Movement Disorders 13(3): 582–588.

Thomas, R. K., and Young, C. D. 1993. "A Note on the Early History of Electrical Stimulation of the Human Brain." Journal of General Psychology 120(1): 73–81.

Deep Brain Stimulation

Definition
Purpose
Demographics
Description
Diagnosis/Preparation
Aftercare
Risks
Normal results
Morbidity and mortality rates
Alternatives

Definition

Deep brain stimulation (DBS) delivers a constant low electrical stimulation to a small region of the brain, through implanted electrodes connected to an implanted battery. It is used to partially restore

normal movements in Parkinson’s disease, essential tremor, and dystonia.

Purpose

Parkinson’s disease is due to degeneration of a group of cells called the substantia nigra. These cells interact with other brain regions to help control movement. The normal signals from the substantia nigra inhibit these other regions, and so when it degenerates, these regions become overactive. The electrical signals from the DBS electrodes mimic the inhibitory function of the substantia nigra, helping to restore more normal movements.

The substantia nigra normally releases the chemical dopamine, which exerts its inhibitory action on the globus pallidus interna (GPi) and the subthalamic nucleus (STN). For Parkinson’s disease, deep brain stimulation is performed on these two centers. The target for DBS in dystonia is the GPi as well. Treatment of essential tremor usually targets the thalamus.

Each of these brain regions has two halves, which control movement on the opposite side of the body: right controls left, and left controls right. Unilateral DBS may be used if the symptoms are much more severe on one side. Bilateral DBS is used to treat symptoms on both sides.

Demographics

Parkinson’s disease affects approximately one million Americans. The peak incidence is approximately age 62, but young-onset PD can occur as early as age 40. Because young-onset patients live with their disease for so many more years, they are more likely to become candidates for surgery than older-onset patients. In addition, younger patients tend to do better and suffer fewer adverse effects of surgery. Approximately 5% of older PD patients receive one form or another of PD

surgery. Many more develop the symptoms for which surgery may be effective, but either develop them at an advanced age, making surgery inadvisable, or decide the risks of surgery are not worth the potential benefit, or do not choose surgery for some other reason.

Essential tremor is more common than Parkinson’s disease, but rarely becomes severe enough to require surgery. Dystonia is a very rare condition, and the number of patients who have received DBS as of 2003 is under 100.

Description

Deep brain stimulation relies on implanting a long thin electrode deep into the brain, through a hole in the top of the skull. In order to precisely locate the target area and to ensure the probe is precisely placed in the target, a “stereotactic frame” is used. This device is a rigid frame attached to the patient’s head, providing an immobile three-dimensional coordinate system, which can be used to precisely track the location of the GPi or STN and the movement of the electrode.

For unilateral DBS, a single “burr hole” is made in the top of the skull. Bilateral DBS requires two holes. A strong topical anesthetic is used to numb the skin while this hole is drilled. Since there are no pain receptors in the brain, there is no need for deeper anesthetic. In addition, the patient must remain awake in order to report any sensory changes during the surgery. The electrode is placed very close to several important brain structures. Sensory changes during electrode placement may indicate the electrode is too close to one or more of these regions.

Once the burr hole is made, the surgeon inserts the electrode. Small electric currents from the electrode are used to more precisely locate the target. This is harmless, but may cause twitching, light flashes, or other sensations. A contrast dye may also be injected into the spinal fluid, which allows the surgeon to visualize the brain’s structure using one or more imaging techniques. The patient will be asked to make various movements to assist in determining the location of the electrode.

The electrode is connected by a wire to an implanted pulse generator. This wire is placed under the scalp and skin. A small incision is made in the area of the collarbone, and the pulse generator is placed there. This portion of the procedure is performed under general anesthesia.

Diagnosis/Preparation

DBS for Parkinson’s disease is considered as an option in a patient who is still responsive to levodopa (used to treat symptoms) but has developed motor complications. These include the rapid loss of benefit from a single dose (wearing off), unpredictable fluctuations in benefit (on-off), and uncontrolled abnormal movements (dyskinesias). Essential tremor patients who are candidates for surgery are those whose tremor is unsatisfactorily controlled by medications and whose tremor significantly impairs activities of daily living. Similar criteria apply for dystonia patients.

The patient who is a candidate for DBS discusses all the surgical options with his neurologist before deciding on deep brain stimulation. A full understanding of the risks and potential benefits must be understood before consenting to the surgery.

The patient will undergo a variety of medical tests, and one or more types of neuroimaging procedures, including MRI, CT scanning, angiography (imaging the brain’s blood vessels) and ventriculography (imaging the brain’s ventricles). On the day of the surgery, the stereotactic frame is fixed to the patient’s head. A local anesthetic is used at the four sites where the frame’s pins contact the head; there may nonetheless be some initial discomfort. A final MRI is done with the frame in place, to set the coordinates of the targeted area of the brain in relation to the frame.

The patient will receive a mild sedative to ease the anxiety of the procedure. Once the electrodes are positioned, the patient receives general anesthetic to implant the pulse generator.

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

Deep brain stimulation is performed by a neurosurgeon in a hospital.

Aftercare

The procedure is lengthy, and the patient will require a short hospital stay afterward to recover from the surgery. Following the procedure itself, the patient meets several times with the neurologist to adjust the stimulation. The pulse generator is programmable, and can be fine-tuned to the patient’s particular needs. This can provide a higher degree of symptom relief than lesioning surgeries, but requires repeated visits to the neurologist. Pulse generator batteries must be replaced every three to five years. This is done with a small incision as an outpatient procedure. Since the generator is in the chest area, no additional brain surgery is required.

The patient’s medications are adjusted after surgery, with a reduction in levodopa likely in most patients who receive DBS of the subthalamic nucleus.

Risks

Deep brain stimulation entails several risks. There are acute surgical risks, including hemorrhage and infection, and the risks of general anesthesia. The electrodes can be placed too close to other brain regions, which can lead to visual defects, speech problems, and other complications. These may be partially avoided by adjusting the stimulation settings after the procedure. Because a device is left implanted under the skin, there is the risk of breakage or malfunction, which requires surgical removal.

A patient with implanted electrodes must not receive diathermy therapy. Diathermy is the passage of radiowaves through the tissue to heat it, and is used as a physical therapy for muscle pain and other applications. Diathermy poses a risk of death in a patient with DBS electrodes.

Patients who are cognitively impaired may become more so after surgery, and cognitive impairment usually prevents a patient from undergoing surgery.

Normal results

Deep brain stimulation improves the movement disorder symptoms of Parkinson’s disease by 25-75%,

QUESTIONS TO ASK THE DOCTOR

• How many electrode implantations has the neurosurgeon performed?
• What is his own rate of serious complications?
• Would pallidotomy be appropriate for me?
• How will my medications change after the operation?

depending on the care of the placement and the ability to find the optimum settings. These improvements are seen most while off levodopa; DBS does little to improve the best response to levodopa treatment. Lev-odopa dose will likely be reduced, leading to a significant reduction in dyskinesias.

Morbidity and mortality rates

The rate of complications depends highly on the skill and experience of the surgical team performing the procedure. Rates from one of the most experienced teams, in a study of over 200 patients, were as follows.

Post-operative complications:

• asymptomatic intracranial bleed (10% of procedures)
• symptomatic intracranial bleed (2%)
• seizures (3%)
• headache (25%)
• infection (6%)

Device-related complications:

• lead replacements (9%)
• lead repositionings (8%)
• extension wire replacements (6%)
• implantable pulse generator replacements (17%), approximately half of which were due to malfunction

The risk of death is less than 1%.

Alternatives

Patients who are candidates for deep brain stimulation have usually been judged to require surgery for effective treatment of their symptoms. Other surgical alternatives for Parkinson’s disease include pallidotomy and thalamotomy, which destroy brain tissue to achieve the same effect as the stimulation. Pallidotomy is rarely performed for Parkinson’s disease, unless tremor is the only debilitating symptom. It is common in essential tremor. DBS for dystonia is the only really promising neurosurgical treatment for this condition. Some peripheral surgeries may be appropriate for selected patients.

Resources

BOOKS

Jahanshahi, M., and C. D. Marsden. Parkinson’s Disease: A Self-Help Guide. New York: Demos Medical Press, 2000.

ORGANIZATIONS

National Parkinson’s Disease Foundation. Bob Hope Parkinson Research Center, 1501 N.W. 9th Avenue, Bob Hope Road, Miami, FL 33136-1494. (305) 547-6666. (800) 327-4545. Fax: (305) 243-4403. http://www.parkinson.org.

WE MOVE, Worldwide Education and Awareness for Movement Disorders. 204 West 84th Street, New York, NY 10024. (800) 437-MOV2, Fax: (212) 875-8389. http://www.wemove.org.

Richard Robinson

Chitra Venkatasubramanian

Deep vein thrombosis seeVenous thrombosis prevention

Deep brain stimulation

Definition

Deep brain stimulation (DBS) delivers a constant low electrical stimulation to a small region of the brain, through implanted electrodes connected to an implanted battery. It is used to partially restore normal movements in Parkinson's disease, essential tremor, and dystonia.

Purpose

Parkinson's disease is due to degeneration of a group of cells called the substantia nigra. These cells interact with other brain regions to help control movement. The normal signals from the substantia nigra inhibit these other regions, and so when it degenerates, these regions become overactive. The electrical signals from the DBS electrodes mimic the inhibitory function of the substantia nigra, helping to restore more normal movements.

The substantia nigra normally releases the chemical dopamine, which exerts its inhibitory action on the globus pallidus interna (GPi) and the subthalamic nucleus (STN). For Parkinson's disease, deep brain stimulation is performed on these two centers. The target for DBS in dystonia is the GPi as well. Treatment of essential tremor usually targets the thalamus.

Each of these brain regions has two halves, which control movement on the opposite side of the body: right controls left, and left controls right. Unilateral DBS may be used if the symptoms are much more severe on one side. Bilateral DBS is used to treat symptoms on both sides.

Demographics

Parkinson's disease affects approximately one million Americans. The peak incidence is approximately age 62, but young-onset PD can occur as early as age 40. Because young-onset patients live with their disease for so many more years, they are more likely to become candidates for surgery than older-onset patients. In addition, younger patients tend to do better and have fewer adverse effects of surgery. Approximately 5% of older PD patients receive one form or another of PD surgery. Many more develop the symptoms for which surgery may be effective, but either develop them at an advanced age, making surgery inadvisable, or decide the risks of surgery are not worth the potential benefit, or do not choose surgery for some other reason.

Essential tremor is more common than Parkinson's disease, but rarely becomes severe enough to require surgery. Dystonia is a very rare condition, and the number of patients who have received DBS as of 2003 is under 100.

Description

Deep brain stimulation relies on implanting a long thin electrode deep into the brain, through a hole in the top of the skull. In order to precisely locate the target area and to ensure the probe is precisely placed in the target, a "stereotactic frame" is used. This device is a rigid frame attached to the patient's head, providing an immobile three-dimensional coordinate system, which can be used to precisely track the location of the GPi or STN and the movement of the electrode.

For unilateral DBS, a single "burr hole" is made in the top of the skull. Bilateral DBS requires two holes. A strong topical anesthetic is used to numb the skin while this hole is drilled. Since there are no pain receptors in the brain, there is no need for deeper anesthetic. In addition, the patient must remain awake in order to report any sensory changes during the surgery. The electrode is placed very close to several important brain structures. Sensory changes during electrode placement may indicate the electrode is too close to one or more of these regions.

Once the burr hole is made, the surgeon inserts the electrode. Small electric currents from the electrode are used to more precisely locate the target. This is harmless, but may cause twitching, light flashes, or other sensations. A contrast dye may also be injected into the spinal fluid, which allows the surgeon to visualize the brain's structure using one or more imaging techniques. The patient will be asked to make various movements to assist in determining the location of the electrode.

The electrode is connected by a wire to an implanted pulse generator. This wire is placed under the scalp and skin. A small incision is made in the area of the collarbone, and the pulse generator is placed there. This portion of the procedure is performed under general anesthesia.

Diagnosis/Preparation

DBS for Parkinson's disease is considered as an option in a patient who is still responsive to levodopa (used to treat symptoms) but has developed motor complications. These include the rapid loss of benefit from a single dose (wearing off), unpredictable fluctuations in benefit (on-off), and uncontrolled abnormal movements (dyskinesias). Essential tremor patients who are candidates for surgery are those whose tremor is unsatisfactorily controlled by medications and whose tremor significantly impairs activities of daily living. Similar criteria apply for dystonia patients.

The patient who is a candidate for DBS discusses all the surgical options with his neurologist before deciding on deep brain stimulation. A full understanding of the risks and potential benefits must be understood before consenting to the surgery.

The patient will undergo a variety of medical tests, and one or more types of neuroimaging procedures, including MRI, CT scanning, angiography (imaging the brain's blood vessels) and ventriculography (imaging the brain's ventricles). On the day of the surgery, the stereotactic frame is fixed to the patient's head. A local anesthetic is used at the four sites where the frame's pins contact the head; there may nonetheless be some initial discomfort. A final MRI is done with the frame in place, to set the coordinates of the targeted area of the brain in relation to the frame.

The patient will receive a mild sedative to ease the anxiety of the procedure. Once the electrodes are positioned, the patient receives general anesthetic to implant the pulse generator.

Aftercare

The procedure is lengthy, and the patient will require a short hospital stay afterward to recover from the surgery. Following the procedure itself, the patient meets several times with the neurologist to adjust the stimulation. The pulse generator is programmable, and can be fine-tuned to the patient's particular needs. This can provide a higher degree of symptom relief than lesioning surgeries, but requires repeated visits to the neurologist. Pulse generator batteries must be replaced every three to five years. This is done with a small incision as an outpatient procedure. Since the generator is in the chest area, no additional brain surgery is required.

The patient's medications are adjusted after surgery, with a reduction in levodopa likely in most patients who receive DBS of the subthalamic nucleus.

Risks

Deep brain stimulation entails several risks. There are acute surgical risks, including hemorrhage and infection, and the risks of general anesthesia. The electrodes can be placed too close to other brain regions, which can lead to visual defects, speech problems, and other complications. These may be partially avoided by adjusting the stimulation settings after the procedure. Because a device is left implanted under the skin, there is the risk of breakage or malfunction, which requires surgical removal.

A patient with implanted electrodes must not receive diathermy therapy. Diathermy is the passage of radiowaves through the tissue to heat it, and is used as a physical therapy for muscle pain and other applications. Diathermy poses a risk of death in a patient with DBS electrodes.

Patients who are cognitively impaired may become more so after surgery, and cognitive impairment usually prevents a patient from undergoing surgery.

Normal results

Deep brain stimulation improves the movement disorder symptoms of Parkinson's disease by 25–75%, depending on the care of the placement and the ability to find the optimum settings. These improvements are seen most while off levodopa; DBS does little to improve the best response to levodopa treatment. Levodopa dose will likely be reduced, leading to a significant reduction in dyskinesias.

Morbidity and mortality rates

The rate of complications depends highly on the skill and experience of the surgical team performing the procedure. Rates from one of the most experienced teams, in a study of over 200 patients, were as follows.

Post-operative complications:

• asymptomatic intracranial bleed (10% of procedures)
• symptomatic intracranial bleed (2%)
• seizures (3%)
• headache (25%)
• infection (6%)

Device-related complications:

• lead replacements (9%)
• lead repositionings (8%)
• extension wire replacements (6%)
• implantable pulse generator replacements (17%), approximately half of which were due to malfunction

The risk of death is less than 1%.

Alternatives

Patients who are candidates for deep brain stimulation have usually been judged to require surgery for effective treatment of their symptoms. Other surgical alternatives for Parkinson's disease include pallidotomy and thalamotomy, which destroy brain tissue to achieve the same effect as the stimulation. Pallidotomy is rarely performed for Parkinson's disease, unless tremor is the only debilitating symptom. It is common in essential tremor. DBS for dystonia is the only really promising neurosurgical treatment for this condition. Some peripheral surgeries may be appropriate for selected patients.

Resources

books

jahanshahi, m., and c. d. marsden. parkinson's disease: a self-help guide. new york: demos medical press, 2000.

organizations

national parkinson's disease foundation. bob hope parkinson research center, 1501 n.w. 9th avenue, bob hope road, miami, fl 33136-1494. (305) 547-6666. (800) 327-4545. fax: (305) 243-4403. <http://www.parkinson.org>.

we move, worldwide education and awareness for movement disorders. 204 west 84th street, new york, ny 10024. (800) 437-mov2, fax: (212) 875-8389. <http://www.wemove.org>.

Richard Robinson

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

Deep brain stimulation is performed by a neurosurgeon in a hospital.

QUESTIONS TO ASK THE DOCTOR

• How many electrode implantations has the neurosurgeon performed?
• What is his own rate of serious complications?
• Would pallidotomy be appropriate for me?
• How will my medications change after the operation?

Deep brain stimulation

Definition

In deep brain stimulation (DBS), electrodes are implanted within the brain to deliver a continuous low electric current to the target area. The current is passed to the electrodes through a wire running under the scalp and skin to a battery-powered pulse generator implanted in the chest wall.

Purpose

DBS is used to treat Parkinson's disease (PD) and essential tremor (ET). It has also been used to treat dystonia , chronic pain , and several other conditions

The movement disorders of PD and ET are due to loss of regulation in complex circuits within the brain that control movement. While the cause of the two diseases differ, in both cases, certain parts of the brain become overactive. Surgical treatment can include destruction of part of the overactive portion, thus rebalancing the regulation within the circuit. It was discovered that the same effect could be obtained by electrically stimulating the same areas, which is presumed to shut down the cells without killing them.

DBS may be appropriate for patients with PD or ET whose symptoms are not adequately controlled by medications. In PD, this may occur after five to ten years of successful treatment. Continued disease progression leads to decreased effectiveness of the main treatment for PD, levodopa. Increasing doses are needed to control symptoms, and over time, this leads to development of unwanted movements, or dyskinesias. Successful DBS allows a reduction in levodopa, diminishing dyskinesias.

For PD, deep brain stimulation is performed on either the globus pallidus internus (GPi) or the subthalamic nucleus (STN). Treatment of essential tremor usually targets the thalamus. Each of these brain regions has two halves, which control movement on the opposite side of the body: right controls left, and left controls right. Unilateral (onesided) DBS may be used if the symptoms are much more severe on one side. Bilateral DBS is used to treat symptoms on both sides.

Precautions

DBS is major brain surgery. Bleeding is a risk, and patients with bleeding disorders or who are taking blood thinning agents may require special management. DBS leaves metal electrodes implanted in the head, and patients are advised not to undergo diathermy (tissue heating) due to the risk of severe complications or death. Diathermy is used to treat chronic pain and other conditions. Special cautions are required for patients undergoing MRI after implantation.

Description

In DBS, a long thin electrode is planted deep within the brain, through a hole in the top of the skull. To make sure the electrode is planted in the proper location, a rigid "stereotactic frame" is attached to the patient's head before surgery. This device provides a three-dimensional coordinate system, used to locate the target tissue and to track the placing of the electrodes.

A single "burr hole" is made in the top of the skull for a unilateral procedure. Two holes are made for a bilateral procedure. This requires a topical anesthetic. General anesthesia is not used, for two reasons. First, the brain does not feel any pain. Second, the patient must be awake and responsive in order to respond to the neurosurgical team as they monitor the placement of the electrode. The target structures are close to several nerve tracts that carry information throughout the brain. Abnormalities in vision, speech, or other cognitive areas may indicate that the electrode is too close to one of these regions, and thus needs repositioning.

Other procedures may be used to ensure precise placement of the electrode, including electrical recording and injection of a contrast dye into the spinal fluid. The electrical recording can cause some minor odd sensations, but is harmless.

The electrode is connected by a wire to an implanted pulse generator. This wire is placed under the scalp and skin. A small incision is made in the area of the collarbone, and the pulse generator is placed there. This portion of the procedure is performed under general anesthesia.

Preparation

A variety of medical tests are needed before the day of surgery to properly locate the target (GPi, thalamus, or STN), and fit the frame. These may include CT scans, MRI, and injection of dyes into the spinal fluid or ventricles of the brain. The frame is attached to the head on the day of surgery, which may be somewhat painful, although the pain is lessened by local anesthetic. A mild sedative is given to ease anxiety.

Aftercare

Implantation of the electrodes, wire, and pulse generator is a lengthy procedure, and the patient will require a short hospital stay afterward to recovery from the surgery. Following this, the patient will meet several times with the neurologist to adjust the stimulator settings, in order to get maximum symptomatic improvement. The batteries in the pulse generator must be replaced every three to five years. This is done with a small incision as an outpatient procedure.

The patient's medications are adjusted after surgery. Most PD patients will need less levodopa after surgery, especially those who receive DBS of the STN.

Risks

Risks from DBS include the surgical risks or hemorrhage and infection, as well as the risks of general anesthesia. Patients who are cognitively impaired may become more so after surgery. Electrodes can be placed too close to other brain regions, which can lead to visual defects, speech problems, and other complications. If these occur, they may be partially reduced by adjusting the stimulation settings. DBS leaves significant hardware in place under the skin, which can malfunction or break, requiring removal or replacement.

Normal results

Deep brain stimulation improves the movement symptoms of PD by 25–75%, depending on how carefully the electrodes are placed in the optimal target area, and how effectively the settings can be adjusted. These improvements are seen most while off levodopa; DBS does little to improve the best response to levodopa treatment. DBS does allow a reduction in levodopa dose, which usually reduces dyskinesias by 50% or more. This is especially true for DBS of the STN; DBS of the GPi may lead to a smaller reduction. Levodopa dose will likely be reduced, leading to a significant reduction in dyskinesias.

DBS in essential tremor may reduce tremor in the side opposite the electrode by up to 80%.

Resources

BOOKS

Jahanshahi, M., and C. D. Marsden. Parkinson's Disease: A Self-Help Guide. New York: Demos Medical Press, 2000.

WEBSITES

National Parkinson's Disease Foundation. (December 4, 2003). <www.npf.org>.

WE MOVE. (December 4, 2003). <www.wemove.org>.

ORGANIZATIONS

International Essential Tremor Foundation. P.O. Box 14005, Lenexa, Kansas 66285-4005. 913-341-3880 or 888-387-3667; Fax: 913-341-1296. [email protected]. <http://www.essentialtremor.org/>.

Richard Robinson