Neuromodulation in Neurosurgery
By Peter B. Weber, M.D.
Parkinson’s disease, epilepsy, stroke, dementia, dystonia, obsessive-compulsive disorder, depression, coma, and pain—these seemingly unrelated conditions share common ground in that central nervous system stimulation has been used for their treatment. Stimulation of the brain or nerves delivers therapeutic electrical activity to target zones to treat select nervous system derangements in each of these diseases. This is a rapidly expanding area of neurosurgery. In the following article we will review established, upcoming, and even some breakthrough futuristic neuromodulation technologies. These technologies will, without doubt, play some role in the treatment of neurologic conditions in the coming years.
Neuromodulation has been around for nearly 45 years. In the late 1960s Medtronic delivered implanted spinal cord stimulators for chronic pain. In 1973 Hosobuchi introduced thalamic stimulation for chronic pain. In 1987 Benabid reported on the use of deep brain stimulation of the thalamus for Parkinson’s disease (Ref 1). An advantage of brain stimulation is that this technology is scalable, reversible, and directional. Different brain regions are targeted in each of the above conditions. The electrodes can be directed to almost any area of the brain.
Stimulators used in these techniques are scalable in that the device can be programmed to a desired level of output. If the stimulation is ineffective or has deleterious effects, the device can be turned off and rendered silent without harm to the patient. This provides distinct advantages over the irreversible techniques of lesioning (e.g., thalamotomy).
Vagus nerve stimulation for epilepsy has been available since 1988. Spinal cord stimulation for chronic pain and spasticity has been around for approximately 40 years. These are accepted proven technologies that have a role in their respective disease of epilepsy and chronic pain. The field of neuromodulation is broad and includes these and other technologies. CPMC offers many types of neuromodulation techniques for a wide variety of conditions. This article’s focus is on deep brain stimulation neuromodulation techniques.
One million Americans suffer from Parkinson’s disease. After years of treatment with Best Medical Therapy (BMT), a percentage of patients will deteriorate and medications, such as Sinemet, will need to be taken in higher doses and more frequently. As the medication dose escalates, medication side effects, such as dyskinesias, will amplify. The therapeutic window for effective treatment with these medications narrows to the point where patients may have only a few hours of “on” time and spend the rest of the day in “off” time or suffering from severe dyskinesias (see figure 1).
Stimulation of deep brain areas is an accepted modality used to ameliorate some of the deleterious consequences of late Parkinson’s disease. For those late-stage patients who initially responded to dopamine agonists, who are spared from significant dementia, and who are in good medical condition, surgery can be contemplated to improve quality of life and maintain independence. With stimulation of structures such as the subthalamic nucleus, 60% to 80% of patients will achieve improvement in “on” time, two-thirds will have improved motor scores, and two-thirds will have an opportunity to reduce medications (Ref 2). No surgery is risk-free, and deep brain stimulation carries its own burden of potential complications. Yet, when compared to the severe disability of late-stage Parkinson’s disease, these risks are acceptable.
Bilateral deep brain stimulation of the subthalamic nuclei for late-stage Parkinson’s disease has been proven effective in randomized trials when compared to BMT (Ref 3). Stimulation of other brain areas, such as the globus pallidus interna, is also effective (Ref 4). Investigations into alternative target areas such as the zona incerta are forthcoming. Questions such as when or how early to intervene in the disease processes are being addressed at this time. Should we apply this technology before significant disability has occurred and before the medications have lost their effectiveness? We hope to have these answers soon.
The same techniques of implantation of electrodes into deep brain structures can also be applied to essential tremor. Essential tremor is an inherited condition that affects motor control. Though many cases respond to medications, other patients fail to respond or deteriorate to a point where the "intention tremor" affects their ability to function independently. The deep brain electrodes are placed in a different location than in Parkinson’s disease. The target for the electrodes in the essential tremor patient is instead the thalamus. Bilateral electrodes are usually necessary. The device is implanted during an "awake" surgery. Significant improvement in tremor may be obtained in 70% to 80% of patients.
Dystonias are repetitive twisting involuntary muscle contractions. Such dramatic involuntary muscular movements or postural contortions can be severely disabling. Recent publications give new hope to the old problem of severe dystonia. Successful treatment of dystonias with deep brain stimulation has been reported (Ref 5). Primary generalized dystonia (for example, the DYT1 mutation variety) and segmental dystonias have responded to this therapeutic modality.
Epilepsy affects 1% to 2% of the population. One third of these patients will not achieve seizure control and will remain refractory despite trials of alternative seizure medications or combinations of medications. Surgery to resect areas of the brain to control seizures is an accepted, tested, highly successful modality that has been offered since the 1950s. Unfortunately, only one-third of "refractory" patients will be candidates for resection procedures. Brain stimulation has evolved as a new modality that can be considered for patients when medications have failed and resection of epileptic brain areas is not an option. Two recent multicenter randomized studies have addressed the concepts of brain stimulation for refractory epilepsy—the Sante study and the NeuroPace study.
Stimulation of deep thalamic regions is theorized to reduce the potential for seizures to occur. In the Sante study (Ref 6) more than half of the patients achieved significant reduction in seizure frequency and severity, and 13% were rendered seizure-free. These patients were refractory to medical management and were deemed not to be candidates for other types of seizure surgery. In essence, they had no other good alternatives. Deep brain stimulation was effective for some, and perhaps further analyses will help delineate which subcategories of medically refractory epilepsy patients would be most likely to benefit from thalamic stimulation.
Miniaturization of computer technology has evolved to allow doctors to implant an EEG (brainwave) recording device in the same apparatus as a deep brain stimulator (see figure 2). The concept would allow for tailored stimulation that would respond to abnormal discharges in the brain. At other times, the device would remain silent and conserve battery life. If the site of onset of seizures within the brain could be localized, the lead wires of this device could be placed over that area. The "responsive neural stimulation system" would record brain activity, detect (by computer algorithms) abnormal activity, and automatically stimulate that area of the brain to try to abort the abnormal electrical activity (see figure 3). This fully self-contained implantable system was recently investigated in the NeuroPace trial (awaiting publication). Of the 191 patients enrolled, more than 50% responded and complication rates were low. CPMC and its comprehensive epilepsy care team participated in this trial and CPMC now has the largest clinical experience with this device of any facility.
Cortical Stimulation for Stroke
Early treatment of ischemic stroke by techniques to return blood flow to deprived areas has improved the prognosis for this condition. But for patients with completed stroke, there has been little more than time and rehabilitation therapies. Recent trials have investigated the possibility of implanted electrodes for cortical stimulation of affected brain areas. Though initial results were promising, larger-scale randomized studies failed to demonstrate significant benefits of cortical stimulation with implanted electrodes over standard rehabilitation (Ref 7). These negative results should be used to guide future investigations as complete abandonment of cortical stimulation for stroke would be premature. Perhaps by better targeting, improved imaging, and more precise patient selection the population that would be most likely to succeed could be offered more appropriate and tailored therapies of this nature.
Deep Brain Stimulation for Obsessive-Compulsive Disorder, Chronic Pain, Narcotic Addiction, and Depression
Deep brain stimulation technologies are now reaching into some of the most challenging neurologic conditions like narcotic addiction, depression, obsessive-compulsive disorder (OCD), and chronic pain. In OCD, for example, success has been achieved in a few carefully selected severe cases. There are cases of OCD so severe that normal everyday activities and interpersonal interactions are impossible. The condition has been shown to be treatable by stimulating frontal brain areas with implanted permanent electrodes. As in each of the other areas mentioned above, there are successes and failures. But the ability to return someone to a functional state and avoid institutionalization is a reachable goal that encourages neurosurgeons to look for better solutions from neuromodulation tools such as deep brain stimulation.
Deep brain stimulation is a form of neuromodulation. The disease process dictates the type of stimulation and location of electrodes. Many brain conditions can be characterized by dysfunction of a region or system. If stimulation for enhancement of or electrical blockade of this region or system would assist the patient, then techniques of neuromodulation may be appropriate. Proven success for deep brain stimulation exists in the areas of epilepsy, Parkinson’s disease, dystonia, and essential tremor. New data are emerging in the fields of psychiatric disorders, dementia, stroke, and other conditions to suggest that deep brain stimulation may play a role as adjunctive modality. This is an exciting area of medicine that truly characterizes a forefront of our abilities. CPMC and the CPNI physicians are proud to be a part of this developing area and are available to assist in the management of these difficult problems.
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