Deep brain stimulation (DBS) is now considered the neurosurgical therapy of choice for movement disorders, with over 80,000 patients having undergone DBS worldwide.¹ DBS works through the delivery of therapeutic electrical energy to highly specific targets in the brain. The safety and efficacy of DBS have been validated in many high-quality studies in over 20 years of use. DBS is also the subject of intense intellectual study; a recent PubMed search for “deep brain stimulation” returned over 3500 published studies.² A particularly exciting aspect of the ongoing research in DBS is evaluation of expanding indications for the therapy, which span neuropsychiatric disorders, epilepsy, and disorders of consciousness, among others. This chapter reviews the historical underpinnings of DBS, indications for use, and future horizons. Additionally, a brief description of DBS components and purported mechanisms of action will be provided.

Historical Beginnings

The modern era of deep brain stimulation has its historical roots in the development of stereotactic surgery, which has its own origins in the work of the French mathematician and philosopher René Descartes. In part II of his 1637 work, Discourse on the Method, Descartes describes a method for specifying the location of a point based on its relationship to two intersecting axes.³ (Of note, this work is best known for its famous quotation, “Je pense, donc je suis” [I think, therefore I am], which occurs in part IV.) This method, known as the Cartesian coordinate system, facilitated the development of calculus by Isaac Newton and Gottfried Wilhelm Leibniz as well as modern stereotactic neurosurgery.

The happy marriage of the fields of stereotaxy, movement disorder surgery, and psychosurgery gave rise to the underlying principles of modern DBS surgery. On the movement disorders front, much work had been done on cortical resections and subcortical lesioning to palliate these disorders. In 1909, Sir Victor Horsley, who described the first stereotactic apparatus in animals, relieved hemiathetosis in a 15-year-old boy by removing the precentral gyrus somatotopically associated with the upper extremity.⁴ In 1931, Bucy performed the same procedure for seizure relief and relieved the patient’s choreoathetosis in the process.⁵ He later, in 1937, performed this procedure with Theodore Case for the treatment of post-traumatic tremor.⁶ These patients had postoperative hemiparesis and dyspraxia that resolved to a great extent postoperatively.⁷ In 1931, Putnam began sectioning of the extrapyramidal tracts in the high cervical cord, with good results for choreoathetosis but not with parkinsonian tremor.^8,⁹ Given that cortical ablation would relieve tremor, but extrapyramidal ablation would not, he reasoned that impulses in the pyramidal tract were responsible for the production of parkinsonian tremor, and in 1940, he reported the results of lateral pyramidotomy in the high cervical region in seven patients.¹⁰ Again, these patients had postoperative improvement of tremor but some resultant hemiplegia.

The search for a suitable procedure to maximize tremor control yet minimize postoperative morbidity led to cerebral pedunculotomy by Walker;¹¹ open, transcortical, transventricular removal of portions of the basal ganglia by Meyers;¹² and anterior choroidal artery ligation by Cooper.¹³^–¹⁵ (As an aside, Cooper’s procedure was discovered accidentally when he tore the anterior choroidal artery during an aborted cerebral pedunculotomy.) These procedures, while therapeutic, were both variable in their outcomes and suffered from high perioperative morbidity rates, thereby necessitating more precise and less invasive targeting.

Furthermore, proponents of psychosurgery wanted a means for performing controlled prefrontal lobotomy.¹⁶ In the 1940s, there was concern among neurosurgeons regarding the high morbidity and mortality rates associated with open psychosurgical procedures including prefrontal leucotomy as introduced by Egas Moniz and prefrontal lobotomy as introduced by Walther Freeman and James Watts.¹⁷ There was a general feeling that the principles of psychosurgery were sound, but smaller and more specific structures should be targeted to achieve optimal therapeutic benefit while avoiding unnecessary morbidity and unwanted neurological deficit.

Initial attempts of stereotactic surgery began in the late nineteenth and early twentieth centuries. In 1889, D.N. Zernov, a Russian surgeon in Moscow, used a navigation system (called an encephalometer) based on polar coordinates and referenced to external landmarks to drain a cerebral abscess.^18,¹⁹ The first truly modern stereotactic apparatus based on Cartesian coordinates and based on internal cerebral landmarks was first described in animals in the early part of the twentieth century by Sir Victor Horsley and Robert Clarke. In 1908, they described a stereotactic apparatus that could introduce a probe into subcortical structures defined in a Cartesian coordinate system.²⁰

The first device developed for inserting an electrode accurately into a chosen structure in the human brain was described by Ernest A. Spiegel, Henry T. Wycis, and others in 1947 ²¹ (Fig. 53.1). At that time, cerebral anatomical structures were targeted based on location relative to the third ventricle using ventriculogram x-rays. Electrode position in the apparatus of Spiegel and Wycis was adjusted by sliding the carrier along a base plate in the anteroposterior and lateral directions, with vertical adjustments made by a microdrive. Leksell introduced a semicircular arc apparatus in 1949, allowing for the introduction of an electode to a target along any trajectory, because the target now would lie in the center of the arc²² (Fig. 53.2).

FIGURE 53.1 Spiegel (on left of shielding cage) and Wycis (standing) in the operating room, using their stereotactic apparatus. The cage seen is a grounded copper cage to shield electrode recording from ambient interference.

FIGURE 53.2 Lars Leksell with his stereotactic arc. With this system, the target can be approached from any angle because it uses a center-of-arc principle. The basic components are the Cartesian coordinate frame, which is attached to the patient’s head using four pins, and the semicircular arc.

(Reproduced with permission of Elekta AB, Stockholm, Sweden.)

The first lesioning procedures performed by Spiegel and Wycis were in the dorsomedial thalamic nucleus for agitation and psychosis, the medial thalamus for epilepsy, and mesencephalic pain pathways for intractable pain.^7,²³ With the advent of stereotactic lesioning procedures, many new techniques were developed for the management of psychiatric and movement disorders. These included pallidotomy and thalamotomy for the relief of Parkinson’s disease (PD)–associated tremor,²⁴^–²⁹ as well as anterior cingulotomy,^30,³¹ anterior capsulotomy,³² subcaudate tractotomy,³³ and limbic leucotomy³⁴ in the treatment of affective disorders^7,^17,^35,³⁶ Fig. 53.3. However, with the advent of L-dopa in the 1960s for PD, there was a steep decrease in surgery for PD.³⁷ Similarly, the introduction of lithium in the late 1940s and the antipsychotic drug chlorpromazine in the mid-1950s led to a nonsurgical bend in the management of psychiatric disorders.^17,^36,³⁸ Therefore, the next paradigm shift in the treatment of these disorders did not come until the limitations of these medications with their side effects and lack of sustained benefits were realized, and DBS provided a safer, nondestructive, reversible, and adjustable approach for the treatment of these disorders.

FIGURE 53.3 Classical drawing depicting locations of stereotactic lesioning procedures for psychosurgery.

(Reprinted from Sweet WH. Treatment of medically intractable mental disease by limited frontal leucotomy—justifiable? N Engl J Med. 1973;289(21):1117-1125; used with permission of the Massachusetts Medical Society.)

In 1809, Rolando first demonstrated that electrical impulses could modify the function of brain regions, and prior to that, Aldini attempted stimulation of the brains of criminals immediately following their executions.^37,³⁹ Hassler found, during stereotactic exploration of the brain for pallidotomy, that low-frequency stimulation would worsen tremor and high-frequency stimulation would ameliorate it.^37,⁴⁰ This was first put into practice in 1967 by Bechtereva and associates with chronic DBS of the thalamus, striatum, and pallidum for the treatment of movement disorders.⁴¹

It was not until the 1970s and 1980s, however, that the modern era of chronic stimulation was ushered in. Hosobuchi and co-workers reported on stimulation of the VPM thalamus for the control of facial anesthesia dolorosa following rhizotomy for trigeminal neuralgia in 1973.⁴² DBS of ventral periaqueductal gray matter in the midbrain for the treatment of cancer pain was reported by Richardson and Akil in the mid-1970s.⁴³ Chronic DBS for the management of movement disorders was utilized by several groups including Benabid and colleagues,^44,⁴⁵ Blond and Siegfried,⁴⁶ Siegfried and Shulman,⁴⁷ and Brice and McLellan.⁴⁸ DBS has similar efficacy to its corresponding lesioning procedures, but with an improved safety profile, inherent reversibility, and adjustment of the stimulation parameters over time to accommodate the patient’s needs. These factors have led to DBS being adopted as the neurosurgical standard of care for movement disorders as well as the expansion of DBS to the treatment of epilepsy, psychiatric disorders including obsessive-compulsive disorder (OCD) and depression, as well as chronic pain, Tourette’s syndrome, and even disorders of consciousness and addiction.

Basic Neurocircuitry Principles

Parallel cortico-striato-pallido-thalamo-cortical (CSPTC) circuits exist for limbic, associative, and motor function.⁴⁹ The motor loop is the most commonly described loop and is important in the pathogenesis of PD and the therapeutic efficacy of DBS in this condition.³⁷ Limbic and associative circuits have been implicated in the pathogenesis of neuropsychiatric conditions including OCD and major depressive disorder (MDD), which respond to DBS of critical nodes along the circuit, including the ventral capsule/ventral striatum (VC/VS), anterior limb of the internal capsule (ALIC), nucleus accumbens (NAc), subgenual cingulate cortex (SCC), and inferior thalamic peduncle.⁴⁹^–⁶¹ These circuits maintain some degree of topographic segregation, with motor circuitry more dorsolateral, limbic circuitry ventromedial, and associative circuitry in between.⁶²

These circuits are not strictly “parallel.” Haber and associates demonstrated some interface between these circuits in primates with the more medial limbic circuits ultimately influencing more dorsolateral motor circuits.⁶² This unique arrangement allows for a link between emotion and motivation (limbic circuits) with cognition and planning (associative circuits), which finally manifests with a motor output and behavior (motor circuits).

Both direct and indirect loops exist for the associative and limbic circuits, as they do for the motor circuits.⁴⁹ The direct loops connect from the striatum to the globus pallidus pars interna (GPi), substantia nigra pars reticulata (SNr), and ventral tegmental area (VTA). From there, the projections head to the thalamus. Indirect loops connect from the striatum to the globus pallidus pars externa (GPe), and then head to the subthalamic nucleus (STN) before going to the GPi, SNr, and VTA (Fig. 53.4).

FIGURE 53.4 Schematic of relevant cortico-striato-pallido-thalamo-cortical (CSPTC) neural circuitry.

In choosing an appropriate target for neuromodulation by DBS, it is important to note that multiple targets can be efficacious for a single disease. For example, we know that PD responds well to DBS of the GPi and subthalamic nucleus.^37,⁶³ In psychosurgery, multiple targets have been used, for example, in OCD including the ALIC,^52,⁵⁹ VC/VS and NAc,^51,⁵⁷ inferior thalamic peduncle,⁵⁶ and subthalamic nucleus.⁵⁸ This is likely secondary to the rich connectivity of the modulated circuits and the mechanism of action of DBS. High-frequency stimulation (HFS) has a net inhibitory effect and low-frequency stimulation (LFS) has a net excitatory effect; however, the mechanism of DBS (high-frequency) is likely more complex with activation of nearby axons and suppression of abnormal impulses through the circuits involved.³⁷

Deep Brain Stimulation Surgery: Indications, Target, and Outcomes

DBS surgery for movement and other disorders should be planned and managed in the context of a multidisciplinary team consisting of the neurosurgeon, movement disorder neurologist, psychiatrist, neuropsychologist, neurophysiologist, and physician extenders such as nurse practitioners and physician assistants. Accurate diagnosis of the specific movement disorder or neuropsychiatric disorder by a movement disorder neurologist or a psychiatrist, respectively, is an essential first step, because success of the procedure significantly depends upon selecting the appropriate patient. Following accurate diagnosis, risk-benefit analysis of intervention for each individual patient should be performed. In general, patients to be considered for DBS should have significant disability in the performance of activities of daily living, despite adequate maximal medical therapy and, in the case of neurobehavioral disorders, adequate cognitive therapy.

Candidates for DBS should be healthy enough to undergo surgery and should be optimized with respect to other medical conditions including any heart disease, hypertension, or diabetes. Patients receiving anticoagulation should be able to tolerate stoppage of these medications for a period before and after surgery. Patients should also have the mental fortitude and physical stamina to undergo a lengthy procedure awake and immobilized in a stereotactic frame while providing feedback during microstimulation during the DBS procedure. Mental agility and physical stamina are also important in the postoperative period as stimulator programming may require prolonged sessions.

From a social standpoint, the patient must be able to tolerate the psychosocial demands of surgery, be compliant with medication changes and postoperative care, and have a strong support network in place. These patients need to be willing to commit time and personal resources for medication and programming adjustments. In addition, patients need to understand the risks and benefits, and have realistic expectations of surgery. Importantly, patients and families need to understand that DBS is not a curative procedure but rather one aimed at improving quality of life.

All patients should undergo detailed neuropsychological assessment. The aim is to identify patients who have underlying cognitive deficits or psychiatric conditions that may be worsened by DBS. Severe dementia or cognitive impairment is generally a contraindication to DBS, and patients with even mild deficits in frontal executive function or cognition need especially strong social support following surgery. Psychiatric conditions as depression, mania, and anxiety should be identified and optimized preoperatively, and patients with psychosis or personality disorders should generally be excluded from surgical intervention.³⁷ These factors underscore the importance of a multidisciplinary team devoted to the care of DBS patients. (Selection criteria are summarized in Table 53.1.)

TABLE 53.1 General Principles of Patient Selection in Deep Brain Stimulation Surgery: Predictors of Successful Outcome

Accurate diagnosis of the specific movement disorder or neuropsychiatric disorder by a movement disorder neurologist or a psychiatrist

In Parkinson’s disease, evidence of levodopa responsiveness: 30% improvement of the Unified Parkinson’s Disease Rating Scale (Part III) except in tremor-predominant disease)

Absence of underlying cognitive deficits or psychiatric conditions that may be worsened by deep brain stimulation

Realistic expectations from patient, family, and caregivers

Strong social support networks from patient’s family and caregivers

The relevance of age to outcomes following DBS is still debated. However, advanced age is associated with higher incidence of postoperative cognitive changes and higher overall risk of surgical complications. An age cutoff point for patients, however, is not recommended, and decisions should be individualized. Older patients may benefit from staged procedures to maximize recovery. Finally, patients benefit from a strong social support network from their family and caregivers. The patient and family need to have realistic expectations about surgical outcome, potential complications, and the multiple steps involved in the preoperative assessments, surgery, and perioperative and follow-up care, including stimulator programming.

Surgical Technique

Preoperative Imaging and Planning

The specific steps in the surgical technique for DBS vary depending on local practices. However, stereotactic principles firmly underlie each approach. The main aspects of the DBS placement are stereotactic anatomical targeting, physiological verification of the target, implantation of the DBS lead, and implantable pulse generator (IPG) placement. The various components may be performed in the same operative session or may be staged.

Stereotactic anatomical targeting may be by indirect or direct methods. Indirect targeting utilizes stereotactic atlases based on cadaveric sections. Known distances of the different nuclei from the midcommissural point (MCP), the halfway distance between the anterior commissure (AC) and posterior commissure (PC), are used in determining the position of the anatomical target. Typical anatomical coordinates for the common targets are as follows: STN (10-13 mm lateral to midline, 3-5 mm ventral to the AC-PC plane, and 2-4 mm posterior to the MCP), the GPi (19-21 mm lateral to the midline, 2-3 mm anterior to the MCP, and 4-5 mm ventral to the AC-PC plane), the ventralis intermedius (VIM) (11-12 mm lateral to the wall of the third ventricle, at the level of the AC-PC plane and between 2⁄12 and 3⁄12 of the AC-PC distance anterior to the PC). Table 53.2 shows the typical stereotactic targets for different indications as well as their stereotactic locations with reference to the AC, PC, and MCP.

TABLE 53.2 Deep Brain Stimulation Surgery: Targets, Indications, and Relationship to Anterior Commissure–Posterior Commissure (AC-PC) Line

Target	Indication	Anatomical Coordinates^∗
STN	Parkinson’s disease	11-13 mm lateral to midline 4-5 mm ventral to the AC-PC plane 3-4 mm posterior to the MCP
GPi	Dystonia	19-21 mm lateral to the midline 2-3 mm anterior to the MCP 4-5 mm ventral to the AC-PC plane
VIM	Essential tremor	11-12 mm lateral to the wall of the third ventricle At the level of the AC-PC plane Between 2⁄12 and 3⁄12 of the AC-PC distance anterior to the PC

GPi, globus pallidus interna; MCP, midcommissural point; STN, subthalamic nucleus; VIM, ventralis intermedius nucleus of the thalamus.

∗ Relationship to AC-PC line and MCP.

Direct targeting involves direct visualization of the deep nuclei using magnetic resonance imaging (MRI). Although computed tomography (CT) can be used in stereotactic targeting, it is difficult to visualize the various target nuclei or the AC and PC using CT alone. On the other hand, MRI offers multiplanar imaging capabilities with excellent anatomical delineation. The AC and PC can be identified on T1-weighted images while the STN can be identified on T2-weighted images (Fig. 53.5). The MRI studies may then be merged with stereotactically acquired CT images. The evident advantage of direct targeting is that discrete anatomical variation between individuals is taken into account because it is based on the individual’s anatomy as obtained from imaging. Generally, a combination of indirect and direct targeting methods is used. Following the targeting, localization of the target within the stereotactic space may be performed by frame-based or frameless systems.

FIGURE 53.5 Subthalamic nucleus (STN) on magnetic resonance imaging (MRI). High-resolution axial (A) and coronal (B) T2-weighted MRI scans. The STN is located anterosuperolateral to the substantia nigra pars reticulata (SNR) and red nucleus (RN).

(Reprinted with permission from Rezai AR, Machado AG, Deogaonkar M, et al. Surgery for movement disorders. Neurosurgery 2008;62(Suppl 2):809-838.)

A variety of stereotactic head frames are available. Figure 53.2 shows the Leksell stereotactic head frame (Elekta, Stockholm, Sweden) that is used in our institution, and Figure 53.6 shows a frameless system. The accuracy of the various systems has been demonstrated in previous studies, and the use of any system depends on surgeon preference, familiarity, and what is available in a particular institution. In addition to stereotactic anatomical targeting, imaging is also used to plan an entry point and trajectory to the target. The entry point and trajectory are chosen with the aim of avoiding cortical, subcortical, and periventricular blood vessels, thus reducing the risk of hemorrhagic complications. Contrast-enhanced T1-weighted MRI or contrast-enhanced CT scans help to delineate vessels along the electrode path and assist with vessel avoidance during planning.

FIGURE 53.6 Intraoperative image of frameless stereotactic systems. Depicted are the Nexframe and Nexdrive (Medtronic, Minneapolis, MN). Nexframe is a disposable device that fits over the Navigus Stimloc base (Medtronic) and allows deep brain stimulation (DBS) procedures to be performed without a stereotactic head frame. Once Nexframe is aligned with the intended trajectory using image guidance software, it functions as a stable cranium-mounted guide for the introduction of the DBS lead. On the top is a disposable microdrive that also acts as a simplified interface for microelectrode recording (MER) and is used for MER and final implantation of DBS electrodes.

(Reprinted with permission from Rezai AR, Machado AG, Deogaonkar M, et al. Surgery for movement disorders. Neurosurgery 2008;62(Suppl 2):809-838.)

Surgical Procedure

The stereotactic frame is placed (Fig. 53.7) and the patient is positioned supine with the stereotactic head frame fixed to the operating room table after acquisition of a stereotactic CT scan. Typically, the stereotactic CT scan is then merged with the previously acquired MRI scan and the stereotactic coordinates are obtained. The stereotactic coordinates are set on the frame and used to determine the site for skin incision and bur hole based on earlier entry point and trajectory planning. Generally in the planning, a bur hole and entry point anterior to the coronal suture are chosen. After the bur hole is performed, the dura is opened and pia coagulated for corticotomy. The microelectrodes are then inserted with the tip of the electrode placed at a defined offset above the target. At this time microelectrode recording (MER) is commenced as the electrodes are advanced in sub-millimeter steps. All sedation should be stopped before the commencement of microelectrode recording as the sedation may affect the electrophysiological mapping. MER allows for definition and verification of the physiological target. The frequency and pattern of activity of the various nuclei and white matter tracts encountered in the path to the physiological target are noted and may help determine the relationship of the trajectory to the target. These characteristic electrophysiological signatures of the targeted nuclei help confirm the physiological target. Macrostimulation is then performed to determine benefits and side effects of the stimulation.

FIGURE 53.7 Method for stereotactic head frame placement. The frame placement is performed under local anesthesia with sedation with the patient in the sitting position. The frame should be placed parallel to a line extending from the lateral canthus to the tragus (orbitomeatal line depicted in red) to approximate the plane of the anterior commissure-posterior commissure (AC-PC) line.

(Reprinted with permission from Rezai AR, Machado AG, Deogaonkar M, et al. Surgery for movement disorders. Neurosurgery 2008;62(Suppl 2):809-838.)

The main components of the DBS system are an intracranial electrode and an implantable pulse generator, by an extension wire (Fig. 53.8). After the physiological target is confirmed, the electrode is implanted at the target. The two currently available electrodes are the Medtronic 3389, which spans 7.5 mm, and the 3387, which spans 10.5 mm (each model has four contacts which are 1.5 mm in height with 0.5-mm spacing between the contacts in the 3389 and 1.5-mm spacing in the 3387 model) (Fig. 53.9). The implantation can be confirmed by fluoroscopy. After the implantation, intraoperative stimulation is then performed with the DBS lead to assess for clinical improvements and side effects of stimulation.

FIGURE 53.8 Depiction of a patient with two intracranial electrodes and a single dual-channel implantable pulse generator (IPG).

(Reproduced with permission of Medtronic, Minneapolis, MN.)

FIGURE 53.9 Axial noncontrast computed tomography (CT) scans showing intracerebral hemorrhage following placement of a deep brain stimulation (DBS) electrode. A, Thalamic hemorrhage at the target site. B, Periventricular hemorrhage with intraventricular extension.

(Reprinted with permission from Rezai AR, Machado AG, Deogaonkar M, et al. Surgery for movement disorders. Neurosurgery 2008;62(Suppl 2):809-838.)

Following implantation of the DBS electrode, it is affixed to the skull using anchoring devices such as the Navigus Stimloc device or the Medtronic bur hole ring and cap. Other institutions use bone cement or plates to secure the electrode. The distal tip of the electrode is covered by a connector or plug to protect the contacts and the electrode wire is buried in the subgaleal space for use at the time of the implantation of the pulse generator.

The implantation of the pulse generator can be performed on the same day of the implantation of the DBS lead or at a later date. The patient is placed supine and the head is turned to the side opposite the intended side of the pulse generator implantation. An infraclavicular incision is made and a subcutaneous pocket is fashioned. Occasionally, a pocket is created below the pectoralis fascia and the IPG is buried in this pocket. The advantage of this latter site is that there is less chance of downward migration and drift of the IPG with time compared to locations within a subcutaneous pocket. Other locations may be used for the placement of the IPG to accommodate variations in body habitus and for cosmetic reasons. Available IPGs include single-channel, dual-channel, rechargeable, and nonrechargeable devices. These devices can be programmed transcutaneously with a handheld module. Typical parameters that can be adjusted include voltage, pulse width, frequency, and electrode polarity.

Complications

Complications associated with DBS may be related to the surgical implantation process, related to the hardware/device, or linked to stimulation. The most serious potential complication associated with DBS electrode implantation is intracranial hemorrhage (ICH), which may result in profound neurological deficits and even death (see Fig. 53.9). ICH is reported to occur between 0.2% and 12.5% of the time.³⁷ Asymptomatic hemorrhage is more common than symptomatic cases and is detected only incidentally on postoperative brain CT imaging. In any case, intracerebral hemorrhage is usually related to direct damage to an arterial blood vessel. Occasionally, it may be due to injury to a cortical draining vein when it may present in a delayed manner with venous infarction. Careful preoperative planning of the entry point and trajectory of approach to the target that avoids evident cortical, subcortical, or periventricular blood vessels on a contrast-enhanced brain MRI scan is a first step in avoiding hemorrhagic complications. Other strategies to prevent intracerebral hemorrhagic complications include tight intraprocedural blood pressure control (maintenance of systolic blood pressure below 130 mm Hg), prevention of entry of large amounts of intracranial air by filling the subdural space with saline and occluding the bur hole with Gelfoam and tissue glue during microelectrode recording, avoiding repeated coughing or sneezing during the procedure, and avoiding the coagulation of cortical veins. There may also be increased risk of hemorrhage based on the choice of target. For example, the GPi is reported to have higher hemorrhage rates than the STN. Binder and co-workers showed a 7% risk of hemorrhage in targeting the GPi versus a 2.2% risk in targeting the STN.⁶⁴ The DBS study group reported a 9.8% risk of hemorrhage in the GPi versus 2.9% risk in the STN.⁶⁵

Elderly patients may develop transient episodes of confusion and agitation following DBS, especially with procedures. Staging of bilateral DBS procedures in these elderly patients may reduce the incidence of this complication. Infection of the hardware is an ever-present risk in these procedures. Risk of infection ranges between 1% and 15% in published studies, and most commonly affects the site of the IPG.³⁷ The risk of infection may be reduced by adhering strictly to aseptic principles during the procedure as well as the judicious use of prophylactic antibiotics. Treatment of the infection may require removal of the DBS hardware and use of appropriate antibiotics. For superficial incisional site infections in which there is no evidence of direct hardware involvement, the patient may be treated only with the exhibition of appropriate antibiotics without the need for hardware removal.

The hardware-related complications have an incidence between 2.7% and 5%, may develop over the long term, and include lead fractures, lead migration, and hardware erosion.³⁷ Lead migration and fracture may be prevented by placing the junction of the distal end of the DBS electrode wire and the proximal end of the extension wire (the connector) under the scalp and not in the cervical area where excessive motility of the head on the neck can tug and torque the leads and the connector, resulting in fractures. Wire fracture can usually be diagnosed with the use of x-rays. Hardware erosion may be prevented by utilizing low-profile hardware.

Complications related to stimulation are frequently reported, are usually transient, and may include paresthesias; manifestations of capsular stimulation include muscular contractions, dysphasias, and conjugate and disconjugate eye movements. These complications are linked to the target, surrounding structures, stimulation amplitude, and relative location of the electrode within the structure. For example, electrodes placed near the lateral border of the STN may stimulate the nearby internal capsule, leading to contralateral contractions. Emotional lability including acute onset of depression, euphoria, and bouts of laughter have been reported. Accurate location of the DBS electrodes and intraoperative macrostimulation to detect side effects is essential to reduce the incidence of these side effects and avoid the need for revision surgeries.

Specific Disorders: Indications and Efficacy

Movement Disorders

Parkinson’s Disease

The spectrum of movement disorders treated with DBS includes PD, essential tremor, and dystonia. PD is a progressive neurodegenerative disorder classically described as loss of dopaminergic neurons in the substantia nigra. The cardinal features of PD are resting tremor, bradykinesia, rigidity, and postural instability. Replacement of dopamine via dopamine agonists and L-dopa is the mainstay of medical treatment. Patients over time tend to require escalating doses of dopamine equivalents to achieve therapeutic response, and these dose increases can be associated with motor fluctuations (on/off periods) as well as dyskinesias.^37,⁶⁶^–⁶⁸ The circuitry implicated in the pathogenesis of PD is the direct and indirect dopaminergic pathways that begin with dopamine release in the substantia nigra and have downstream effects on the striatum, globus pallidus, subthalamic nucleus, and thalamocortical projections. The net result is hypokinesis resulting from a paucity of glutamatergic excitation from thalamocortical projections.

DBS can improve symptoms, especially those involving the extremities. In addition, DBS, of the STN in particular, can decrease the need for oral dopaminergic replacement, consequently improving dyskinesias.^65,⁶⁹^–⁷² A recent, randomized study showed that in patients under 75 years old with severe motor complications from advanced PD, STN DBS was more effective than medical management alone.⁷³ GPi stimulation is also effective in alleviating some of the motor symptoms of PD, and although some evidence suggests superiority of STN stimulation, other recent evidence suggests the results may be equivalent.⁶³ In 2010, a multicenter study of 299 patients suggested that the primary motor outcome following GPi or STN DBS was equivalent; however, patients undergoing STN stimulation had worse visuomotor processing scores and depression ratings than those undergoing GPi stimulation. However, there was a trend toward increased ICH in the GPi group, and this has been suggested by other studies, as described previously.^64,⁶⁵

With this in mind, there are several key points in determining if a patient with PD is a candidate for DBS. These determinants can be classified as factors related to ensuring a patient can tolerate surgery and improving the chances that a patient will achieve maximal therapeutic benefit from the procedure. The factors related to patient tolerance are both psychosocial and medical.

Regarding patient selection criteria, patients with classical PD, and not those with atypical parkinsonism, are candidates for DBS. Patients with progressive supranuclear palsy, Lewy body disease, and others do not respond well to and may even worsen after surgery.⁷⁴ A corollary to this is that positive response of symptoms to L-dopa predicts outcome and benefit from stereotactic procedures including DBS, according to most authors,^37,^75,⁷⁶ and this relationship was originally demonstrated in patients undergoing stereotactic pallidotomy.⁷⁷ A 30% improvement of the Unified Parkinson’s Disease Rating Scale (Part III) score is a good indication of L-dopa responsiveness and is used as a cutoff point at our institution. An important exception to this is patients with tremor-predominant PD who still obtain good tremor control with STN DBS in spite of L-dopa unresponsiveness. Furthermore, surgical candidates tend to have one or more of the following features: troublesome dyskinesias and motor fluctuations despite optimal therapy, medication resistance, disabling tremor, freezing or rigidity, dystonia, or bradykinesia.

Surgery is more likely to improve symptoms involving the extremities than it does axial symptoms involving posture, balance, speech, and gait.³⁷

Tremor

Essential tremor is a benign, common movement disorder with an estimated prevalence ranging from 0.4% to 5%.⁷⁸ It is characterized by a 4- to 12-Hz tremor that is generally postural or intention associated and disappears at rest. It is often familial, exacerbated by anxiety, and commonly improved with alcohol intake. Generally, tremor can be managed medically with propranolol, a β-adrenergic blocker, or primidone, an anticonvulsant.⁷⁹ In cases of disabling tremor despite optimal medical management, DBS of the VIM nucleus of the thalamus is a treatment option. Patients with distal, resting, or postural tremors of the upper extremities benefit most from surgery. Patients with intention tremor or tremors of the head, neck, voice, or lower extremities are more difficult to treat.⁸⁰ In general, distal tremors respond better than proximal tremors. Furthermore, patients with axial, head, voice, or neck tremors are more challenging to manage and often require bilateral DBS.³⁷ DBS for upper extremity tremor has excellent success rates, with reported ranges of 70% up to 90% of patients having significant resolution of the tremor.⁷⁹ In a prospective single-blind, randomized trial, DBS of the VIM nucleus of the thalamus was as effective for the suppression of drug-resistant tremor with fewer adverse effects than thalamotomy.⁸¹ Again, DBS results are equivalent to those of lesioning procedures but with inherent reversibility of the side effect profile.

Dystonia

Dystonia represents a heterogeneous group of disorders characterized by sustained muscle contractions leading to twisting or repetitive movements and abnormal postures. Dystonias can be broadly categorized into four groups: primary dystonias, secondary dystonias, dystonia plus syndromes, and those associated with other degenerative neurological disorders (heredodegenerative dystonia).

Primary dystonias are syndromes in which no clear etiological factor is responsible for its onset, and the dystonia is the only clinical sign. These patients have normal brain imaging, no history of brain injury, and normal cerebrospinal fluid and other laboratory results. A subset of these patients have a mutation denoted DYT-1, which encodes the TorsinA gene. TorsinA is a member of the AAA family of adenosine triphosphatases (ATPases) and related to the CLP protease/heat shock protein family. It has been localized to the 9q34 locus and is expressed prominently in the substantia nigra pars compacta.⁸² It is the most common mutation leading to childhood-onset primary dystonia, and although other mutations have been identified, they remain rare.⁸³

Secondary dystonias represent a large, heterogeneous group of disorders in which the cause of the dystonia is secondary to other insults including drugs, stroke, tumors, trauma, perinatal anoxic injury, and infections. Dystonia plus syndromes are neurochemical, nondegenerative disorders associated with another movement disorder. These include dopa-responsive dystonia (Segawa syndrome), rapid onset dystonia-parkinsonism, and myoclonus dystonia syndrome. Finally, dystonias may be a part of a neurodegenerative disorder. These disorders include autosomal dominant disorders such as Huntington’s disease, autosomal recessive disorders such as Wilson’s disease and pantothenate kinase–associated neurodegeneration (PKAN), and other metabolic disorders including mitochondrial diseases and the X-linked recessive disorder Lesch-Nyhan syndrome.⁸³

In addition, dysonias can be classified according to the distribution of affected body parts. Generalized dystonia, as the name implies, affects most body parts. Focal dystonia affects a single region of the body, as is the case in blepharospasm (eyes), writer’s cramp, laryngeal or spasmodic dystonia, cranial dystonia (Meige syndrome), and cervical dystonia or torticollis. In segmental dystonia, two or more adjacent body parts are affected, such as in cranial-cervical dystonia, crural dystonia, or brachial dystonia.

The pharmacological therapies available for dystonia are somewhat limited; therefore, surgical alternatives have been developed that include both peripheral procedures including intrathecal baclofen pumps, botulinum toxin injections, and denervation procedures as well as central procedures including thalamotomy and DBS. Historically, thalamotomy was the surgical treatment of choice for dystonia; however, results are variable and DBS, as mentioned before, provides a reversible, controlled therapy relative to ablative procedures.⁸³

Bilateral DBS of the GPi is the surgical treatment of choice for generalized dystonia, of both DYT-1 and non-DYT-1 subtypes.^37,⁸³ Improvements in the 40% to 80% range of motor and disability scores of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMRS) have been reported.⁸⁴^–⁹⁰ In 2005, the French Stimulation du Pallidum Interne dans la Dystonie (SPIDY) Study Group published a study of 22 patients undergoing bilateral GPi DBS for primary, generalized dystonia. The BFMRS movement subscore improved from a mean 46.3 before surgery to 21.0 at 12 months. The disability subscore improved from 11.6 before surgery to 6.5 at 12 months. Similar results have been described in segmental dystonia as well.^83,^85,⁹⁰^–⁹³ A 2006 study from the Deep Brain Stimulation for Dystonia Study Group evaluated 40 patients with primary generalized or segmental dystonia undergoing GPi DBS, and these patients had an average 15.8-point improvement in the movement subscore of the BFMRS.

In generalized dystonias, predictors of good outcome include age of onset older than 5 years and lack of multiple orthopedic deformities.⁹⁴ Additionally, appendicular symptoms tend to be more responsive than axial symptoms.⁹⁵ Regarding focal dystonias, bilateral and unilateral GPi DBS has also shown some efficacy in the management of cervical dystonia, with improvements on the Toronto Western Spasmodic Rating Scale (TWSTRS) ranging from 40% to 60%.^88,⁹⁵^–⁹⁷

Clinical results in secondary dystonia are more disappointing. Tardive dystonia, however, is the exception to this rule, and these patients do derive benefit from DBS.⁹⁷^–¹⁰⁰ There is also a suggestion of benefit in postanoxic dystonia.⁸³ Finally, data are sparse, but DBS may have some role in the palliation of dystonia in neurodegenerative disorders including Lesch-Nyhan syndrome, PKAN, Hallervorden-Spatz disease, and Huntington’s disease.¹⁰¹^–¹⁰⁶

Epilepsy

Despite advances in the medical management of epilepsy, a significant portion of patients remain refractory to maximal therapy. It is estimated that approximately 40% of newly diagnosed epilepsies are pharmacotherapy resistant. That is, approximately 47% of patients become seizure-free (no seizures for 1 year) after initiating a single antiepileptic drug (AED), and only an additional 13% become seizure-free after use of an additional agent.¹⁰⁷ This leaves approximately 40% of patients that may benefit from surgical evaluation. Traditionally, surgical management of epilepsy has centered on lesional or seizure focus resection, but in difficult-to-manage cases, neuromodulation therapies are finding a promising role. These therapies include cerebellar cortex stimulation, vagal nerve stimulation, and DBS of targets including the anterior nucleus (AN) of the thalamus, centromedian (CM) thalamus, STN, and hippocampus.

There is evidence that thalamocortical interactions are important in the development and propagation in various types of seizures.¹⁰⁸^–¹¹² Furthermore, the dorsomedian (DM) nucleus of the thalamus has been shown to be important in the propagation and maintenance of seizures, particularly in limbic epilepsy.^113,¹¹⁴ The AN, as part of the Papez circuit and limbic system, has afferent connections from the hippocampus and mammillary bodies via the mammillothalamic tract and has efferent projections to the cingulate cortex and parahippocampal cortex, which in turn connect widely to the neocortex.^115,¹¹⁶ Bilateral DBS of the AN recently was studied as a therapy for refractory epilepsy in the SANTE (stimulation of the anterior nucleus of the thalamus for epilepsy) trial.¹¹⁷ In this multicenter, double-blind, sham-controlled, randomized trial of 110 patients, subjects receiving stimulation experienced a median reduction in seizures of 56% at 2 years. A 50% responder rate was achieved in 54% of patients, and approximately one quarter of patients receiving stimulation were seizure-free. As a cautionary note, significant side effects of depression, confusion, and memory impairment were seen more commonly in the stimulation group.

Another intracranial stimulation paradigm, where electrical stimulation is automatically delivered to seizure foci, may also prove useful in the management of epilepsy. The NeuroPace RNS system is one such closed-loop system in which electrographic recordings from a patient’s brain are continuously monitored, and stimulation is applied to seizure foci when they are detected. The results of a randomized, double-blind, sham-controlled trial of 191 patients indicated a mean reduction in disabling seizures of 29% compared to 14% in the sham group.¹¹⁸

CM thalamic nucleus stimulation has shown some promise in the management of refractory epilepsy as well. Results currently seem most promising in the management of Lennox-Gastaut syndrome, where an 80% seizure reduction was seen.¹¹⁹ Chkhenkeli and colleagues reported a 40% to 80% reduction of seizure frequency with CM stimulation in patients with mesiotemporal epilepsy.¹²⁰ Other groups report mixed results. Fisher and co-workers, in a study with blinded and open trial arms, did not demonstrate a overall reduction in seizure frequency, except in generalized, tonic-clonic seizures, in a trial of CM thalamus stimulation.¹²¹ Complications including lethargy, confusion, and anxiety have been reported,¹²² and the safety profile of CM stimulation in large numbers of patients has yet to be established.¹¹⁶

Hippocampal stimulation seems to be an obvious option, and early results from several groups seem promising in the management of temporal lobe onset epilepsy, especially those without mesiotemporal sclerosis.¹²³^–¹²⁵ Stimulation of the STN is an appealing option because of its widespread use in the management of PD and its connections to the limbic system via the modulation of the substantia nigra, but results in open-label human trials have been mixed.^126,¹²⁷

Neuropsychiatric Disorders

Perhaps the most exciting new frontier of DBS is the management of neuropsychiatric disorders, namely, OCD and MDD. OCD and MDD are increasingly being considered as circuit-based or “network” problems, and therefore, attempts to modulate these networks have been the surgical goal in treatment of refractory cases. Although still in its early stages, DBS for OCD and MDD has made major advances in the past 15 years. Preliminary results suggest that DBS will become a mainstay in the management of treatment-resistant cases of these disorders in the near future.

Obsessive-Compulsive Disorder

OCD is characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that significantly impact the lives of those afflicted. These obsessions and compulsions become time-consuming and impairing, leading patients to go to great lengths to avoid situations that provoke them. These behaviors are not desired or enjoyed by the patients, and are deleterious to social, scholastic, and occupational functioning. The prevalence in Western countries is approximately 2% of the population,¹²⁸ and OCD is initially managed with pharmacotherapy and cognitive behavioral therapy. OCD is managed with selective serotonin reuptake inhibitors (SSRIs) as a first line, then clomipramine, a tricyclic antidepressant (TCA), as a second line, and finally atypical antipsychotics to augment therapy.¹²⁹ Despite good response to pharmacotherapy in many patients, approximately 7% of patients are refractory to treatment.¹³⁰

Although the details of the neurobiological basis of OCD have yet to be fully elucidated, much neuroimaging work has focused on the cortico-striato-thalamo-cortical circuitry. More specifically, some evidence points to dysfunction in the loops involving the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and basal ganglia.¹²⁹ Specifically, the anterior limb of the internal capsule is the most widely used target for stimulation, and this consists of fiber tracts connecting the thalamus, frontal cortex, and basal ganglia.¹³¹ In movement disorder physiology, the cortico-subcortical loop connects the dorsal basal ganglia to the ventrolateral thalamus. However, as described earlier, a parallel loop involving ventral striatopallidal structures to the mediodorsal thalamus is believed to be the key structure that links motor function to motivational and emotional inputs, and this is further suggested by the presence of limbic cortical inputs to the striatum.^62,¹³²^–¹³⁴

Historically, attempts to modulate or disrupt this aberrant circuitry have consisted of lesioning procedures including subcaudate tractotomy, anterior cingulotomy, limbic leucotomy, and anterior capsulotomy (see Fig. 53.3). Geoffrey Knight first introduced the subcaudate tractotomy in the treatment of movement disorders in the early 1960s,¹³⁵ and clinical improvement in about half of patients has been reported.^136,¹³⁷ Ballantine reported on the use of anterior cingulotomy in the 1980s, with improvements in the range of 25% to 50%.^31,¹³⁸ Limbic leucotomy was introduced by Kelly, which was in essence, a combination of anterior cingulotomy and subcaudate tractotomy. At 16 months in a series of 66, he reported significant improvements in 89% of patients.^139,¹⁴⁰ Anterior capsulotomy was introduced by Talairach³² and popularized by Leksell,²² and large series indicate that nearly half of patients achieve at least a 50% reduction of symptoms, with most others having at least a 33% improvement in symptoms as determined on the Yale-Brown obsessive-compulsive scale (YBOCS).¹⁴¹ Adverse effects for these procedures have similar profiles, with lethargy, confusion, transient incontinence, and personality changes being most common.¹²⁹

The advent of DBS provides a reversible, nondestructive method to modulate these circuits. A series of patients undergoing bilateral stimulation of the ALIC was originally described by Nuttin and associates ⁵² in The Lancet in 1999. Six patients received stimulation with quadripolar electrodes, and four patients continued with stimulation for 21 months; three of the four patients achieved significant improvement of symptoms. Three-year follow-up of a multicenter study of eight patients with OCD demonstrated significant improvement in 75% of patients.⁵¹ Hypomania was reported as an adverse event as was relapse of OCD symptoms with battery failure. STN stimulation has been attempted as well, and a 10-month, double-blind, crossover study published in 2008 demonstrated a mean reduction of symptoms of approximately 32% with active stimulation.⁵⁸ Transient psychiatric and motor symptoms as well as one parenchymal brain hemorrhage were reported as adverse events.

Major Depressive Disorder

MDD is a common, debilitating psychiatric disorder with an estimated lifetime prevalence of approximately 9.5%.¹⁴² The primary medical treatment for MDD is SSRI medication, with other second-line antidepressant medications including monoamine oxidase (MAO) inhibitors, TCAs, and dual serotonin and norepinephrine reuptake inhibitors (SNRIs); however, up to a third of patients do not respond to any of these medications.¹⁴³ The current neurocircuitry model of depression is based on neuroimaging studies that demonstrate abnormalities in regional metabolic brain activity that normalizes with successful treatment. Frontal abnormalities are most reproducibly found, including abnormalities in metabolism of the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex, and ventromedial frontal cortex. Anterior and subgenual cortical changes are also seen, in particular, changes in Brodmann areas (BA) 24 and 25.¹⁴⁴

Similar to OCD, limbic leucotomy, anterior capsulotomy, cingulotomy, and subcaudate tractotomy have all been used to treat depression. Results were promising, with initial responder rates of around 67% for the procedures.¹⁴⁵ Again, DBS provides an attractive option due to its nondestructive, reversible nature. Stimulation of the SCC has been described originally by Mayberg and co-workers in six patients,⁵⁵ and then in a larger study of 20 patients out of Toronto.⁵⁴ Approximately two thirds of patients in these studies had improvement of their MDD symptoms, and 35% of patients in the Toronto study have had resolution of symptoms.

Stimulation of the ALIC has also improved depressive symptoms in patients with comorbid OCD, as described by Greenberg and colleagues, who reported that four of the eight patients with comorbid MDD experienced improvements in mood and affect.⁵¹ The ventral striatum and nucleus accumbens target may also prove to be valuable. The nucleus accumbens projects to the limbic brain areas including the SCC, and as we will describe later, there may be farther-reaching, expanding indications with stimulation of this target in the management of addiction and disorders of brain reward circuitry. A recent study of 15 patients with stimulation of the VC/VS by Malone and colleagues demonstrated a 50% responder rate and 20% remission rate.⁶¹

Emerging Indications

Tourette’s Syndrome

The inherent ability of DBS to modulate neurobehavioral circuitry has opened the door for treatment of a number of otherwise intractable disorders. Tourette’s syndrome (TS) is characterized by chronic vocal and motor tics that have their onset typically in early school age and is often comorbid with attention-deficit hyperactivity disorder or OCD. TS is thought to affect 0.7% to 4.2% of individuals, though symptom severity typically lessens in adulthood.¹⁴⁶

Vocal tics include coughing, clearing one’s throat, and coprolalia. Motor tics include blinking, grimacing, snapping, or movements of the face. These movements or gestures tend to resemble coordinated or repetitive fragments of normal behaviors. Tics are exacerbated by stress, fatigue, and boredom and are often present during sleep.¹⁴⁶ Owing to the nature of tics, they can be disabling from a social, occupational, and overall functioning standpoint if they do not abate in adulthood.

It is thought that disruptions in CSPTC circuits mediate the behavioral disturbances in TS.¹⁴⁷^–¹⁴⁹ Neuroimaging studies suggest abnormalities in the metabolism of the ventral striatum in TS.¹⁵⁰ With this in mind, DBS may have efficacy in treatment of TS. Several reports indicate that both thalamic stimulation and stimulation of the GPi are effective in the reduction of tics.¹⁵¹^–¹⁶⁶

Disorders of Consciousness and Cognition

In 2007, Schiff and associates reported on the use of bilateral thalamic DBS in the management of a 38-year-old patient in a minimally conscious state (MCS).¹⁶⁷ This patient had a severe traumatic brain injury (TBI) leading to inability to communicate or follow commands consistently over 6 years following his injury; however, MRI demonstrated preservation of bihemispheric language networks, but thalamic and midbrain injury. Bilateral DBS was targeted to the anterior interlaminar thalamic nuclei and paralaminar regions of the association nuclei, as these regions had maximal concentrations of calbindin-positive neurons that have projections to supragranular cortical regions and are believed to play a role in arousal. The patient had significant improvements in arousal, limb control, and oral feeding in the DBS on versus off state. Some results in larger trials have been mixed, however. For example, circa 1990, Medtronic initiated a trial for implantation of DBS into vegetative state (VS) patients. These patients received bilateral CM thalamus or cervical spinal cord dorsal columns in patients in a VS. Although some centers reported significant functional improvement,^168,¹⁶⁹ this result was not consistently identified.^168,^170,¹⁷¹ Some of the reasons for the mixed results may be that the group of patients enrolled were heterogeneous in terms of their injuries; that is, patients with widespread cortical or subcortical damage may have less potential for recovery than patients with intact networks and central arousal deficits.¹⁷² Clearly, careful patient selection and further trials must be done to determine the role in patients with TBI and disorders of consciousness.

DBS may find a role in the near future in the management of dementias. The group of Lozano reported on a patient who, during stimulation of the hypothalamus for obesity, began having autobiographical memories.¹⁷³ This finding led to a phase 1 trial evaluating forniceal/hypothalamic DBS in the treatment of Alzheimer’s disease. The study suggested the potential slowing of cognitive decline in their cohort,¹⁷⁴ opening the door to more research in this realm.

Addiction and Eating Disorders

Dysfunction in the reward circuitry underlying eating disorders and addiction is quickly becoming a target for DBS. Over 30 years ago, Quaade and co-workers stereotactically electrocoagulated portions of the lateral hypothalamus and safely achieved some weight reduction in three patients.¹⁷⁵ Furthermore, animal studies have identified the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), and NAc as potential targets for managing obesity.¹⁷⁶ The NAc has overlaps in circuitry with the lateral hypothalamus and may be involved in food reward circuitry. Furthermore, the central role of the NAc in reward circuitry makes it an attractive target in treating addiction. Rat studies suggest that DBS of the NAc may ameliorate cocaine addiction.¹⁷⁷ Preliminary studies in humans undergoing DBS of the NAc for other disorders (including Tourette’s syndrome and OCD) indicate that smoking cessation may be more feasible with NAc stimulation.¹⁷⁸ A group from the Netherlands recently reported NAc stimulation in a single patient leading to both smoking cessation and weight loss.¹⁷⁹ DBS of the bilateral NAc was also reported to reduce alcohol dependency in a patient undergoing the procedure for an anxiety disorder.¹⁸⁰ On the flip side, DBS of the NAc/ventral striatum or subgenual cingulate cortex may show promise in the management of anorexia nervosa.^181,¹⁸² With regard to eating disorders, some early results suggest DBS may be effective in the management of anorexia nervosa.^181,¹⁸²

Conclusion (Table 53.3)

DBS has transformed the management of more than 80,000 advanced and medication refractory patients with movement disorders. DBS is now being explored for the emerging indications in the management of neurobehavioral and neuropsychiatric disorders,¹⁸³^–¹⁸⁵ epilepsy, obesity, Alzheimer’s disease, anorexia, traumatic brain injury, and disorders of consciousness. These emerging indications are enhanced by the intrinsic advantages of reversibility and adjustability of DBS, compared to stereotactic lesioning procedures. Efforts at expanding the clinical utility of DBS must, however, be tempered by ethical considerations and the need for rigorous scientific and evidence-based evaluations of these interventions.

TABLE 53.3 Evidence-Based Medicine Summary of Clinical Results for Deep Brain Stimulation (DBS) Surgery

Evidence Class	Findings
1	DBS of the STN and GPi is effective in the management of the motor symptoms of PD.^63,^65,⁷³ Bilateral GPi stimulation is effective in the treatment of primary generalized or segmental dystonia.^84,⁸⁵ DBS of the VIM nucleus of the thalamus is effective for the suppression of drug-resistant tremor with fewer adverse effects than with thalamotomy.⁸¹ Bilateral DBS of the AN of the thalamus reduces seizure frequency in medically resistant epilepsy.¹¹⁷
2	DBS of the ALIC, VC/VS, NAc ameliorates the symptoms of OCD.^50,^51,^184,¹⁸⁵ DBS of the STN treats the symptoms of OCD.⁵⁸ DBS of the subgenual cingulate gyrus can reduce the symptoms of treatment-resistant depression.^54,⁵⁵ DBS of the VC/VS can be effective in the management of treatment-resistant depression.⁶¹
3	DBS of the bilateral thalamus reduces motor and sonic tics in treatment-refractory Tourette’s syndrome.^158,¹⁶²

ALIC, anterior limb of the internal capsule; AN, anterior nucleus; GPi, globus pallidus interna; MCP, midcommissural point; NAc, nucleus accumbens; OCD, obsessive-compulsive disorder; PD, Parkinson’s disease; STN, subthalamic nucleus; VC/VS, ventral capsule/ventral striatum; VIM, ventralis intermedius.

Selected Key References

Deuschl G., Schade-Brittinger C., Krack P., et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355(9):896-908.

Follett K.A., Weaver F.M., Stern M., et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2010;362:2077-2091.

Greenberg B.D., Gabriels L.A., Malone D.A.Jr., et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2008.

Kopell B.H., Greenberg B.D. Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry. Neurosci Biobehav Rev. 2008;32(3):408-422.

Lozano A.M., Mayberg H.S., Giacobbe P., et al. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2008;64(6):461-467.

Rezai A.R., Machado A.G., Deogaonkar M., et al. Surgery for movement disorders. Neurosurgery. 2008;62(Suppl 2):809-838. discussion 809-838

Schuurman P.R., Bosch D.A., Bossuyt P.M., et al. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. 2000;342:461-468.

Vidailhet M., Vercueil L., Houeto J.L., et al. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med. 2005;352:459-467.

Please go to expertconsult.com to view the complete list of references.

References

1. Medtronic. Parkinson’s Disease Treatment with Medtronic DBS Therapy. Accessed at http://www.medtronic.com/your-health/parkinsons-disease/therapy/ October 6, 2010