An estimated 20% of patients with major depression are refractory to existing therapies. The purpose of this review is to provide a theoretical and neuroscientific framework in which to interpret new work in the field of surgical treatment for depression. This review focuses on existing clinical and imaging data, current disease models, and results of recent case reports and patient series that together may inform the construction of appropriate clinical trials for the surgical treatment of refractory depression.
Deep Brain Stimulation
Aviva Abosch and G. Rees Cosgrove
Joshua J. Wind and Douglas E. Anderson
The history of psychosurgery is described and analyzed. This historical perspective largely begins with analysis of the work of Egas Moniz in the development of the leukotomy, and follows the rise and fall of its popularity in the 1900s. The reemergence of psychosurgical procedures and the development of new therapeutic technologies such as vagus nerve stimulation and deep brain stimulation are discussed. In addition, an introduction to the field of neuroethics is provided, given its importance in any discussion about surgical therapy for psychiatric patients.
Bianca M. L. Stelten, Lieke H. M. Noblesse, Linda Ackermans, Yasin Temel, and Veerle Visser-Vandewalle
Addiction or substance dependence is a psychiatric disorder that affects many individuals in the general population. Different theories concerning the neurobiological aspects of addiction have been proposed. Special attention has been paid to models concerning dysregulation of the reward circuit and the inhibitory control system within the cortico-basal ganglia-thalamocortical pathways. In the past, attempts have been made to treat patients suffering from addiction by performing psychosurgery. Lesions were created in specific brain regions that were believed to be dysfunctional in addiction. Procedures such as cingulotomy, hypothalamotomy, and resection of the substantia innominata and the nucleus accumbens have been described as a treatment for severe addictive disorders. Deep brain stimulation, a neurosurgical treatment that has been proven to be a safe alternative for lesions in the treatment of movement disorders, has more recently been proposed as treatments for severe psychiatric conditions such as treatment-refractory obsessive-compulsive disorder and depression. With the expanding knowledge of the neurobiology of addiction, deep brain stimulation could be a future option in the treatment arsenal of addiction.
Jason S. Hauptman, Antonio A. F. DeSalles, Randall Espinoza, Mark Sedrak, and Warren Ishida
The goal of this study was to evaluate the definition of treatment-resistant depression (TRD), review the literature regarding deep brain stimulation (DBS) for TRD, and identify potential anatomical and functional targets for future widespread clinical application.
A comprehensive literature review was performed to determine the current status of DBS for TRD, with an emphasis on the scientific support for various implantation sites.
The definition of TRD is presented, as is its management scheme. The rationale behind using DBS for depression is reviewed. Five potential targets have been identified in the literature: ventral striatum/nucleus accumbens, subgenual cingulate cortex (area 25), inferior thalamic peduncle, rostral cingulate cortex (area 24a), and lateral habenula. Deep brain stimulation electrodes thus far have been implanted and activated in only the first 3 of these structures in humans. These targets have proven to be safe and effective, albeit in a small number of cases.
Surgical intervention for TRD in the form of DBS is emerging as a viable treatment alternative to existing modalities. Although the studies reported thus far have small sample sizes, the results appear to be promising. Various surgical targets, such as the subgenual cingulate cortex, inferior thalamic peduncle, and nucleus accumbens, have been shown to be safe and to lead to beneficial effects with various stimulation parameters. Further studies with larger patient groups are required to adequately assess the safety and efficacy of these targets, as well as the optimal stimulation parameters and long-term effects.
Dirk Rasche, Patricia C. Rinaldi, Ronald F. Young, and Volker M. Tronnier
Electrical intracerebral stimulation (also referred to as deep brain stimulation [DBS]) is a tool for the treatment of chronic pain states that do not respond to less invasive or conservative treatment options. Careful patient selection, accurate target localization, and identification with intraoperative neurophysiological techniques and blinded test evaluation are the key requirements for success and good long-term results. The authors present their experience with DBS for the treatment of various chronic pain syndromes.
In this study 56 patients with different forms of neuropathic and mixed nociceptive/neuropathic pain syndromes were treated with DBS according to a rigorous protocol. The postoperative follow-up duration ranged from 1 to 8 years, with a mean of 3.5 years. Electrodes were implanted in the somatosensory thalamus and the periventricular gray region. Before implantation of the stimulation device, a double-blinded evaluation was carefully performed to test the effect of each electrode on its own as well as combined stimulation with different parameter settings.
The best long-term results were attained in patients with chronic low-back and leg pain, for example, in so-called failed–back surgery syndrome. Patients with neuropathic pain of peripheral origin (such as complex regional pain syndrome Type II) also responded well to DBS. Disappointing results were documented in patients with central pain syndromes, such as pain due to spinal cord injury and poststroke pain. Possible reasons for the therapeutic failures are discussed; these include central reorganization and neuroplastic changes of the pain-transmitting pathways and pain modulation centers after brain and spinal cord lesions.
The authors found that, in carefully selected patients with chronic pain syndromes, DBS can be helpful and can add to the quality of life.
Patrick B. Senatus, David Teeple, Shearwood McClelland III, Seth L. Pullman, Qiping Yu, Blair Ford, Guy M. McKhann II, and Robert R. Goodman
Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target.
Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas.
In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior–posterior difference was 0.53 ± 0.65 mm, whereas the medial–lateral direction differed by 0.25 ± 0.43 mm. The ventral boundary of the STN defined by MER was 2 ± 0.72 mm below the calculated target (all values are the means ± standard deviation). All patients attained clinical improvement, similar to previous reports.
In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.
Shearwood McClelland III, Brian Kim, Linda M. Winfield, Blair Ford, Tresha A. Edwards, Seth L. Pullman, Qiping Yu, Guy M. McKhann II, and Robert R. Goodman
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a popular treatment for patients with medically refractory Parkinson disease. Many surgeons believe that microelectrode recording (MER) during DBS electrode implantation is needed to optimize placement, whereas stimulation-induced side effects such as paresthesias, dystonic contractions, dyskinesias, and ocular motor signs that become apparent postoperatively may be an indicator of the proximity of the electrode to various boundaries of the STN. This study was performed to evaluate the relationship between mapping of the STN by using MER and postoperative stimulation-induced side effects.
Eighty-two electrodes implanted in 75 patients between March 1999 and March 2003 were retrospectively examined to evaluate the length of the STN defined by MER, and the number of and threshold for postoperative stimulation-induced side effects. Electrodes were typically tested with increasing stimulation amplitudes (maximum 6 V) by using a monopolar array.
The 82 electrodes were associated with 97 stimulation-induced side effects. The mean time between surgery and testing stimulation-induced side effects was 3.9 months. Statistical analysis (two-tailed t-test) revealed no significant difference in the number of stimulation-induced side effects (or the mean threshold for paresthesias, the most common side effect) for electrodes associated with an STN length less than 4.5 mm (13 electrodes) compared with those associated with an STN greater than or equal to 4.5 mm (69 electrodes, p = 0.616). For every electrode, the target adjustment based on MER results was within 2 mm of the image-planned target (usually 1 mm anterior). In the x axis (medial–lateral orientation), there was no systematic difference in adjustments made for the electrodes associated with the shorter compared with the longer STN lengths. In the y axis (anterior–posterior orientation), there was a very small statistically significant difference in the mean adjustment (0.4 mm) between the two groups.
Analysis of these results suggests that a shorter MER-determined STN length alone does not reliably predict the incidence of stimulation-induced side effects.
Shearwood McClelland III, Blair Ford, Patrick B. Senatus, Linda M. Winfield, Yunling E. Du, Seth L. Pullman, Qiping Yu, Steven J. Frucht, Guy M. McKhann II, and Robert R. Goodman
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues.
The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits.
The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were “on” and “off” medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging–determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location.
The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.
Zelma H. T. Kiss, Kristina Doig, Michael Eliasziw, Ranjiit Ranawaya, and Oksana Suchowersky
Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is beneficial for generalized dystonia and has been proposed as a treatment for cervical dystonia. The Canadian Stereotactic/Functional and Movement Disorders Groups designed a pilot project to investigate the following hypothesis: that bilateral DBS of the GPi will reduce the severity of cervical dystonia at 1 year of follow up, as scored in a blinded fashion by two neurologists using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Secondary outcome measures included pain and disability subscores of the TWSTRS, Short Form–36 quality of life index, and the Beck Depression Inventory.
Three patients have undergone surgery in Calgary with a followup duration of 7.4 ± 5.9 months (mean ± standard deviation). One patient underwent inadvertent ineffective stimulation for the first 3 months and did not experience a benefit until DBS programming was corrected. All three patients had rapid response to stimulation, with the muscles relaxing immediately and abnormal movements improving within days. Total TWSTRS scores improved by 79%, and severity subscores improved significantly, from 15.7 ± 2.1 to 7.7 ± 2.9 (paired ttest, p = 0.02). Pain and disability subscores improved from 25.5 ± 4.1 to 3.3 ± 3.1 (paired ttest, p = 0.002) and from 13.3 ± 4.9 to 3.3 ± 4.2 (paired ttest, p = 0.06), respectively.
Although it is too early to reach broad conclusions, this report of preliminary results confirms the efficacy of DBS of the GPi for cervical dystonia.
Erwin B. Montgomery Jr.
Deep brain stimulation (DBS) has a record of safety and efficacy for an expanding range of indications. Recently, the Food and Drug Administration provided approval through a Humanitarian Device Exemption for DBS of the globus pallidus internus and subthalamic nucleus for the treatment of dystonia. There is increasing clinical experience demonstrating that DBS is also effective for other hyperkinetic disorders such as chorea from a variety of causes. The selection criteria, intraoperative targeting, and the postoperative management of DBS for hyperkinetic disorders are discussed.