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Deep brain stimulation of the subcallosal cingulate gyrus for depression: anatomical location of active contacts in clinical responders and a suggested guideline for targeting

Clinical article

Clement Hamani, Helen Mayberg, Brian Snyder, Peter Giacobbe, Sidney Kennedy, and Andres M. Lozano

Object

Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG), including Brodmann area 25, is currently being investigated for the treatment of major depressive disorder (MDD). As a potential emerging therapy, optimal target selection within the SCG has still to be determined. The authors compared the location of the electrode contacts in responders and nonresponders to DBS of the SCG and correlated the results with clinical outcome to help in identifying the optimal target within the region. Based on the location of the active contacts used for long-term stimulation in responders, the authors suggest a standardized method of targeting the SCG in patients with MDD.

Methods

Postoperative MR imaging studies of 20 patients with MDD treated with DBS of the SCG were analyzed. The authors assessed the location of the active contacts relative to the midcommissural point and in relation to anatomical landmarks within the medial aspect of the frontal lobe. For this, a grid with 2 main lines was designed, with 1 line in the anterior-posterior and 1 line in the dorsal-ventral axis. Each of these lines was divided into 100 units, and data were converted into percentages. The anterior-posterior line extended from the anterior commissure (AC) to the projection of the anterior aspect of the corpus callosum (CCa). The dorsal-ventral line extended from the inferior portion of the CC (CCi) to the most ventral aspect of the frontal lobe (abbreviated “Fr” for the formula).

Results

Because the surgical technique did not vary across patients, differences in stereotactic coordinates between responders and nonresponders did not exceed 1.5 mm in any axis (x, y, or z). In patients who responded to the procedure, contacts used for long-term stimulation were in close approximation within the SCG. In the anterior-posterior line, these contacts were located within a 73.2 ± 7.7 percentile distance from the AC (with the AC center being 0% and the line crossing the CCa being 100%). In the dorsal-ventral line, active contacts in responders were located within a 26.2 ± 13.8 percentile distance from the CCi (with the CCi edge being 0% and the Fr inferior limit being 100%). In the medial-lateral plane, most electrode tips were in the transition between the gray and white matter of SCG.

Conclusions

Active contacts in patients who responded to DBS were relatively clustered within the SCG. Because of the anatomical variability in the size and shape of the SCG, the authors developed a method to standardize the targeting of this region.

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Editorial: Magnetic resonance imaging and deep brain stimulation

Tejas Sankar and Andres M. Lozano

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Histological analysis of the location of effective thalamic stimulation for tremor

Case report

Robert E. Gross, Edward G. Jones, Jonathan O. Dostrovsky, Catherine Bergeron, Anthony E. Lang, and Andres M. Lozano

✓ Chronic electrical stimulation of the thalamus is an effective treatment for essential and parkinsonian tremor. Although the preferred surgical target is generally accepted to lie within the ventral intermediate nucleus (Vim), the relationship between the surgically defined target and the true histologically defined target is addressed in only a few reports, due in large measure to the need for advanced cytoarchitectonic techniques to define the borders of the thalamic nuclei. The authors report on a patient who underwent effective thalamic deep brain stimulation (DBS) for tremor. By defining the boundaries of the thalamic nuclei, they were able to relate effective DBS to electrode location within the anterior region of the ventral posterior lateral nucleus—the proprioceptive shell of the sensory nucleus—and the posteroventral region of the ventral lateral nucleus, which are equivalent to the Vim defined by Hassler, et al.

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Editorial: Presentation to publication

Travis S. Tierney and Andres M. Lozano

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Long-term follow up of bilateral deep brain stimulation of the subthalamic nucleus in patients with advanced Parkinson disease

Galit Kleiner-Fisman, David N. Fisman, Elspeth Sime, Jean A. Saint-Cyr, Andres M. Lozano, and Anthony E. Lang

Object. The use of deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with a marked initial improvement in individuals with advanced Parkinson disease (PD). Few data are available on the long-term outcomes of this procedure, however, or whether the initial benefits are sustained over time. The authors present the long-term results of a cohort of 25 individuals who underwent bilateral DBS of the STN between 1996 and 2001 and were followed up for 1 year or longer after implantation of the stimulator.

Methods. Patients were evaluated at baseline and repeatedly after surgery by using the Unified Parkinson's Disease Rating Scale (UPDRS); the scale was applied to patients during periods in which antiparkinsonian medications were effective and periods when their effects had worn off. Postoperative UPDRS total scores and subscores, dyskinesia scores, and drug dosages were compared with baseline values, and changes in the patients' postoperative scores were evaluated to assess the possibility that the effect of DBS diminished over time.

In this cohort the median duration of follow-up review was 24 months (range 12–52 months). The combined (ADL and motor) total UPDRS score during the medication-off period improved after 1 year, decreasing by 42% relative to baseline (95% confidence interval [CI 35–50%], p < 0.001) and the motor score decreased by 48% (95% CI 42–55%, p < 0.001). These gains did diminish over time, although a sustained clinical benefit remained at the time of the last evaluation (41% improvement over baseline, 95% CI 31–50%; p < 0.001). Axial subscores at the time of the last evaluation showed only a trend toward improvement (p = 0.08), in contrast to scores for total tremor (p < 0.001), rigidity (p < 0.001), and bradykinesia (p = 0.003), for which highly significant differences from baseline were still present at the time of the last evaluation. Medication requirements diminished substantially, with total medication doses reduced by 38% (95% CI 27–48%, p < 0.001) at 1 year and 36% (95% CI 25–48%, p < 0.001) at the time of the last evaluation; this decrease may have accounted, at least in part, for the significant decrease of 46.4% (95% CI 20.2–72.5%, p = 0.007) in dyskinesia scores obtained by patients during the medication-on period. No preoperative demographic variable, such as the patient's age at the time of disease onset, age at surgery, sex, duration of disease before surgery, preoperative drug dosage, or preoperative severity of dyskinesia, was predictive of long-term outcome. The only predictor of a better outcome was the patient's preoperative response to levodopa.

Conclusions. In this group of patients with advanced PD who underwent bilateral DBS of the STN, sustained improvement in motor function was present a mean of 2 years after the procedure, and sustained reductions in drug requirements were also achieved. Improvements in tremor, rigidity, and bradykinesia were more marked and better sustained over time than improvements in axial symptoms. A good preoperative response to levodopa predicted a good response to surgery.

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Editorial: Deep brain stimulation in children

Ron Levy and Andres M. Lozano

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Tremor cells in the human thalamus: differences among neurological disorders

Jason A. Brodkey, Ronald R. Tasker, Clement Hamani, Mary Pat McAndrews, Jonathan O. Dostrovsky, and Andres M. Lozano

Object. Thalamic neurons firing at frequencies synchronous with tremor are thought to play a critical role in the generation and maintenance of tremor. The authors studied the incidence and locations of neurons with tremor-related activity (TRA) in the thalamus of patients with varied pathological conditions—including Parkinson disease (PD), essential tremor (ET), multiple sclerosis (MS), and cerebellar disorders—to determine whether known differences in the effectiveness of thalamic stereotactic procedures for these tremors could be correlated to differences in the incidence or locations of TRA cells.

Methods. Seventy-five operations were performed in 61 patients during which 686 TRA cells were recorded from 440 microelectrode trajectories in the thalamus. The locations of the TRA cells in relation to electrophysiologically defined thalamic nuclei and the commissural coordinates were compared among patient groups.

The authors found that TRA cells are present in patients with each of these disorders and that these cells populate several nuclei in the ventral lateral tier of the thalamus. There were no large differences in the locations of TRA cells among the different diagnostic classes, although there was a difference in the incidence of TRA cells in patients with PD, who had greater than 3.8 times more cells per thalamic trajectory than patients with ET and approximately five times more cells than patients with MS or cerebellar disorders.

Conclusions. There was an increased incidence of TRA in the thalamus of patients with PD. The location of thalamic TRA cells in patients with basal ganglia and other tremor disorders was similar.

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Psychiatric symptoms in patients with Parkinson disease presenting for deep brain stimulation surgery

Valerie Voon, Jean Saint-Cyr, Andres M. Lozano, Elena Moro, Yu Yan Poon, and Anthony E. Lang

Object. Postoperative psychiatric symptoms have been associated with subthalamic deep brain stimulation (DBS) for Parkinson disease (PD), and preoperative psychiatric vulnerability, the effects of surgery, stimulation, medication changes, and psychosocial adjustment have been proposed as causative factors. The variables involved in whether preoperative psychiatric symptoms improve or worsen following surgery are not yet known. In the present study, preoperative psychiatric symptoms were systematically assessed in patients with PD presenting for routine preoperative psychiatric assessment.

Methods. Forty consecutive patients with PD presenting for DBS were interviewed using the Mini International Neuropsychiatric Inventory. Current depressive symptoms were quantified using clinician- and patient-rated depression scales. Seventy-eight percent of patients had at least one lifetime or current Axis I psychiatric diagnosis. The prevalence of depression was 60% (95% confidence interval [CI] 45–85), psychosis 35% (95% CI 25–50), and anxiety 40% (95% CI 25–55). These prevalence rates were comparable to or greater than those in the general population of patients with PD. Twenty-three percent of patients required psychiatric treatment for current symptoms prior to being considered eligible for DBS.

Conclusions. As part of the selection process for surgery, members of the study population were chosen for their lack of overt dementia or other active disabling psychiatric symptomatology. The incidence rates of psychiatric disorders, including those diseases occurring in the general population affected with PD, were greater than expected. Data in the present study lead one to question the reliability of patient-rated depression scales as the sole instrument for assessing depression. The authors highlight the need for evidence-based guidelines in the management of these preoperative symptoms as well as the involvement of psychiatric personnel in the assessment and management of these symptoms.

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Editorial

Deep brain stimulation and depression

Kim J. Burchiel

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Editorial: Obsessive-compulsive disorder

Nir Lipsman and Andres M. Lozano