Deep Brain Stimulation

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Robert J. Maciunas, Brian N. Maddux, David E. Riley, Christina M. Whitney, Mike R. Schoenberg, Paula J. Ogrocki, Jeffrey M. Albert and Deborah J. Gould

Object

The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS.

Methods

Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted.

Results

In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures.

Conclusions

Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

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Chikashi Fukaya, Yoichi Katayama, Toshikazu Kano, Takafumi Nagaoka, Kazutaka Kobayashi, Hideki Oshima and Takamitsu Yamamoto

Object

Writer's cramp is a type of idiopathic focal hand dystonia characterized by muscle cramps that accompany execution of the writing task specifically. In this report, the authors describe the clinical outcome after thalamic deep brain stimulation (DBS) therapy in patients with writer's cramp and present an illustrative case with which they compare the effects of pallidal and thalamic stimulation. In addition to these results for the clinical effectiveness, they also examine the best point and pattern for therapeutic stimulation of the motor thalamus, including the nucleus ventrooralis (VO) and the ventralis intermedius nucleus (VIM), for writer's cramp.

Methods

The authors applied thalamic DBS in five patients with writer's cramp. The inclusion criteria for the DBS trial in this disorder were a diagnosis of idiopathic writer's cramp and the absence of a positive response to medication. The exclusion criteria included significant cognitive dysfunction, active psychiatric symptoms, and evidence of other central nervous system diseases or other medical disorders. In one of the cases, DBS leads were implanted into both the globus pallidus internus and the VO/VIM, and test stimulation was performed for 1 week. The authors thus had an opportunity to compare the effects of pallidal and thalamic stimulation in this patient.

Results

Immediately after the initiation of thalamic stimulation, the neurological deficits associated with writer's cramp were improved in all five cases. Postoperatively all preoperative scale scores indicating the seriousness of the writer's cramp were significantly lower (p < 0.001). In the patient in whom two DBS leads were implanted, the clinical effect of thalamic stimulation was better than that of pallidal stimulation. During the thalamic stimulation, the maximum effect was obtained when stimulation was applied to both the VO and the VIM widely, compared with being applied only within the VO.

Conclusions

The authors successfully treated patients with writer's cramp by thalamic DBS. Insofar as they are aware, this is the first series in which writer's cramp has been treated with DBS. Thalamic stimulation appears to be a safe and valuable therapeutic option for writer's cramp.

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Sepehr Sani, Kirk Jobe, Adam Smith, Jeffrey H. Kordower and Roy A. E. Bakay

Object

Given the success of deep brain stimulation (DBS) in a variety of applications (for example, Parkinson disease and essential tremor), other indications for which there is currently little effective therapy are being evaluated for clinical use of DBS. Obesity may be one such indication. Studies of the control of feeding and appetite by neurosurgical lesioning have been completed previously. This study was conducted to test the authors' hypothesis that continuous bilateral stimulatory inhibition of the rat lateral hypothalamic nucleus (LH) would lead to significant and sustained decrease in food intake and subsequent weight loss.

Methods

Sixteen Sprague–Dawley rats were maintained on a high-fat diet. Daily food intake and weight gain were measured for 7 days, at which time the animals underwent stereotactic placement of 0.25-mm-diameter bipolar stimulating electrodes bilaterally in the LH. On postoperative Day 7, eight animals began to receive continuous stimulation of the LH. The remaining eight animals were left unstimulated as the control group. Individual animal weight, food intake, and water intake were monitored daily and continuously throughout the experiment until postoperative Day 24.

Results

There was a decreased rate of weight gain after surgery in all animals, but the unstimulated group recovered and resumed a linear weight gain curve. The stimulated group, however, failed to show weight gain and remained below the mean baseline for body mass. There was a significant weight loss between the stimulated and unstimulated groups. On postoperative Day 24, compared with the day of surgery (Day 0), the unstimulated group had a mean weight gain of 13.8%, whereas the stimulated group had a 2.3% weight loss on average (p = 0.001), yielding a 16.1% weight difference between the two groups.

Conclusions

Bilateral electrical stimulatory inhibition of the LH is effective in causing significant and sustained weight loss in rats.

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Mayumi Kitagawa, Jun-Ichi Murata, Haruo Uesugi, Ritsuko Hanajima, Yoshikazu Ugawa and Hisatoshi Saito

Object

The aim of the present study is to evaluate the topographical distribution of somatosensory evoked potentials (SSEPs) in the subthalamic area, including the zona incerta (ZI). Determination of this distribution may help in the correct placement of deep brain stimulation (DBS) leads.

Methods

Intraoperative SSEPs were recorded from contacts of DBS electrodes at 221 sites in 41 patients: three patients with essential tremor and 38 with Parkinson disease who underwent implantation of DBS electrodes for the relief of severe tremor or parkinsonism.

Results

Two distinct SSEPs were recorded in the subthalamic area. One was a monophasic positive wave with a mean latency of 15.8 ± 0.9 msec, which the authors designated subthalamic P16. Using both cephalic and noncephalic references, subthalamic P16 was only recorded in the ventral part of the ZI (mean 6.6 ± 1. 3 mm posterior to the midcommissure point, 4.8 ± 1.2 mm inferior to the anterior commissure–posterior commissure line, and 9.7 ± 0.6 mm lateral to the midline). When bipolar recordings were made, the traces showed a phase reversal at the caudal part of the ZI. The second potential is a positive–negative SSEP recorded throughout the entire subthalamic area. The mean latencies of the initial positive peak and the major negative peak were 13.6 ± 1.1 msec and 16.4 ± 1.1 msec, respectively. Several small notches were superimposed on the peaks, and their amplitudes were largest at the contact close to the medial lemniscus.

Conclusions

The results indicate that intraoperative SSEPs from DBS electrodes are helpful in refining stereotactic targets in the thalamus and subthalamic areas.

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Donald C. Shields, Alessandra Gorgulho, Eric Behnke, Dennis Malkasian and Antonio A. F. Desalles

Object

Deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease is often very effective for treatment of debilitating motor symptoms. Nevertheless, the small size of the STN and its proximity to axonal projections results in multiple side effects during high-frequency stimulation. Contralateral eye deviation is produced in a small percentage of patients, but the precise mechanism of this side effect is at present poorly understood.

Methods

Contralateral eye deviation was produced by high-frequency stimulation of 22 contact sites in nine patients undergoing deep brain stimulation of the STN. The precise locations of these contacts were calculated and compiled in order to locate the stimulated structure responsible for eye deviation.

Results

The mean x, y, and z coordinates associated with contralateral eye deviation were found to be 11.57, 2.03, and 3.83 mm lateral, posterior, and inferior to the anterior commissure–posterior commissure midpoint, respectively. The point described by these coordinates is located within the lateral anterosuperior border of the STN.

Conclusions

Given that stimulation of frontal eye field cortical regions produces similar contralateral conjugate eye deviation, these results are best explained by electrical current spread to nearby frontal eye field axons coursing lateral to the STN within the internal capsule. Thus, placement of the implanted electrode in a more medial, posterior, and inferior position may bring resolution of these symptoms by reducing the amount of current spread to internal capsule axons.

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John Spooner, Hong Yu, Chris Kao, Karl Sillay and Peter Konrad

✓The authors present a case in which high-frequency electrical stimulation of the cingulum using standard deep brain stimulation (DBS) technology resulted in pain relief similar to that achieved with cingulotomy and superior to that achieved with periventricular gray matter (PVG) stimulation.

This patient had a complete spinal cord injury at the C-4 level and suffered from medically refractory neuropathic pain. He underwent placement of bilateral cingulum and unilateral PVG DBS electrodes and a 1-week blinded stimulation trial prior to permanent implantation of a pulse generator. During the stimulation trial, the patient's pain level was assessed using a visual analog scale, and pain medication usage was recorded. During this period the patient was blinded to stimulation parameters. Stimulation of the cingulum provided better pain control than PVG stimulation or medication alone.

The authors believe that cingulum stimulation can benefit patients with severe neuropathic pain that is refractory to other treatments. Advantages over cingulotomy include reversibility and the ability to adjust stimulation parameters for optimum efficacy.

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Galit Kleiner-Fisman, Grace S. Lin Liang, Paul J. Moberg, Anthony C. Ruocco, Howard I. Hurtig, Gordon H. Baltuch, Jurg L. Jaggi and Matthew B. Stern

Object

Medically refractory dystonia has recently been treated using deep brain stimulation (DBS) targeting the globus pallidus internus (GPI). Outcomes have varied depending on the features of the dystonia. There has been limited literature regarding outcomes for refractory dystonia following DBS of the subthalamic nucleus (STN).

Methods

Four patients with medically refractory, predominantly cervical dystonia underwent STN DBS. Intraoperative assessments with the patients in a state of general anesthesia were performed to determine the extent of fixed deformities that might predict outcome. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) preoperatively and 3 and 12 months following surgery by a rater blinded to the study. Mean changes and standard errors of the mean in scores were calculated for each subscore of the two scales. Scores were also analyzed using analysis of variance and probability values were generated. Neuropsychological assessments and quality of life ratings using the 36-Item Short Form Health Survey (SF-36) were evaluated longitudinally.

Results

Significant improvements were seen in motor (p = 0.04), disability (p = 0.02), and total TWSTRS scores (p = 0.03). Better outcomes were seen in those patients who did not have fixed deformities. There was marked improvement in the mental component score of the SF-36. Neuropsychological function was not definitively impacted as a result of the surgery.

Conclusions

Deep brain stimulation of the STN is a novel target for dystonia and may be an alternative to GPI DBS. Further studies need to be performed to confirm these conclusions and to determine optimal candidates and stimulation parameters.

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Philip A. Starr, Nicholas M. Barbaro, Neil H. Raskin and Jill L. Ostrem

Object

Cluster headache (CH) is the most severe of the primary headache disorders. Based on the finding that regional cerebral blood flow is increased in the ipsilateral posterior hypothalamic region during a CH attack, a novel neurosurgical procedure for CH was recently introduced: hypothalamic deep brain stimulation (DBS). Two small case series have been described. Here, the authors report their technical approach, intraoperative physiological observations, and 1-year outcomes after hypothalamic DBS in four patients with medically intractable CHs.

Methods

Patients underwent unilateral magnetic resonance (MR) imaging–guided stereotactic implantation of a Medtronic DBS (model 3387) lead and Soletra pulse generator system. Intended tip coordinates were 3 mm posterior, 5 mm inferior, and 2 mm lateral to the midcommissural point. Microelectrode recording and intraoperative test stimulation were performed. Lead locations were measured on postoperative MR images. The intensity, frequency, and severity of headaches throughout a 1-week period were tracked in patient diaries immediately prior to surgery and after 1 year of continuous stimulation.

At the 1-year follow-up examination, DBS had produced a greater than 50% reduction in headache intensity or frequency in two of four cases. Active contacts were located 3 to 6 mm posterior to the mammillothalamic tract. Neurons in the target region showed low-frequency tonic discharge.

Conclusions

In two previously published case series, headache relief was obtained in many but not all patients. The results of these open-label studies justify a larger, prospective trial but do not yet justify widespread clinical application of this technique.

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Christopher Kenney, Richard Simpson, Christine Hunter, William Ondo, Michael Almaguer, Anthony Davidson and Joseph Jankovic

Object

The object of this study was to assess the long-term safety of deep brain stimulation (DBS) in a large population of patients with a variety of movement disorders.

Methods

All patients treated with DBS at the authors' center between 1995 and 2005 were assessed for intraoperative, perioperative, and long-term adverse events (AEs).

A total of 319 patients underwent DBS device implantation. Of these 319, 182 suffered from medically refractory Parkinson disease; the other patients had essential tremor (112 patients), dystonia (19 patients), and other hyperkinetic movement disorders (six patients). Intraoperative AEs were rare and included vasovagal response in eight patients (2.5%), syncope in four (1.2%), severe cough in three (0.9%), transient ischemic attack in one (0.3%), arrhythmia in one (0.3%), and confusion in one (0.3%). Perioperative AEs included headache in 48 patients (15.0%), confusion in 16 (5.0%), and hallucinations in nine (2.8%). Serious intraoperative/perioperative AEs included isolated seizure in four patients (1.2%), intracerebral hemorrhage in two patients (0.6%), intraventricular hemorrhage in two patients (0.6%), and a large subdural hematoma in one patient (0.3%). Persistent long-term complications of DBS surgery included dysarthria (4.0%), worsening gait (3.8%), cognitive dysfunction (4.0%), and infection (4.4%). Revisions were completed in 25 patients (7.8%) for the following reasons: loss of effect, lack of efficacy, infection, lead fracture, and lead migration. Hardware-related complications included 12 lead fractuxres and 10 lead migrations.

Conclusions

The authors conclude that in their 10-year experience, DBS has proven to be safe for the treatment of medically refractory movement disorders.

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Jerzy L. Slowinski, John D. Putzke, Ryan J. Uitti, John A. Lucas, Margaret F. Turk, Bruce A. Kall and Robert E. Wharen

Object

The object of this study was to assess the results of unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for management of advanced Parkinson disease (PD).

Methods

A clinical series of 24 patients (mean age 71 years, range 56–80 years) with medically intractable PD, who were undergoing unilateral magnetic resonance imaging–targeted, electrophysiologically guided STN DBS, completed a battery of qualitative and quantitative outcome measures preoperatively (baseline) and postoperatively, using a modified Core Assessment Program for Intracerebral Transplantations protocol.

The mean follow-up period was 9 months. Statistically significant improvement was observed in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score (18%), the total UPDRS PART III score (31%), the contralateral UPDRS Part III score (63%), and scores for axial motor features (19%), contralateral tremor (88%), rigidity (60%), bradykinesia (54%), and dyskinesia (69%), as well as the Parkinson's Disease Quality of Life questionnaire score (15%) in the on-stimulation state compared with baseline. Ipsilateral symptoms improved by approximately 15% or less. Performance on the Purdue pegboard test improved in the contralateral hand in the on-stimulation state compared with the off-stimulation state (38%, p < 0.05). The daily levodopa-equivalent dose was reduced by 21% (p = 0.018). Neuropsychological tests revealed an improvement in mental flexibility and a trend toward reduced letter fluency. There were no permanent surgical complications. Of the 16 participants with symmetrical disease, five required implantation of the DBS unit on the second side.

Conclusions

Unilateral STN DBS is an effective and safe treatment for selected patients with advanced PD. Unilateral STN DBS provides improvement of contralateral motor symptoms of PD as well as quality of life, reduces requirements for medication, and possibly enhances mental flexibility. This method of surgical treatment may be associated with a reduced risk and may provide an alternative to bilateral STN DBS for PD, especially in older patients or patients with asymmetry of parkinsonism.