Deep Brain Stimulation

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Philip A. Starr, Robert S. Turner, Geoff Rau, Nadja Lindsey, Susan Heath, Monica Volz, Jill L. Ostrem and William J. Marks Jr.

Object

Deep brain stimulation (DBS) of the globus pallidus internus (GPI) is a promising new procedure for the treatment of dystonia. The authors describe their technical approach for placing electrodes into the GPI in awake patients with dystonia, including methodology for electrophysiological mapping of the GPI in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit.

Methods

Twenty-three adult and pediatric patients with various forms of dystonia were included in this study. Baseline neurological status and DBS-related improvement in motor function were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The implantation of DBS leads was performed using magnetic resonance (MR) imaging–based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol.

Conclusions

Physiologically guided implantation of DBS electrodes in patients with dystonia was technically feasible in the awake state in most patients, and the morbidity rate was low. Spontaneous discharge rates of GPI neurons in dystonia were similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than rates. Active electrode locations associated with robust improvement (> 70% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance from the pallidocapsular border of 3.6 mm.

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Frank Hertel, Mark Züchner, Christian Decker, Edward Erken, Stefani Libri, Marion Schmitt and Martin Bettag

✓ The authors describe a 58-year-old man with sudden onset of a unilateral tremor caused by a midbrain lesion that affected the substantia nigra and the cerebellothalamic pathway. There were also clinical and neuroimaging signs of a communicating chronic hydrocephalus. The patient was severely handicapped by this tremor, which was a typical Holmes tremor with rest, posture, and intention components. Parkinson disease or multiple-system atrophy as causes for the tremor could be ruled out by DaTSCAN and 123I iodobenzamide and single-photon emission computerized tomography (SPECT), respectively.

The tremor was completely supressed by temporary and permanent cerebrospinal fluid release after ventriculoperitoneal shunt placement, without any additional medication, for a period of 6 months. Afterward, the tremor returned, and the patient had to be treated by a stereotactic electrode implantation in the contralateral ventralis intermedius nucleus, which led to complete tremor suppression during the 1.5-year follow-up period.

In this case report, the authors present the clinical description and the electrophysiological, SPECT, and magnetic resonance imaging data of a rare combination of symptoms and their surgical treatment.

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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

Object

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.

Methods

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.

Conclusions

Analysis of these results suggests that a shorter MER-determined STN length alone does not reliably predict the incidence of stimulation-induced side effects.

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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

Object

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.

Methods

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.

Conclusions

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.

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Zelma H. T. Kiss, Kristina Doig, Michael Eliasziw, Ranjiit Ranawaya and Oksana Suchowersky

Object

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.

Methods

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.

Conclusions

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.

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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.

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Hiroki Toda, Clement Hamani and Andres Lozano

Deep brain stimulation (DBS) has become a mainstay of treatment for patients with movement disorders. This modality is directed at modulating pathological activity within basal ganglia output structures by stimulating some of their nuclei, such as the subthalamic nucleus (STN) and the globus pallidus internus (GPi), without making permanent lesions. With the accumulation of experience, indications for the use of DBS have become clearer and the effectiveness and limitations of this form of therapy in different clinical conditions have been better appreciated. In this review the authors discuss the efficacy of DBS in the treatment of dystonia and levodopa-induced dyskinesias. The use of DBS of the STN and GPi is very effective for the treatment of movement disorders induced by levodopa. The relative benefits of using the GPi as opposed to the STN as a target are still being investigated. Bilateral GPi stimulation is gaining importance in the therapeutic armamentarium for the treatment of dystonia. The DYT1 forms of generalized dystonia and cervical dystonias respond to DBS better than secondary dystonia does. Discrimination between the diverse forms of dystonia and a better understanding of the pathophysiological features of this condition will serve as a platform for improved outcomes.

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Ron L. Alterman, Jay L. Shils, Mark Gudesblatt and Michele Tagliati

The authors demonstrate that high-frequency electrical stimulation dorsal to the subthalamic nucleus (STN) can directly suppress levodopa-induced dyskinesias. This 63-year-old woman with idiopathic Parkinson disease underwent surgery for placement of bilateral subthalamic deep brain stimulation (DBS) electrodes to control progressive rigidity, motor fluctuations, and levodopa-induced dyskinesias. The model 3389 DBS leads were implanted with microelectrode guidance. Magnetic resonance imaging confirmed proper placement of the leads. Postoperatively the patient exhibited improvement in all of her parkinsonian symptoms; however, her right leg dyskinesias had not improved. Based on their previous experiences treating levodopa-induced dyskinesias with subthalamic stimulation through the more dorsally located contacts of the model 3387 lead, the authors withdrew the implanted 3389 lead 3 mm. Following relocation of the lead they were able to suppress the right leg dyskinesias by using the most dorsal contacts. The patient's dopaminergic medication intake increased slightly. These findings indicate that electrical stimulation dorsal to the STN can directly suppress levodopa-induced dyskinesias independent of dopaminergic medication changes. The 3389 lead may provide inadequate coverage of the subthalamic region for some patients.

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Guido Nikkhah, Thomas Prokop, Bernhard Hellwig, Carl Hermann Lücking and Christoph B. Ostertag

✓ Holmes tremor is caused by structural lesions in the perirubral area of the midbrain. Patients often present with associated symptoms such as dystonia and paresis, which are usually refractory to medical therapy. Here, the authors describe two patients in whom both tremor and associated dystonia improved markedly following unilateral stimulation of the thalamic nucleus ventralis intermedius.

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Dipankar Nandi, Simon Parkin, Richard Scott, Jonathan L. Winter, Carole Joint, Ralph Gregory, John Stein and Tipu Z. Aziz

✓ The authors report the neurological, neurophysiological, and neuropsychological effects of using long-term bilateral pallidal high-frequency deep brain stimulation (DBS) in a case of disabling camptocormia. Deep brain stimulation electrodes were implanted stereotactically to target the globus pallidus internus (GPi) bilaterally. Local field potentials (FPs) were recorded using the DBS electrodes and concurrent abdominal flexor electromyography (EMG) potentials during camptocormic episodes. Videotaped assessments of the movement disorder and neuropsychological evaluations of the patient before implantation and 6 months after initiation of pallidal stimulation were recorded.

There was significant functional improvement following long-term pallidal stimulation, and some improvement was noted in neuropsychological scores. A temporal correlation between the GPi FPs and EMG-recorded rectus abdominis potentials was evident. There were no treatment-related adverse effects. The authors have found that long-term pallidal stimulation was safe and offered functional benefit to a patient with this severely disabling condition. The physiological studies may help further the understanding of the pathophysiology of this rare entity.