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PubMed2004

Deep brain stimulation.

During the last decade deep brain stimulation (DBS) has become a routine method for the treatment of advanced Parkinson's disease (PD), leading to striking improvements in motor function and quality of life of PD patients. It is associated with minimal morbidity. The rationale of targeting specific structures within basal ganglia such as the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) is strongly supported by the current knowledge of the basal ganglia pathophysiology, which is derived from extensive experimental work and which provides the theoretical basis for surgical therapy in PD. In particular, the STN has advanced to the worldwide most used target for DBS in the treatment of PD, due to the marked improvement of all cardinal symptoms of the disease. Moreover on-period dyskinesias are reduced in parallel with a marked reduction of the equivalent daily levodopa dose following STN-DBS. The success of the therapy largely depends on the selection of the appropriate candidate patients and on the precise implantation of the stimulation electrode, which necessitates careful imaging-based pre-targeting and extensive electrophysiological exploration of the target area. Despite the clinical success of the therapy, the fundamental mechanisms of high-frequency stimulation are still not fully elucidated. There is a large amount of evidence from experimental and clinical data that stimulation frequency represents a key factor with respect to clinical effect of DBS. Interestingly, high-frequency stimulation mimics the functional effects of ablation in various brain structures. The main hypotheses for the mechanism of high-frequency stimulation are: (1) depolarization blocking of neuronal transmission through inactivation of voltage dependent ion-channels, (2) jamming of information by imposing an efferent stimulation-driven high-frequency pattern, (3) synaptic inhibition by stimulation of inhibitory afferents to the target nucleus, (4) synaptic failure by stimulation-induced neurotransmitter depletion. As the hyperactivity of the STN is considered a functional hallmark of PD and as there is experimental evidence for STN-mediated glutamatergic excitotoxicity on neurons of the substantia nigra pars compacta (SNc), STN-DBS might reduce glutamatergic drive, leading to neuroprotection. Further studies will be needed to elucidate if STN-DBS indeed provides a slow-down of disease progression.

Deep Brain Stimulation↗

PubMed2005

Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) has been reported to relieve motor symptoms and levodopa-induced dyskinesia in patients with advanced Parkinson disease (PD). Although it has been suggested that stimulation of the STN may be superior to stimulation of the GPi, comparative trials are limited. OBJECTIVE: To extend our randomized, blinded pilot comparison of the safety and efficacy of STN and GPi stimulation in patients with advanced PD. DESIGN: This study represents the combined results from our previously published, randomized, blinded, parallel-group pilot study and additional patients enrolled in our single-center extension study. SETTING: Oregon Health and Science University in Portland.Patients Twenty-three patients with idiopathic PD, levodopa-induced dyskinesia, and response fluctuations were randomized to implantation of bilateral GPi or STN stimulators. Patients and evaluating clinicians were blinded to stimulation site. All patients were tested preoperatively while taking and not taking medications and after 3, 6, and 12 months of DBS. MAIN OUTCOME MEASURES: Postoperatively, response of symptoms to DBS, medication, and combined medication and DBS was evaluated. Twenty patients (10 in the GPi group and 10 in the STN group) completed 12-month follow-up. RESULTS: Off-medication Unified Parkinson's Disease Rating Scale motor scores were improved after 12 months of both GPi and STN stimulation (39% vs 48%). Bradykinesia tended to improve more with STN than GPi stimulation. No improvement in on-medication function was observed in either group. Levodopa dose was reduced by 38% in STN stimulation patients compared with 3% in GPi stimulation patients (P = .08). Dyskinesia was reduced by stimulation at both GPi and STN (89% vs 62%). Cognitive and behavioral complications were observed only in combination with STN stimulation. CONCLUSION: Stimulation of either the GPi or STN improves many features of advanced PD. It is premature to exclude GPi as an appropriate target for DBS in patients with advanced disease.

Activities of Daily Living↗

PubMed2006

Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation.

BACKGROUND: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor functions in those with Parkinson disease but may worsen frontal functions such as verbal fluency (VF). In contrast, low-frequency DBS leads to deterioration of motor functions. It is not known whether low-frequency STN DBS also has an effect on frontal functions. OBJECTIVE: To examine whether low-frequency STN DBS in contrast to high-frequency STN DBS has a positive effect on frontal functions on the basis of VF test results. DESIGN: A double-blind randomized crossover experiment to compare performance in 4 VF subtests and motor performance at 10 Hz, 130 Hz, and no stimulation. SETTING: University hospitals in Düsseldorf and Cologne, Germany. PATIENTS: Twelve patients with Parkinson disease 3 months or more after bilateral electrode implantation into the STN. MAIN OUTCOME MEASURE: Mean number of words in VF at different stimulation frequencies. RESULTS: The VF was significantly better at 10 Hz (48.3 words) compared with 130 Hz and showed a nonsignificant trend toward worsening at 130 Hz (42.3 words) compared with no stimulation (43.8 words). These results were consistent across all subtests. CONCLUSIONS: The study provides evidence of a beneficial effect of low-frequency (10 Hz) STN DBS on VF, which may be caused by activating neural pathways projecting to the frontal cortex. In addition, the study reproduces the negative effect of therapeutic high-frequency STN DBS on VF. The study results provide evidence for a frequency-dependent modulation of cognitive circuits involving the STN.

Aged↗

PubMed2007

Neuropsychological performance following staged bilateral pallidal or subthalamic nucleus deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) has the potential to significantly reduce motor symptoms in advanced Parkinson's disease (PD). Controversy remains about non-motor effects of DBS and the relative advantages of treatment at two brain targets, the globus pallidus internus (GPi) and the subthalamic nucleus (STN). We investigated effects of DBS on neuropsychological functioning in 42 patients with advanced PD randomly assigned to receive staged bilateral DBS surgery of either the GPi or STN. Patients underwent neuropsychological assessment prior to and 6 months after unilateral surgery. Twenty-nine subsequently underwent surgery to the contralateral side and completed a second follow-up neuropsychological evaluation 15 months later. Unilateral treatment resulted in small but statistically significant reductions in performance on several measures, including verbal fluency and working memory. A similar pattern was observed after bilateral treatment. Reductions in verbal associative fluency were significant only after left-sided treatment. There were few significant differences related to treatment at the two surgical targets. Supplementary analyses suggested that decrements in select neuropsychological domains following DBS are unrelated to age or post-surgical reduction in dopaminergic medication dose. Findings are discussed with reference to possible causes of neuropsychological decline and the need for further controlled studies of specific neuropsychological effects of DBS.

Aged↗

PubMed2006

Globus pallidus deep brain stimulation in dystonia.

Globus pallidus deep brain stimulation (GPi-DBS) is a useful alternative in the treatment of dystonia. Patients selected for GPi-DBS were prospectively rated with the Unified Dystonia Rating Scale (UDRS). Also, "blinded" videotape assessments were performed. Eleven patients were identified. Compared with pre-DBS scores, there were improvements in mean total UDRS score (15.3%) and in the following subscores: neck (18.18%), trunk (32.9%), arm (17.9%), and leg (19.9%). One patient developed a skin infection and erosion requiring surgical debridement. GPi-DBS is a safe and effective treatment for generalized dystonia in patients who remained impaired, despite optimal medical therapy.

Adolescent↗

PubMed2003

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Animals↗

PubMed2001

Simultaneous thalamic deep brain stimulation and implantable cardioverter-defibrillator.

Thalamic deep brain stimulation is becoming increasingly popular for the control of drug-refractory tremor. Implantable cardiac pacemakers and defibrillators are commonly used therapeutic modalities. Concerns exist about the potential interactions between these 2 devices in the same patient, but no experience has been reported previously. We describe a patient with essential tremor who had a deep brain stimulator implanted into the left ventral intermediate nucleus of thalamus, who subsequently needed an implantable cardioverter-defibrillator. Despite concerns about possible interactions between the 2 types of implanted electrical devices (i.e., a situation similar to drug-drug interactions), the deep brain stimulator and the implanted pacemaker-defibrillator functioned appropriately, and no interaction occurred in our patient.

Aged↗

PubMed2005

Double electrodes simultaneous stimulation and implantation technique in deep brain stimulation.

Posttraumatic tremor is often one of the causes of disability in head injury patients. Usually, pharmacotherapy for this type of tremor is not effective. Since early 1970s, surgical ablation of the ventral thalamus has been used to treat various types of tremor. Nowadays, deep brain stimulation (DBS) confirms its efficacy in alleviating different forms of tremor, including posttraumatic tremor. Such therapy has been reported achieving around 80% success rate in the treatment of posttraumatic tremor. These successful results suggest that the application of DBS therapy can be considered as one of the alternative treatments for minimizing the tremor occurring from different pathologies.

Adult↗

PubMed2001

Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats.

Deep brain stimulation of the subthalamic nucleus is an established therapeutic strategy for patients with Parkinson's disease. Although the exact mechanisms of action remain unknown, it is noteworthy that dopaminergic medication can be markedly reduced after neurostimulation of the subthalamic nucleus. Previously, we have shown that deep brain stimulation of the subthalamic nucleus is followed by an increase of striatal extracellular dopamine metabolites in naive rats. In the present study we examined the effects of deep brain stimulation on striatal monoamine metabolism in the intrastriatal 6-hydroxydopamine rat model of Parkinson's disease. Deep brain stimulation of the subthalamic nucleus was followed by a delayed increase of extracellular 3,4-dihydroxyphenylacetic and homovanillic whereas dopamine levels were unchanged in stimulated rats and controls. Our results indicate that deep brain stimulation of the subthalamic nucleus affects significantly striatal dopaminergic metabolism in 6-hydroxydopamine lesioned rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2005

Sources and effects of electrode impedance during deep brain stimulation.

OBJECTIVE: Clinical impedance measurements for deep brain stimulation (DBS) electrodes in human patients are normally in the range 500-1500 Omega. DBS devices utilize voltage-controlled stimulation; therefore, the current delivered to the tissue is inversely proportional to the impedance. The goals of this study were to evaluate the effects of various electrical properties of the tissue medium and electrode-tissue interface on the impedance and to determine the impact of clinically relevant impedance variability on the volume of tissue activated (VTA) during DBS. METHODS: Axisymmetric finite-element models (FEM) of the DBS system were constructed with explicit representation of encapsulation layers around the electrode and implanted pulse generator. Impedance was calculated by dividing the stimulation voltage by the integrated current density along the active electrode contact. The models utilized a Fourier FEM solver that accounted for the capacitive components of the electrode-tissue interface during voltage-controlled stimulation. The resulting time- and space-dependent voltage waveforms generated in the tissue medium were superimposed onto cable model axons to calculate the VTA. RESULTS: The primary determinants of electrode impedance were the thickness and conductivity of the encapsulation layer around the electrode contact and the conductivity of the bulk tissue medium. The difference in the VTA between our low (790 Omega) and high (1244 Omega) impedance models with typical DBS settings (-3 V, 90 mus, 130 Hz pulse train) was 121 mm3, representing a 52% volume reduction. CONCLUSIONS: Electrode impedance has a substantial effect on the VTA and accurate representation of electrode impedance should be an explicit component of computational models of voltage-controlled DBS. SIGNIFICANCE: Impedance is often used to identify broken leads (for values > 2000 Omega) or short circuits in the hardware (for values < 50 Omega); however, clinical impedance values also represent an important parameter in defining the spread of stimulation during DBS.

Brain↗

PubMed2002

Introduction to the programming of deep brain stimulators.

The clinical success of deep brain stimulation (DBS) for treating Parkinson's disease, tremor, or dystonia critically depends on the quality of postoperative neurologic management. Movement disorder specialists becoming involved with this therapy need to acquire new skills to optimally adapt stimulation parameters and medication after implantation of a DBS system. In clinical practice, the infinite number of possible parameter settings in DBS can be reduced to few relevant combinations. In this article, the authors describe a general scheme of selecting stimulation parameters in DBS and provide clinical and neurophysiological arguments for such a standardized algorithm. They also describe noninvasive technical trouble shooting by using programming features of the commercially available neurostimulation devices.

Dystonia↗

PubMed2003

Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.

Aged↗

PubMed2001

Deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) is making a major impact in patients with advanced Parkinson's disease who continue to be disabled despite the best available medical therapy. Stimulation of the internal segment of the globus pallidus (GPi) or the subthalamic nucleus (STN) can improve tremor, rigidity, bradykinesia and gait disturbances in Parkinson's disease and improve the day-to-day activities of patients with these disabling symptoms. While the mechanism of action of DBS remains poorly understood, the success of technique in the treatment of movement disorders is bringing into question traditional concepts of the organization and of the basal ganglia and spearheading a re-examination of the nature and function of brain areas involved in the control of movement. Future developments in this rapidly advancing area will include the elucidation of the mechanism of action of DBS and technical advances in surgical techniques, in electrode design and in choosing better stimulation parameters. These advances will improve the scope and effectiveness of DBS and expand its clinical indications.

Journal Article↗

PubMed2004

Stabilization clamp for insertion of deep brain stimulation electrodes: technical note.

BACKGROUND: Deep brain stimulation (DBS) electrodes are being implanted with increasing frequency for the management of movement disorders and chronic pain. Success with this neuro-augmentative technique requires accurate electrode lead placement. In order to enhance accuracy of final lead placement and ease of insertion, we describe a useful and reliable DBS electrode lead stabilization device developed and used at our centre. MATERIALS AND METHODS: The DBS electrode stabilization device consists of a 2-clamp system designed to fit the Leksell stereotactic frame. The clamps work in series to secure the stereotactic lead at the time of its final positioning in the desired subcortical target without the need of fluoroscopic control. RESULTS: The DBS electrode stabilization device has been used in 30 patients for 54 electrode implantations at our institution since 2000. Postoperative magnetic resonance imaging was performed in all cases and confirmed accurate placement of the electrodes. CONCLUSIONS: Accurate electrode lead placement is critical for the clinical efficacy of DBS systems. The simple and reliable stabilization device described here is easy to operate and enhances the final placement accuracy of DBS electrode leads.

Brain↗

PubMed1998

Deep brain stimulation for movement disorders.

Chronic deep brain stimulation (DBS) is a promising technique for the treatment of movement disorders. Thalamic stimulation is now an established surgical procedure for parkinsonian and essential tremor. Pallidal and subthalamic stimulation are under active investigation as treatments for Parkinson's disease. Although high-frequency DBS at these sites has similar behavioral effects as lesioning, the physiologic mechanisms underlying the beneficial effect of DBS is not well understood and may be extremely complex. DBS offers a potential advantage over ablative therapy because stimulation-induced complications are reversible, and the stimulation parameters are adjustable to minimize complications and maximize therapeutic effects. With this added safety, bilateral stimulation or use of a stimulator following a prior procedure may be preferable to bilateral ablative procedures.

Electric Stimulation Therapy↗

PubMed2006

Criteria for deep-brain stimulation in Parkinson's disease: review and analysis.

Deep-brain stimulation is currently the most effective surgical treatment for advanced Parkinson's disease. The relevant targets to date are the subthalamic nucleus and the globus pallidus internus, although the thalamus (ventralis intermedius nucleus) is preferred in tremor-dominant, aged Parkinson's disease patients. Long-term benefit in cardinal parkinsonian signs, motor fluctuations and dyskinesia has been reported in 5-year follow-up studies of subthalamic nucleus deep-brain stimulation. However, some psychiatric consequences have raised important issues and emphasized the need for an experienced deep-brain stimulation surgical team. This team should be multidisciplinary and involve movement disorder neurologists, neurosurgeons, neuropsychologists and psychiatrists. The recent observation that deep-brain stimulation of the pedunculopontine nucleus improves axial signs, possibly even in those less responsive to levodopa, brings new hope to the management of advanced Parkinson's disease.

Deep Brain Stimulation↗

PubMed2004

Comparison of pallidal and subthalamic deep brain stimulation for the treatment of levodopa-induced dyskinesias.

Deep brain stimulation (DBS) can relieve dyskinesias effectively and safely. This modality is applied most commonly in the treatment of dyskinesias associated with levodopa therapy for Parkinson disease. The subthalamic nucleus (STN) and globus pallidus internus (GPi) are the most common surgical targets. Deep brain stimulation of the GP has a direct antidyskinetic effect, whereas relief of dyskinesias by DBS of the STN depends on postoperative reduction of dopaminergic medications. Outcomes are similar for DBS in these two sites despite the different mechanisms by which the stimulation relieves dyskinesias. Deep brain stimulation of the STN has become the surgical treatment of choice in many movement disorders programs but this modality has not been compared with DBS of the GPi in randomized controlled trials, and the superiority of one site over the other remains unproven. In the absence of data demonstrating superiority, selection of the stimulation target should be individualized to meet the needs of each patient. Selection of the target should be based on the patient's most disabling symptoms, response to medications (including side effects), and the goals of therapy, with consideration given to the different antidyskinetic effects of DBS of the STN and GPi.

Antiparkinson Agents↗

PubMed2005

Frameless stereotaxy using bone fiducial markers for deep brain stimulation.

OBJECT: Functional neurosurgical interventions such as deep brain stimulation (DBS) are traditionally performed with the aid of a stereotactic frame. Although frameless techniques have been perceived as less accurate, data from a recent phantom study of a modified frameless approach demonstrated a laboratory accuracy exceeding that obtained using a common frame system. The present study was conducted to evaluate the accuracy of a frameless system in routine clinical use. METHODS: Deep brain stimulation leads were implanted in 38 patients by using a skull-mounted trajectory guide and an image-guided workstation. Registration was accomplished with bone fiducial markers. Final lead positions were measured on postoperative computerized tomography scans and compared with the planned lead positions. The accuracy of the Leksell frame within the clinical situation has been reported on in a recent study; these raw data served as a comparison data set. The difference between expected and actual lead locations in the x plane was 1.4 mm in the frame-based procedure and 1.6 mm in the frameless procedure. Similarly, the difference in the y plane was 1.6 mm in the frame-based system and 1.3 mm in the frameless one. The error was greatest in the z plane, that is, 1.7 mm in the frame-based method and 2 mm in the frameless system. Multivariate analysis of variance demonstrated no statistically significant difference in the accuracy of the two methods. CONCLUSIONS: The accuracy of the frame-based and frameless systems was not statistically significantly different (p = 0.22). Note, however, that frameless techniques offer advantages in patient comfort, separation of imaging from surgery, and decreased operating time.

Deep Brain Stimulation↗