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The effect of cystic cavities on deep brain stimulation in the basal ganglia: a simulation-based study.

Although the therapeutic effect of deep brain stimulation (DBS) is well recognized, a fundamental understanding of the mechanisms responsible is still not known. In this study finite element method (FEM) modelling and simulation was used in order to study relative changes of the electrical field extension surrounding a monopolar DBS electrode positioned in grey matter. Due to the frequently appearing cystic cavities in the DBS-target globus pallidus internus, a nucleus of grey matter with and without a cerebrospinal fluid filled cystic cavity was modelled. The position, size and shape of the cyst were altered in relation to the electrode. The simulations demonstrated an electrical field around the active element with decreasing values in the radial direction. A stepwise change was present at the edge between grey and white matters. The cyst increased the radial extension and changed the shape of the electrical field substantially. The position, size and shape of the cyst were the main influencing factors. We suggest that cystic cavities in the DBS-target may result in closely related unexpected structures or neural fibre bundles being stimulated and could be one of the reasons for suboptimal clinical effects or stimulation-induced side effects.

Action Potentials↗

Operative and hardware complications of deep brain stimulation for movement disorders.

The objective of this investigation was to present the operative and hardware complications encountered during follow-up of patients with in situ deep brain stimulators. The study took the form of a retrospective chart review on a series of consecutive patients who were treated successfully with insertion of deep brain stimulators at a single centre by a single surgeon between 1999 and 2005. During the study period, a total of 60 patients underwent 96 procedures for implantation of unilateral or bilateral DBS electrodes. The mean follow-up period was 43.7 months (range 6-78 months) from the time of the first procedure. No patients were lost to follow-up or died. Eighteen patients (30%) developed 28 adverse events, requiring 28 electrodes to be replaced. Seven patients developed two adverse events and two patients developed three adverse events. The rate of adverse events per electrode-year was 8%. We observed a higher proportion of early complications (<6 months postoperatively) in patients with Parkinson's disease, while dystonic patients had more late complications (>6 months postoperatively) and no early complications. Thirty per cent of our patients developed an adverse event that could potentially lead to revision of the implanted hardware. In patients with Parkinson's disease most of the complications tend to occur during the first 6 months postoperatively, while in dystonic patients most occur between 12 and 24 months postoperatively.

Adult↗

Are complications less common in deep brain stimulation than in ablative procedures for movement disorders?

The side effects and complications of deep brain stimulation (DBS) and ablative lesions for tremor and Parkinson's disease were recorded in 256 procedures (129 DBS and 127 lesions). Perioperative complications (seizures, haemorrhage, confusion) were rare and did not differ between the two groups. The rate of hardware-related complications was 17.8%. In ventral intermediate (Vim) thalamotomies, the rate of side effects was 74.5%, in unilateral Vim-DBS 47.3%, while in 7 bilateral Vim-DBS 13 side effects occurred. Most of the side effects of Vim-DBS were reversible upon switching off, or altering, stimulation parameters. In unilateral pallidotomy, the frequency of side effects was 21.9%, while in bilateral staged pallidotomies it was 33.3%. Eight side effects occurred in 11 procedures with pallidal DBS. In 22 subthalamic nucleus DBS procedures, 23 side effects occurred, of which 8 were psychiatric or cognitive. Unilateral ablative surgery may not harbour more postoperative complications or side effects than DBS. Some of the side effects following lesioning are transient and most but not all DBS side effects are reversible. In the Vim DBS is safer than lesioning, while in the pallidum, unilateral lesions are well tolerated.

Cerebral Hemorrhage↗

Improvement in a quantitative measure of bradykinesia after microelectrode recording in patients with Parkinson's disease during deep brain stimulation surgery.

It is widely accepted that patients with Parkinson's disease experience immediate but temporary improvement in motor signs after surgical implantation of subthalamic nucleus (STN) deep brain stimulating electrodes before the electrodes are activated, although this has never been formally studied. Based on anecdotal observations that limb mobility improved just after microelectrode recording (MER) during deep brain stimulation (DBS) procedures, we designed a prospective study to measure upper extremity bradykinesia using a quantitative measure of angular velocity. Measurements were made pre- and post-MER and during intraoperative DBS. Analysis of 98 STN DBS procedures performed on 61 patients showed that MER did not create adverse clinical symptoms despite concerns that MER increases morbidity. Quantitative upper extremity bradykinesia improved after MER alone, and further improvement was seen during intraoperative DBS. Electrophysiological data from each case were then compared to the improvement in bradykinesia post-MER alone and a significant correlation was found between the improvement in arm bradykinesia, the number of passes through the STN with somatosensory driving, and also with the number of arm cells with somatosensory driving in the STN, but not with total number of passes, total number of passes through the STN, or total number of cells with somatosensory driving in the STN. This study demonstrates that there is a significant improvement in upper extremity bradykinesia just after MER, before inserting or activating the DBS electrode in patients with Parkinson's disease who undergo STN DBS.

Aged↗

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes.

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.

Adolescent↗

Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years.

The effects of subthalamic nucleus deep brain stimulation were studied in 52 consecutive patients (13 over age 70, 15 under age 60, 24 age 60 to 70). All groups had improvement of motor fluctuations and dyskinesia. Patients over age 70 had worsening of Unified Parkinson's Disease Rating Scale motor scores on medication, despite less medication reduction. Their activities of daily living and axial subscores worsened, particularly in those with preoperative gait difficulties.

Age Factors↗

Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome.

In response to recent publicity regarding the potential use of deep brain stimulation (DBS) for reducing tic severity in Tourette's syndrome (TS), the Tourette Syndrome Association convened a group of TS and DBS experts to develop recommendations to guide the early use and potential clinical trials of DBS for TS and other tic disorders. The goals of these recommendations are to ensure that all surgical candidates are (1) fully informed about the risks, benefits, and alternative treatments available; (2) receive a comprehensive evaluation before surgery to ensure that DBS is clearly the appropriate clinical treatment choice; and (3) that early clinical experience will be documented publicly to facilitate rational decision-making for both clinical care and future clinical trials.

Deep Brain Stimulation↗

The globus pallidus, deep brain stimulation, and Parkinson's disease.

Parkinson's disease (PD) is caused by the degeneration of the dopaminergic neurons in the substantia nigra. Loss of dopaminergic innervation leads to hyperactivity in the internal segment of the globus pallidus (GPi), the main output nucleus of the basal ganglia and to a profound disturbance in the function of motor circuits. Lesions of the GPi (or in its upstream modulator, the subthalamic nucleus) can greatly improve the motor symptoms of PD presumably by reducing this pathological activity. Paradoxically, high-frequency electrical stimulation of the GPi (deep brain stimulation, DBS) mimics the effects of pallidotomy and has become an accepted therapeutic technique. The mechanisms underlying the beneficial effects of pallidal DBS are not known. Various mechanisms that might account for inhibiting or disrupting the pathological pallidal outflow by high-frequency DBS have been proposed ranging from depolarization block to stimulation-evoked release of GABA, and these are discussed.

Animals↗

Chronic bilateral subthalamic deep brain stimulation in a patient with homozygous deletion in the parkin gene.

Chronic subthalamic nucleus deep brain stimulation (STN-DBS) is an efficacious treatment for idiopathic Parkinson's disease (PD) that cannot be further improved by medical therapy. We present a case of an individual with juvenile parkinsonism caused by homozygous deletion of exon 3 in the parkin gene with disabling long-term side-effects from levodopa who underwent bilateral STN neuromodulation. Parkin-linked parkinsonism may show clinical features different from sporadic PD, yet it shares levodopa responsiveness. Because levodopa responsiveness is a predictor of STN-DBS efficacy, we argued that this kind of surgical approach might be efficacious in hereditary parkin-linked juvenile parkinsonism. We evaluated clinical and functional assessment before and 12 months after surgery. The results showed that the Unified Parkinson Disease Rating Scales Motor score improved by 84% in our patient, the levodopa equivalent daily dose medication (LEDD) was reduced by 66%, and, finally, disabling and severe dyskinesias disappeared.

Antiparkinson Agents↗

Thalamic deep brain stimulation: effects on the nontarget limbs.

Unilateral thalamic ventral intermediate (VIM) deep brain stimulation (DBS) is now accepted as an effective treatment for essential tremor (ET) and tremor related to Parkinson's disease (PD). The effects of unilateral placement on the side ipsilateral to the surgical site have not been carefully evaluated. To systematically assess the effects ipsilateral to the surgical side and to determine the effects of device inactivation on the baseline tremor, we evaluated tremor in 73 patients approximately 3 months after their unilateral thalamic placement. Assessment included blinded and unblinded ratings using the Unified Parkinson's Disease Rating Scale for PD patients and a modified Tremor Rating Scale in ET patients. All measures of tremor contralateral to the implantation site improved significantly and robustly in both PD and ET. Implantation did not worsen tremor by any measure on the ipsilateral side. There was mild ipsilateral improvement as measured by lower observed tremor scores in ET (6.0 +/- 1.8 to 5.0 +/- 1.9, P < 0.005), but not PD. There was no rebound augmentation of tremor in either hand after the devices were deactivated in either group. We conclude that VIM DBS may mildly improve ipsilateral ET, and that concerns about meaningful ipsilateral tremor augmentation after device deactivation are not warranted.

Aged↗

Deep brain stimulation of the subthalamic nucleus: selection of patients and clinical results.

Deep brain stimulation of the subthalamic nucleus has been proved to be an effective treatment for advanced Parkinson's disease when therapeutical strategies have failed. A correct selection of candidates for surgery is fundamental to obtain a good clinical effect. In this study we present our protocol of patient selection. In addition we report the data relative to the different causes of exclusion and the clinical efficacy of the electrical stimulation of the subthalamic nucleus at 3 months and 1 year follow-up.

Antiparkinson Agents↗

Thalamic deep brain stimulation for posttraumatic action tremor.

We report a case of thalamic deep brain stimulation (DBS) for treatment of posttraumatic tremor. An 18-year-old right-handed man developed a disabling and medically refractory action tremor in the right upper extremity 9 months after sustaining diffuse axonal injury in a motor vehicle collision. DBS of the left ventral intermediate nucleus of the thalamus (Vim) suppressed the tremor without complication and should be considered as an option for the management of intractable posttraumatic tremor.

Adolescent↗

Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation.

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.

Adult↗

Subthalamic deep brain stimulation does not induce striatal dopamine release in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN) is an increasingly prevalent treatment for advanced Parkinson's disease (PD). Its main mechanism of action is thought to be a reduction in the inhibitory outflow from basal ganglia to cerebral cortex. However, recent animal experiments have led to the suggestion that high frequency stimulation of the STN also acts by promoting dopamine release. We tested this hypothesis by performing [11C]raclopride PET on and off stimulation in six patients with PD and implanted STN stimulators. There was no difference in tracer binding in the striatum between the two testing conditions. We conclude that high frequency stimulation of the STN does not act by increasing dopamine release.

Aged↗

Deep brain stimulation in the management of neuropathic pain and multiple sclerosis tremor.

Deep brain stimulation (DBS) of the central gray matter was an important component of the surgical management of chronic, drug-refractory, central neuropathic pain until only a decade ago. However, in the recent past, this technique has been increasingly neglected and has been largely replaced by motor cortex stimulation (MCS). The results of MCS, however, are far from uniform, and the best reports quote a range of 50% to 75% success in providing satisfactory pain relief. In recent years, there has been considerable success in treating various movement disorders, particularly in Parkinson's disease (PD) and dystonia, by chronic high-frequency DBS of nuclear structures in the basal ganglia. This technique has also been shown to be relatively effective in some selected cases of tremulous conditions like essential tremor and posttraumatic tremor. However, when the same techniques have been applied to patients with multiple sclerosis tremor (MST), the results have been mixed. As a result, DBS for MST has often been perceived as an unreliable and inconsistent therapeutic intervention. The authors present their experience with the application of DBS in these two relatively unpopular areas for neuromodulation in the current practice of functional stereotactic neurosurgery. The results demonstrate that with careful patient selection, DBS can offer significant functional benefit in both of these difficult clinical conditions.

Brain Mapping↗

Assessments of axial motor control during deep brain stimulation in parkinsonian patients.

OBJECTIVE: We tested the hypothesis that bilateral deep brain stimulation (DBS) in the globus pallidus internus or the subthalamic nucleus improves various components of postural and oromotor function and that some of the components correlate with changes in the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease. METHODS: Six patients with Parkinson's disease were evaluated for four postural and two orofacial UPDRS items, and quantitative tests of posture adjustments and oromotor control were performed while the patients were on and off DBS. Measurements of postural adjustments included reactive force and latency before a voluntary step. The oromotor assessments involved velocity and amplitude changes during voluntary jaw movement. RESULTS: DBS significantly improved the total UPDRS motor score by an average of 44%, which included improvement of 18 to 54% in the postural and orofacial items. DBS also decreased foot lift-off latency significantly, but it produced a variable response to the preparatory postural force in the swing limb. DBS significantly improved jaw-opening velocity by 14 to 50% and jaw opening amplitude by 5 to 41%. Significant correlations for the percentage change from off and on DBS occurred among a few UPDRS items and foot lift-off latency and jaw-opening velocities. CONCLUSION: DBS in either the globus pallidus internus or the subthalamic nucleus induces improvements in bradykinesia of specific components of postural and oromotor control, which also can be measured by the postural and orofacial UPDRS items. In some Parkinson's disease patients, DBS results in improvements in force or amplitude control, although these changes are not reflected in changes in UPDRS postural and orofacial items. A battery of quantitative and clinical tests must be used to evaluate the effects of DBS on axial motor control adequately.

Electric Stimulation↗

Panic and fear induced by deep brain stimulation.

BACKGROUND: Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region. OBJECTIVE: To investigate panic and fear resulting from DBS. METHODS: Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions. RESULTS: DBS at the distal (0) contact (cathode 0-, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off condition CONCLUSIONS: DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks.

Anxiety↗

Vocal tremor reduction with deep brain stimulation.

We present a case illustration of the significant effect that deep brain stimulation (DBS) of the thalamus can have on vocal tremor. A 72-year-old female with a history of essential tremor was noted preoperatively to have a moderate vocal tremor (3 on a scale of 1-5). Following bilateral DBS of the thalamus, the vocal tremor rating improved to 1. Acoustic analysis demonstrated her vocal tremor to be affecting the amplitude of her voice at 5.58 Hz preoperatively, at 1. 93 Hz postoperatively with both leads on and at 1.54 Hz with only the left lead on. A videotaped endoscopic view of the patient's vocal cords (presented at the 1999 ASSFN meeting) clearly illustrated the dramatic changes apparent in the vocal tremor when the stimulators were turned on and off.

Aged↗