Systems for deep brain stimulation: review of technical features.

The use of deep brain stimulation (DBS) is an important treatment option for movement disorders and other medical conditions. Today, three major manufacturers provide implantable systems for DBS. Although the underlying principle is basically the same for all available systems, the differences in the technical features vary considerably. This article outlines aspects regarding the technical features of DBS systems. The differences between voltage and current sources are addressed and their effect on stimulation is shown. To maintain clinical benefit and minimize side effects the stimulation field has to be adapted to the requirements of the patient. Shaping of the stimulation field can be achieved by the electrode design and polarity configuration. Furthermore, the electric signal consisting of stimulation rate, stimulation amplitude and pulse width affect the stimulation field. Interleaving stimulation is an additional concept, which permits improved treatment outcomes. Therefore, the electrode design, the polarity, the electric signal, and the concept of interleaving stimulation are presented. The investigated systems can be also categorized as rechargeable and non-rechargeable, which is briefly discussed. Options for interconnecting different system components from various manufacturers are presented. The present paper summarizes the technical features and their combination possibilities, which can have a major impact on the therapeutic effect.

Ventral intermediate thalamic stimulation in complex tremor syndromes.

BACKGROUND/AIMS: We report on deep brain stimulation (DBS) in the ventral intermediate part of the thalamus in 4 patients with complex tremor syndromes, 2 classified as Holmes tremor (HT) and 2 as thalamic tremor (TT). RESULTS: Three out of 4 patients showed intraoperative improvement and underwent DBS implantation. One patient with TT without intraoperative improvement was not provided with an implant. A sustained beneficial effect was present after a follow-up ranging from 20 months to 7 years, although there was partial persistence of the intentional tremor and of proximal myoclonic-dystonic movements. The mean global clinical impression score was 2. In 1 HT patient the benefit persisted after battery failure. CONCLUSION: The study confirms that ventral intermediate thalamic DBS can provide long-term efficacy for HT and TT. While the patients experienced considerable and lasting functional improvement, the effect was incomplete and not all elements of their complex movement disorders were equally suppressed.

Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up.

AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery. METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation. RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

Influence of bilateral Stn-stimulation on psychiatric symptoms and psychosocial functioning in patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. There is some evidence that subthalamic stimulation not only affects motor function, but also mood, behaviour and cognition. In the present study we investigated the effects of subthalamic stimulation on psychiatric symptoms and psychosocial functioning in a consecutive series of patients with Parkinson's disease. 33 patients were assessed three times prior to surgery and at three, nine weeks as well as three, six and twelve months after surgery. We found significant improvements in depression, anxiety, psychological symptoms and distress after surgery. In most cases the amelioration followed surgery and was stable in the course of time. Individual analysis indicated deterioration in three patients despite motor improvement. The results suggest that stimulation of the subthalamic nucleus has a positive influence on psychiatric symptoms, psychosocial functioning and distress. We observed a decline in a minority of patients.

Kinematic evaluation in Parkinson's disease using a hand-held position transducer and computerized signal analysis.

BACKGROUND: The objective of this work was to develop a device for quantification of akinesia in Parkinson's disease, for the use in home monitoring of PD patients, as a part of home telecare programs. For this purpose a simple movement task is to be preferred, and the measurement devices must be small, lightweight, and easy to use, so patients may perform the measurements unattended. Another intended application was optimisation of the electrode position during implantations of neuromodulation systems for treatment of Parkinson. METHOD: A hand held transducer was used to measure the position of the thumb while the patient repeatedly flexed and extended the thumb. The position data was sampled and stored on a personal computer with a plug in converter card and software. Measurements were performed on 15 PD patients and 6 age-matched controls. Signal analysis procedures were developed in order to automatically derive numerical parameters that quantify the movement performance. In order to select the most relevant parameters, they were correlated to Unified Parkinson Disease Rating Scale (UPDRS) motor scores (Spearman's rank, single sided, p < 0.05). FINDINGS: In reviews of the raw position signals the amplitude and frequency was found to be lower in patients than in controls. In patients the movement was frequently interrupted by short periods of hesitation. The calculated parameters of covered distance (correlation coefficient r = -0.63), hesitation (r = 0.64) and frequency (r = -0.6) were found to be most relevant, as they correlated best to the UPDRS hand pronation/supination score. DISCUSSION: The equipment proved to be fast to setup and easy to use. The signal analysis methods provided meaningful numerical parameters for quantification of akinesia, represented in hand pronation/supination. These results suggest that the described methods may be useful for telemedicine and intraoperative use.

Treatment of severe tardive dystonia with pallidal deep brain stimulation.

In five patients with medically refractory tardive dystonia, continuous bilateral high-frequency stimulation of the globus pallidus internus was associated with a rapid (within 12 to 72 hours) and substantial (mean 87%, 10.7 SD of the motor part of the Burke-Fahn-Marsden Dystonia Rating Scale) improvement of dystonia and functional disability without adverse events.

Multicentre European study of thalamic stimulation in essential tremor: a six year follow up.

BACKGROUND: Thalamic stimulation is an efficient treatment for disabling essential tremor, as previously shown, but follow up has mostly been short term. OBJECTIVES: To see whether good results can be maintained in the longer term. METHODS: 37 patients with essential tremor had implantation of a thalamic stimulator, either unilaterally or bilaterally. The results at one year have been reported earlier. After six years, 19 patients were available for follow up. The main instrument for evaluation was the essential tremor rating scale. The patients were examined with pulse generators turned on and off. RESULTS: In the majority of patients, the very good results with stimulation seen at one year were maintained after a mean of 6.5 years. The reduction in tremor scores and improvement in activities of daily living were highly significant compared with baseline and with the stimulation turned off. There were few serious adverse events. Minor side effects related to stimulation were common. Few device related complications were observed and most could be resolved. CONCLUSIONS: Good reduction in tremor can be maintained for more than six years in the majority of these severely disabled patients. Thalamic stimulation can be recommended in essential tremor where there is insufficient response to drug treatment. Surgical procedures and follow up should be concentrated in relatively few centres, which will thereby acquire a high degree of expertise.

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.

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

Bilateral subthalamic nucleus stimulation does not improve prolonged P300 latencies in Parkinson's disease.

Bilateral deep brain stimulation is an effective treatment for most motor signs of Parkinson's disease (PD), but the effects on cognitive functions are less clear. We therefore examined the effects of bilateral deep brain stimulation on central information processing, using the event-related auditory P300 potential as an electrophysiological index of mental chronometry. Eight PD patients with bilateral stimulators within the subthalamic nuclei (STN) and eight age-matched controls participated. Patients were examined after overnight withdrawal of antiparkinson medication, both "on" and "off" stimulation (in random sequence). The P300 and reaction times were recorded using an auditory oddball paradigm. P300 latencies were prolonged in PD patients off stimulation (440 +/- 45 ms) compared to controls (397 +/- 16 ms; P < 0.05). STN stimulation significantly reduced clinical disease severity (as indexed by the Unified Parkinson's Disease Rating Scale) and markedly improved reaction times, but did not improve the prolonged P300 latencies in PD patients (429 +/- 36 ms). These results confirm that P300 latencies are prolonged in PD. Significantly, bilateral STN stimulation did not improve this electrophysiological measure of cognitive impairment, even though motor disability was markedly reduced. This suggests that some dopa-responsive features are resistant to STN stimulation, possibly due to involvement of dopaminergic deficits outside the nigrostriatal pathway, which are not influenced by outflow from the STN.

Electromagnetic compatibility of electronic implants--review of the literature.

The aim of the article was to provide an overview of published studies regarding the electromagnetic compatibility (EMC) of electronic implants. The available literature was sorted according to combinations of implant types and sources of interference. Several experiments concerning the susceptibility of pacemakers to mobile phones have been performed. The results of these experiments suggest measures that may be used to prevent the disturbance of pacemakers. For instance, instead of carrying the activated mobile phone in the breast pocket it is recommended that a distance of 30 cm be maintained between the pacemaker and the mobile phone, and that the mobile phone be used on the contralateral side of the pacemaker's location. Similar measures may be recommended for patients with implantable cardioverter defibrillators when using mobile phones. Patients with electronic implants should walk rapidly through anti theft-devices because some of these devices are liable to disturb implants. Patients with cardiac pacemakers should not be subjected to magnetic resonance imaging as far as possible. For a variety of combinations of implants and interference sources, e.g. cardiac pacemakers and base station antennas, no studies were found in the literature. It is strongly recommended that trials be carried out to evaluate the potential risk for patients in these settings.

No tissue damage by chronic deep brain stimulation in Parkinson's disease.

We report on the pathological findings in the brains of 8 Parkinson's disease patients treated with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (6 cases) and subthalamic nucleus (2 cases). DBS was performed continuously for up to 70 months. All brains showed well-preserved neural parenchyma and only mild gliosis around the lead track compatible with reactive changes due to surgical placement of the electrode. We conclude that chronic DBS does not cause damage to adjacent brain tissue.

Visual hallucinations induced by deep brain stimulation in Parkinson's disease.

We report a patient with idiopathic Parkinson's disease who underwent bilateral deep brain stimulation (DBS) of the nucleus subthalamicus (STN) and developed visual hallucinations (VH) while taking no medications only when the DBS was turned on. The hallucinations resolved when the stimulator was turned off. The phenomenology and the prompt response to clozapine suggest that DBS-induced VH mimic pharmacologically-induced VH.

Does deep brain stimulation of the nucleus ventralis intermedius affect postural control and locomotion in Parkinson's disease?

The purpose of this study was to evaluate the effect of unilateral stimulation of the nucleus ventralis intermedius (VIM) on parkinsonian signs like postural stability and locomotion with respect to the severity of Parkinson's disease (PD). Seven patients with idiopathic PD were included in the study. Changes in visual cues on postural stability and step initiation were assessed on a fixed platform system with VIM stimulation switched either on (VIM ON) or off (VIM OFF), and compared with a control group of seven age-matched normal individuals. Sway scores (area and path) were significantly (p <0.05) higher in the parkinsonian patients with VIM OFF than with VIM ON as well as compared with the control subjects. No correlation was obtained between extent of sway scores and severity of contralateral tremor after cessation of VIM stimulation. Locomotion parameters, by contrast, were not influenced by VIM stimulation: latency until step initiation and walking-cycle time were the same among parkinsonian patients as among normal individuals, both in the presence and in the absence of VIM stimulation. In conclusion, our results indicate that tremor suppression by VIM stimulation improves postural stability.

Changes in handwriting resulting from bilateral high-frequency stimulation of the subthalamic nucleus in Parkinson's disease.

High-frequency stimulation of the subthalamic nucleus (STN) is a promising therapeutic approach in patients with severely disabling Parkinson's disease (PD). Whereas STN stimulation improves the cardinal signs of PD, little is known about the effects of STN stimulation on fine manual skills like handwriting. Therefore, the present study investigated the changes in handwriting during bilateral STN stimulation in 12 patients with advanced PD. Dopaminergic medication was discontinued at least 12 hours before the study. The patients were asked to write a standardized sentence repetitively. Five samples of the patient's script were recorded during effective bilateral STN stimulation and 1 hour after both stimulators had been switched off. The movements of the tip of the pencil were recorded using a digitizing tablet. Handwriting movements were segmented into subsequent up- and down-strokes, and a stroke-based kinematic analysis of handwriting was performed. During high-frequency STN stimulation, handwriting movements became faster and smoother indicating a partial restoration of an "open-loop" automatic performance. In addition, STN stimulation gave rise to a significant increase in the mean vertical stroke length demonstrating a stimulation-related reduction in micrographia. The present data underscores the importance of the STN in "open-loop" performance of highly skilled sequential hand movements.

Bilateral subthalamic nucleus stimulation improves frontal cortex function in Parkinson's disease. An electrophysiological study of the contingent negative variation.

Parkinson's disease involves impaired activation of frontal cortical areas, including the supplementary motor area and prefrontal cortex, resulting from impaired thalamocortical output of the basal ganglia. Electrophysiologically, such impaired cortical activation may be seen as a reduced amplitude of the contingent negative variation (CNV), a slow negative potential shift reflecting cognitive processes associated with the preparation and/or anticipation of a response. Surgical interventions aimed at increasing basal ganglia-thalamic outflow to the cortex, such as electrical stimulation of the subthalamic nucleus with chronically implanted electrodes, have been shown to be effective in improving the clinical symptoms of Parkinson's disease. This study examined changes in cortical activity, as reflected in the CNV, associated with bilateral subthalamic nucleus stimulation in Parkinson's disease. The CNV was recorded from 10 patients with Parkinson's disease when on and off bilateral subthalamic nucleus stimulation, and was compared with the CNV of 10 healthy control subjects. Without subthalamic nucleus stimulation, Parkinson's disease patients showed reduced CNV amplitudes over the frontal and frontocentral regions compared with control subjects. With bilateral subthalamic nucleus stimulation, however, CNV amplitudes over the frontal and frontocentral regions were significantly increased. Results therefore suggest that impaired cortical functioning in Parkinson's disease, particularly within the frontal and premotor areas, is improved by subthalamic nucleus stimulation.

Apomorphine test: a predictor for motor responsiveness to deep brain stimulation of the subthalamic nucleus.

The value of the apomorphine test as a predictor of the clinical outcome of deep brain stimulation of the subthalamic nucleus (STN) was evaluated in patients with advanced idiopathic Parkinson's disease (IPD) or multiple system atrophy (MSA). Thirteen IPD patients with severe diurnal fluctuations and one MSA patient not responding to dopaminergic drugs were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) and the timed finger tapping test (FTT), measured preoperatively on and off apomorphine and postoperatively on and off STN stimulation. UPDRS motor items 20-25 were assessed intraoperatively on and off STN stimulation when the clinically effective target was approached. The motor response to immediate intraoperative and long-term STN stimulation was correlated with results of the apomorphine test. The response to immediate intraoperative STN stimulation was accurately predicted by apomorphine challenge in all 13 IPD patients. Clinical outcome following long-term STN stimulation was correlated significantly with preoperative changes due to apomorphine measured with the UPDRS motor scores (r = 0.7125, P < 0.01) and FTT (r = 0.9276, P < 0.001). Moreover, comparison of long-term STN stimulation to preoperative drug treatment displayed a significant reduction in the duration of off-phases and a significant increase in the duration of on-phases. However, in the single patient with MSA no beneficial response was obtained either to apomorphine or to STN stimulation intraoperatively and during the postoperative externalized test period. Our results indicate that the apomorphine test can predict the outcome of immediate and long-term STN stimulation and may help in the selection of candidates for surgery.

A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity.

BACKGROUND: Long-term high-frequency stimulation of the subthalamic nucleus (STN) improves akinesia in Parkinson disease. The neural correlates of STN stimulation are not well understood. Positron emission tomography can be applied to the in vivo study of the mechanisms of deep brain stimulation. OBJECTIVE: To study changes in regional cerebral blood flow as an index of synaptic activity in patients with Parkinson disease with effective STN stimulation on and off during rest and movement. METHODS: Eight patients with Parkinson disease who had electrodes implanted in the STN underwent 12 measurements of regional cerebral blood flow with water O 15 positron emission tomography at rest and during performance of paced freely selected joystick movements, both with and without STN stimulation (3 scans per experimental condition). Motor performance and reaction and movement times were monitored. Statistical parametric mapping was used to compare changes in regional cerebral blood flow between conditions and differences in activation. RESULTS: All patients showed improvement in reaction and movement times during scans with the stimulator on. As predicted, increases in activation of rostral supplementary motor area and premotor cortex ipsilateral to stimulation were observed when stimulation was on during contralateral movement (P<.001). Unpredicted observations included decreases in regional cerebral blood flow in primary motor cortex at rest induced by STN stimulation. CONCLUSION: Stimulation of the STN reduces the movement-related impairment of frontal motor association areas and the inappropriate motor cortex resting activity in Parkinson disease.

Deep brain stimulation of the subthalamic nucleus for control of extrapyramidal features in advanced idiopathic parkinson's disease: one year follow-up.

UNLABELLED: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar electrode was carried out in 9 patients with advanced idiopathic Parkinson's disease (PD) affected with severe diurnal motor fluctuations. The effect of bilateral STN stimulation was evaluated by clinical methods in all patients after 3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily Living and a diary chart to document motor fluctuations. Alterations in parkinsonian signs, motor performance and functional outcome were recorded postoperatively (1) under temporary complete withdrawal of both STN stimulation and medication; (2) in the presence of STN stimulation only; and (3) in the presence of both STN stimulation and medication. The results were compared with the preoperative data assessed in defined on-phase and defined off-phase. STN stimulation on (compared to STN stimulation off) results in a significant improvement in UPDRS motor scores: after 3 months from 50.5 +/- 14.3 to 27.8 +/- 5.8, and after 12 months from 49.4 +/- 14.1 to 27.1 +/- 7.1 (p < 0.01). There was a significant decrease in the average duration of off-periods from 8.82 +/- 2.47 hours to 1.00 +/- 1.06 hours (p < 0.001), a marked increase in on-periods without dyskinesia from 4.62 +/- 2.72 to 14.62 +/- 1.51 hours (p < 0.01), and a sharp drop in on-periods with dyskinesia from 2.87 (+/- 4.18) to 0.25 (+/- 0.97) hours (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 +/- 1.58 hours, p < 0.001; on-periods without: 13.87 +/- 1.95 hours, p < 0.001; and on-periods wth dyskinesia: 0.37 +/- 1.06 hours, p < 0.05). However, our first PD patient with an implanted DBS electrode within the STN died from cardiac infarction two days after surgery. This sudden death was not linked either to surgery nor to stimulation - and happened by chance. Our findings confirm that STN stimulation is a suitable functional neurosurgical procedure for the modulation and control of PD signs associated with severe motor fluctuations, in that they demonstrate a beneficial effect which was fully sustained over a one year follow-up period. KEYWORDS: Subthalamic nucleus, deep brain stimulation, Parkinson's disease.

[Stereotactic brain biopsy in AIDS patients: a necessary patient-oriented and cost-effective diagnostic measure?]. / Die stereotaktische Hirnbiopsie bei AIDS-Patienten: eine notwendige, patientenorientierte und kosteneffektive diagnostische Massnahme?

Neurological complications occur in 40% of "human immunodeficiency virus type 1" (HIV-1)-infected patients. Aim of the study was to evaluate the diagnostic yield of stereotactic brain biopsy and non invasive diagnostic procedures (CT, antitoxoplasma antibodies) and to calculate the benefit of the brain biopsy for the patient and the costs of both methods. From October 1989 through September 1995 we biopsied 44 of 2749 (2%) HIV-1-infected patients after non invasive diagnostic procedures had been performed. In 93% of the patients an unambiguous diagnosis was possible based on the biopsy and lead in 73% of the patients to a change of therapy. No complications occurred after biopsy. 40 CTs and 15 MRIs were done. The radiological appearance of toxoplasmosis and non Hodgkin lymphoma (NHL) differed from that of progressive multifocal leucencephalopathy (PML) in respect to enhancement (PML). CT showed a sensitivity of 55% (toxoplasmosis, NHL) and 78% (PML) and a specificity of 83% (PML), 84% (NHL) and 96% (toxoplasmosis), respectively. Antitoxoplasma antibodies showed a sensitivity of 45%, only. The stereotactic brain biopsy was more expensive (20.166,- ATS) than CT, MRI and antitoxoplasma antibodies (4109,- ATS up to 6959,- ATS). We conclude that stereotactic brain biopsy is an efficient and safe and for the patients important diagnostic procedure. In selected patients even expensive investigations should be undertaken considering specific therapy and cost effective homecare.