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PubMed2005

Hardware-related complications of deep brain stimulation: a ten year experience.

OBJECTIVE: To analyse the occurrence of hardware-related complications in patients with deep brain stimulation (DBS), over a long period of time. METHOD: All patients operated on with DBS at our institution between 1993 and 2002 were followed with respect to adverse events related to the implanted hardware. RESULTS: One hundred and nineteen consecutive patients underwent 139 procedures with implantation of 161 electrodes. The minimum follow-up was 12 months. The follow-up time was 540 electrode-years. The rate of hardware-related complications per electrode-year was 4.3%. In total, 17 patients (15%) had 23 hardware-related complications. These included 8 electrode breakages, 4 electrode migrations, 2 stimulator migrations, 3 erosions, 2 erosions and infections, 2 infections and 2 cases of stimulator malfunction. The majority of these complications occurred during the first four years in our experience. CONCLUSIONS: DBS is a life-long therapy that requires a life-long follow-up. Increased experience and adaptation of surgical technique are the main determinants for avoidance of hardware-related complications.

Adult↗

PubMed2005

Deep brain stimulation in late stage Parkinson's disease: a retrospective cost analysis in Germany.

During the last few years, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as a promising therapy, alleviating major motor symptoms of Parkinson's disease (PD). However, in times of growing budgetary limitations, medical decisions are no longer merely based on clinical efficacy, but also on cost-effectiveness. Here we assess treatment costs (i. e. costs for conservative pharmacological treatment and all in-patient admissions) of 46 PD patients for one year before and two years after STN-DBS. The present data show that total treatment costs were increased by 32% for the first year and decreased by 54% for the second year of STN-DBS in comparison with preoperative values while the Unified Parkinson's Disease Rating Scale (UPDRS III) was significantly improved. The increase for the first year after surgery was mainly due to the implantation of the STN electrodes and the stimulation device. Taken together, STNDBS pays off from the second year of stimulation while motor symptoms are significantly improved. The present study provides first data of an important number of patients on clinical effectiveness and expenses in relation to STNDBS.

Analysis of Variance↗

PubMed2003

Two-year follow-up of subthalamic deep brain stimulation in Parkinson's disease.

We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) who were evaluated 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS) in a standardized levodopa test. Additional follow-up was available in 32 patients after 12 months and in 20 patients after 24 months. At 6 months follow-up, STN-DBS reduced the UPDRS motor score by 50.9% compared to baseline. This improvement remained constant at 12 months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN-DBS included intraoperative subdural hematoma without neurological sequelae (n = 1), minor intracerebral bleeding with slight transient hemiparesis (n = 1), dislocation of impulse generator (n = 2), transient perioperative confusional symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic behaviour (n = 2), and transient manic psychosis (n = 1). One patient died because of heart failure during the first postoperative year. The current series demonstrates efficacy and safety of STN-DBS beyond the first year after surgical procedure. Complications of STN-DBS comprise a wide range of psychiatric adverse events which, however, were temporary.

Electric Stimulation↗

PubMed2003

Deep brain stimulation in dystonia.

Renewed interest in stereotaxy for dystonia followed the introduction of deep brain stimulation (DBS) in Parkinson's disease and essential tremor in the 1990s. DBS evolved from ablative surgery, which was applied with varying results in the 1950s in patients with movement disorders such as Parkinson's disease, essential tremor and dystonia. The present review summarizes the current knowledge on clinical aspects of DBS in dystonia (Dec. 2002). Excellent results have been achieved in dystonic patients carrying a mutation in the DYT1 gene with improvements up to 90 %. Similar results may also be obtained in patients with idiopathic generalized dystonia, myoclonus-dystonia syndrome, and tardive dystonia. Substantial improvement has been observed in patients with focal dystonia (for instance cervical dystonia). Patients with secondary dystonia often display a lesser and more variable degree of improvement. Long-term studies are warranted to assess both motor and neuropsychological sequelae of DBS in dystonia. Furthermore, the optimal target for different dystonic disorders remains to be determined, although the globus pallidus internus has currently emerged as the most promising target for dystonia.

Dystonia↗

PubMed2001

Non-motor effects of deep brain stimulation of the subthalamic nucleus in Parkinson's disease: preliminary physiological results.

Although deep brain stimulation (DBS) is a clinically effective therapy for patients with advanced Parkinson's disease (PD), its physiological effects on the brain and possible actions on non-motor functional systems remain largely unknown. This study evaluated the effects of DBS of the subthalamic nucleus (STN) on neurophysiological variables and on cardiovascular physiology. Nine patients affected by PD undergoing chronic DBS of the STN have been studied. We performed electroencephalography (EEG), somatosensory (SEPs) and visual evoked potentials (VEPs), exteroceptive masseteric silent period and sympathetic skin response (SSR) studies with DBS ON and OFF. To assess the effects of stimulation on the cardiovascular system the tilt test and plasma renin activity were studied. When we turned the DBS OFF, both SEP N20 and the VEP P100 component increased significantly in amplitude whereas the SSR decreased in amplitude and increased in latency. Although plasma renin activity tended to increase with DBS OFF, its modification induced by postural changes and blood pressure values did not significantly differ with DBS ON and OFF. We conclude that DBS of the STN in PD, besides inducing a clinical improvement, induces several non-motor effects.

Afferent Pathways↗

PubMed2003

Intracranial volume conduction of cortical spikes and sleep potentials recorded with deep brain stimulating electrodes.

OBJECTIVE: To examine interictal epileptiform and sleep potentials recorded intracranially from deep brain stimulation (DBS) electrodes in patients treated with DBS for epilepsy. Specifically, this study sought to determine whether the DBS-recorded potentials represent: (a) volume conduction from surface neocortical discharges or (b) transsynaptic propagation along cortical-subcortical pathways with local generation of the subcortical potentials near the DBS targets. METHODS: Six patients with intractable epilepsy treated with thalamic DBS of the central median nucleus (CM; one patient) or anterior thalamus (5 patients) who had focal interictal spikes were studied. Sleep potentials were also studied in a 7th patient with Parkinson disease treated with DBS of the subthalamic nucleus (STN). RESULTS: Focal interictal cortical spikes recorded by scalp electroencephalography (EEG) were recorded synchronously, but with opposite polarity, from the DBS electrodes in CM as well as the more superficial anterior thalamic contacts situated in the anterior nucleus (AN) and dorsal medial nucleus (DM). In referential montages, the subcortical potentials were of highest amplitude ipsilateral to the focal cortical spikes, with a small but reproducible amplitude decrement present at each electrode contact more distant from the cortical source, irrespective of the specific DBS target. Subcortical sleep potentials (K-complexes and sleep spindles) were also recorded synchronously and with inverse polarity compared to the corresponding scalp potentials, and appeared in a similar fashion at all subcortical sites sampled by the DBS electrodes. Amplitude attenuation in the thalamus of intracranial volume conducted potentials with increasing distance from their cortical spike sources was measured at approximately 5-10 microV/mm. DISCUSSION: Recent reports on scalp-CM or scalp-STN EEG recordings in patients treated with DBS for epilepsy have interpreted the intracranial waveforms as evidence of transsynaptic cortical-subcortical transmission across neuroanatomical pathways presumed to be involved in the generation of sleep potentials (Clin. Neurophysiol. 113 (2002) 25) and epileptiform activity (Clin. Neurophysiol. 113 (2002) 1391). However, our results show that the intracranial spikes recorded from DBS electrodes in various regions of the thalamus (CM, AN and DM) represent subcortical volume conduction of the synchronous cortical spikes recorded with scalp EEG. The same is true for the intracranial reflections of scalp EEG sleep potentials recorded from DBS electrodes in CM, AN, DM and STN. These interictal DBS waveforms thus cannot be used to support hypotheses of specific cortical-subcortical pathways of neural propagation or subcortical generation of the DBS-recorded potentials associated with scalp EEG interictal spikes and sleep potentials. SIGNIFICANCE: Detailed analysis of the intracranial potentials recorded from DBS electrodes in association with scalp EEG spikes and sleep discharges shows that the intracranial waveforms represent volume conduction from discharges generated in the neocortex and not, as has been suggested, locally generated activity resulting from cortical-subcortical neural propagation.

Adult↗

PubMed2003

Longevity of batteries in internal pulse generators used for deep brain stimulation.

The longevity of batteries in internal pulse generators (IPGs) used clinically for deep brain stimulation is not known. We conducted a study to assess the life span of these batteries. From 1993 to 2000, 163 single-channel batteries were surgically implanted in our institution. The electrical settings utilized in patients who had battery failures were assessed and the total electrical energy delivered (TEED) was calculated and correlated with battery longevity. Fourteen IPGs had battery failure requiring replacement. The median life span of the batteries was 45 months. Batteries with high energy consumption as assessed by TEED had a reduced life span (r = -0.82, p < or = 0.001). Patients with essential tremor who required battery replacement needed higher settings to control their symptoms and therefore presented a shorter battery life when compared to patients with Parkinson's disease. In our series of patients who needed battery replacement, battery longevity varied with stimulation parameters but was longer than expected from the manufacturer's specifications.

Electric Power Supplies↗

PubMed1995

Deep brain stimulation for neuropathic pain.

Paresthesia-producing (PP), but not periventricular grey (PVG) deep brain stimulation (DBS) proved effective in steady neuropathic pain in 25 patients receiving both, regardless of the PP site stimulated, but PVG-DBS suppressed allodynia or hyperpathia in 3 cases of stroke-induced pain. In patients with stroke-induced central pain, PP-DBS was unpleasant in 6 of 17 (35%), all with allodynia and/or hyperpathia, but not in patients with spinal cord central or peripheral neuropathic pain with allodynia or hyperpathia. Of 11 patients in whom prior ineffective dorsal column stimulation (DCS) produced appropriate paresthesia, none responded to PP-DBS; 5 of 7 did so in whom DCS produced no paresthesia or relieved pain. Periaqueductal grey DBS was nearly always unpleasant, PVG-DBS sometimes was.

Brain↗

PubMed1999

Globus pallidus deep brain stimulation for generalized dystonia: clinical and PET investigation.

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in a patient with severe idiopathic generalized dystonia resulted in immediate improvement of all aspects of dystonia. During joystick movement, GPi DBS reduced PET activation bilaterally in the primary motor, lateral premotor, supplementary motor, anterior cingulate, and prefrontal areas and ipsilaterally in the lentiform nucleus. Altering basal ganglia function with GPi DBS reverses the overactivity of certain motor cortical areas present in dystonia.

Brain↗

PubMed2001

Lesion of thalamic centromedian--parafascicular complex after chronic deep brain stimulation.

A patient with PD who exhibited disabling tremor and prominent dyskinesia underwent deep brain stimulation (DBS) of the left thalamic ventral intermediate nucleus. The electrode migrated and was replaced but with suboptimal clinical response. Two years later, postmortem analysis found the second electrode tip had entered the thalamic centromedian-parafascicular complex. There was a small thalamotomy and cell loss exceeding that found in PD. Thalamic damage may occur in association with DBS for PD.

Chronic Disease↗

PubMed2001

Interactions between deep brain stimulation and levodopa in Parkinson's disease.

OBJECTIVE: To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. BACKGROUND: Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but this has not been objectively measured. Further, the means by which DBS alters the response to levodopa to improve motor fluctuations is unknown. METHODS: Twelve subjects, six with bilateral GPi electrodes and six with bilateral STN electrodes, were studied 12 to 33 months after surgery. To quantify motor fluctuations and dyskinesia, subjects were monitored hourly throughout 2 waking days with their usual oral medications, 1 day with DBS on and 1 day with DBS off, with subjects and nurse raters blinded to DBS status. To examine the effects of DBS on levodopa pharmacodynamics, the effects of a 2-hour levodopa infusion were examined, 1 day with DBS on and 1 day with DBS off, again under double-blind conditions. Time course of variations in parkinsonism was evaluated by tapping speed, arising and walking speed, tremor scores, and dyskinesia scores. RESULTS: DBS raised the mean tapping speed and reduced the coefficient of variation during the waking day. This was achieved by increasing the lowest or trough tapping speed between doses of antiparkinson medications. Mean walking speed was modestly increased and mean tremor scores were reduced. DBS increased the drug-off tapping speed, but neither the peak response nor the duration of response to levodopa was affected by DBS. The study was not powered to detect differences between GPi and STN stimulation and the only difference that approached significance was that GPi reduced peak dyskinesia and STN tended to increase peak dyskinesia. CONCLUSION: DBS objectively reduces motor fluctuations. This is achieved by reduction of drug-off disability and not by alterations in levodopa pharmacodynamics. This finding suggests alleviation of interdose trough disability as an alternative strategy to prolonging the effects of each dose of levodopa as a means to reduce motor fluctuations.

Adult↗

PubMed2002

Magnetic resonance imaging and deep brain stimulation.

OBJECTIVE: To determine whether cranial magnetic resonance imaging (MRI) is associated with deep brain stimulation (DBS) lead displacement or program interference. METHODS: In vitro and in vivo studies were performed with the Itrel II implantable pulse generator (IPG) (Model 7424; Medtronic, Minneapolis, MN), Medtronic 3387 and 3389 leads, and a 1.5-T GE Horizon LX scanner (General Electric, Milwaukee, WI). In the in vivo study, two MRI volumetric data sets were compared for each of five patients undergoing staged, bilateral, DBS electrode placement in the thalamic or subthalamic nucleus. The data sets were acquired shortly after the initial implantation and during stereotactic planning for the second implantation (1-8 mo between acquisitions). An additional thalamotomy-treated patient was included as a control patient. Volumetric data were analyzed in a blinded manner, using AnalyzeAVW 3.0 software (Biomedical Imaging Resource, Mayo Clinic, Rochester, MN), to determine lead movement. In the in vitro study, the IPG and leads were positioned in the magnetic field in various configurations and were systematically assessed for movement. RESULTS: In vivo, the majority of measured deviations (88%) were within the standard error of measurement (1.4 mm). The maximal measured deviation was 3 mm (2% occurrence). Excellent tremor control with stimulation was demonstrated, which did not change after MRI. In vitro, the DBS leads demonstrated no deflection when introduced into the magnetic field. Similarly, no changes in IPG battery strength, lead impedance, or program settings were observed. CONCLUSION: MRI was not associated with significant DBS electrode movement or changes in clinical responses. Other IPG models and components and MRI scanners should be evaluated, to develop specific guidelines for MRI among individuals with implanted DBS systems.

Electric Stimulation Therapy↗

PubMed2004

[Mental competence in the context of deep brain stimulation].

In a case of Parkinson's disease, the patient was treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). STN-DBS affected the mental competence of the patient and ethical questions were raised about the decision as to the direction of further treatment. The patient was asked for his opinion on the therapeutic options during a phase of non-stimulation and chose to be stimulated and admitted to a psychiatric hospital because of mental incompetence rather than remaining unstimulated, mentally competent but bedridden. Developments in the neurosciences (including STN-DBS) raise a number of different fundamental (theoretical and philosophical) as well as practical questions. STN-DBS can have various unintended (behavioural) effects. In the case presented, more weight was rightly given to the mental competence of the unstimulated patient, although comments can be made with regard to his decision making, as his choice was made in a phase of serious distress. Attention is paid to the relevance of a so-called self-binding directive. STN-DBS is not morally neutral and the case involves a tragic dilemma: a conflict between irreconcilable duties for the physician. The further development and proliferation of STN-DBS requires caution and moral deliberation. It remains important to search for alternative treatment strategies with less undesirable side effects.

Electric Stimulation Therapy↗

PubMed2005

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

OBJECTIVE: To evaluate the clinical effects of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease within the first 12 months after surgery. METHODS: We performed a prospective study in 8 patients with Parkinson's disease, in whom electrodes were implanted in the subthalamic nucleus bilaterally. We compared levodopa-equivalents and the scores of the Unified Parkinson's Disease Rating Scale pre- and post-operatively. The post-operative evaluation was done between 3 and 12 months after surgery. RESULTS: Antiparkinsonian medications were reduced post-operatively by a mean of 61.5% (P < 0.01) from a levodopa-equivalent dosage of 1144.9 +/- 572.5 mg/day to 440.9 +/- 172.1 mg/day. Motor scores improved 44.4% (P < 0.01) and activities of daily living scores 38.2% (P < 0.01). Adverse events included a subcutaneous hematoma in 1 patient after internal pulse generator implantation necessitating evacuation. CONCLUSIONS: Bilateral stimulation of the subthalamic nucleus is associated with significant improvement in motor function and reduction of antiparkinsonian medications in patients with Parkinson's disease in the first 12 months after surgery. On-state dyskinesias were greatly reduced, probably due to the reduction of total antiparkinsonian medications. The procedure is well tolerated.

Aged↗

PubMed2005

Risk factors for hemorrhage during microelectrode-guided deep brain stimulator implantation for movement disorders.

OBJECTIVE: Although hemorrhage is a well-known complication of microelectrode-guided deep brain stimulation (DBS) surgery, risk factors for the development of hemorrhage have not been well defined. We analyzed the risk factors for symptomatic and asymptomatic hemorrhage in a large series of DBS implantations into the subthalamic nucleus, ventrolateral thalamus, and internal globus pallidus. METHODS: All DBS procedures performed by a single surgeon at our institution between June 1998 and May 2004 were included in this study. All patients had postoperative imaging (magnetic resonance imaging or computed tomography) 4 to 24 hours after surgery. Hematomas were noted and scored as symptomatic or asymptomatic. Statistical correlation of factors affecting risk of hematoma formation was performed by use of logistic regression analysis. RESULTS: The total number of lead implantations was 481. There were 6 symptomatic hematomas and 10 asymptomatic hematomas. Three of the symptomatic hematomas resulted in permanent new neurological deficit. The risk of hematoma (of any type) per lead implantation was 3.3%, whereas the risk of permanent deficit from hematoma was 0.6%. Patients who developed hematomas had a slightly greater number of microelectrode recording penetrations than patients who did not have hematomas, but this difference did not reach statistical significance. There was not a statistically significant relationship between risk of hematoma and patient age or diagnosis. There was a significant effect of brain target (P = 0.001), with only 1 hemorrhage detected after thalamic DBS. CONCLUSION: DBS is generally safe, with only 0.6% of implantations associated with permanent neurological deficit. The incremental risk of successive serial microelectrode penetrations is small.

Aged↗

PubMed2000

A program for neuropsychological investigation of deep brain stimulation (PNIDBS) in movement disorder patients: development, feasibility, and preliminary data.

OBJECTIVE: This technical report and feasibility study propose a standardized method for collecting neuropsychological data in patients undergoing the deep brain stimulation (DBS) procedure. BACKGROUND: Programs for standardizing motor data collected in studies investigating surgical therapies for Parkinson disease are already widely used (e.g., Core Assessment Program for Intracerebral Transplantations). The development and rationale for the proposed Program for Neuropsychological Investigation of Deep Brain Stimulation (PNIDBS) are outlined, and support for the feasibility of these methodologies is provided via preliminary data. METHOD: The PNIDBS includes a core battery of neuropsychological tests that assesses a wide range of cognitive functions (attention, language, visuospatial, memory, and executive) as well as depression. Using the PNIDBS, three Parkinson disease and two dystonia patients were evaluated at baseline and after surgery, once with stimulation off and once with stimulation on. RESULTS: Patients with severe motor disabilities were able to complete the PNIDBS. These preliminary data suggest that the DBS procedure as a whole had a minimal impact on cognitive functioning in most patients studied. There was also some evidence that the one patient who showed cognitive decline after the DBS procedure had demographic and clinical characteristics that may have put him at risk for this decline. CONCLUSIONS: The procedures in the PNIDBS were systematically developed and are feasible to execute. The relatively brief core battery has multiple versions and can be supplemented to meet individual investigator needs. By evaluating the components of the DBS procedure (electrode placement and stimulation), the PNIDBS can address clinical questions regarding the cognitive effects of the DBS procedure as well as investigate basic scientific issues regarding how different cognitive functions are affected when subcortical-prefrontal circuits are manipulated by the DBS procedure.

Brain↗

PubMed2006

Does subthalamic nucleus deep brain stimulation really improve quality of life in Parkinson's disease?

We investigated the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on quality of life (QOL) in patients with advanced Parkinson's disease, as self-assessed before and after surgery by completing the Parkinson's Disease Questionnaire (PDQ39). In addition to this prospective evaluation, we asked patients postoperatively to evaluate their preoperative QOL. In the prospective assessment, results showed that patients perceived a general improvement of QOL after the STN DBS. However, when evaluated retrospectively, they tended to overestimate their preoperative functioning, therefore obscuring the improvement found prospectively. This observation highlights the impact of the method used on obtained results when assessing the effects of STN DBS.

Activities of Daily Living↗

PubMed1999

Improvement of levodopa induced dyskinesias by thalamic deep brain stimulation is related to slight variation in electrode placement: possible involvement of the centre median and parafascicularis complex.

OBJECTIVE: To define the reason why two teams using the same procedure and the same target for deep brain stimulation (DBS) obtained different results on levodopa induced dyskinesias, whereas in both, parkinsonian tremor was improved or totally suppressed. METHODS: Deep brain stimulation can replace lesions in the surgical treatment of abnormal movements. After 10 years of experience with DBS in Parkinson's disease, a comparison of results between the teams of Lille (A) and Grenoble (B) was carried out, for as long as they used intraoperative ventriculography. Both teams aimed at the same target, the ventralis intermedius nucleus of the thalamus (VIM), but team A found a clear improvement of choreic peak dose dyskinesias, whereas team B did not consistently. Therefore all teleradioanatomical data of both teams were re-examined and compared with the therapeutic effects. Location of 99 monopolar electrodes of thalamic stimulation applied to treat parkinsonian tremor has been retrospectively measured (team A included 21 patients, 22 electrodes; team B included 52 patients, 74 electrodes). Peak dose levodopa dyskinesias were suppressed by DBS in all nine patients of team A, four of which were severely disabling. Only eight out of 32 patients from team B experienced a moderate (four) or clear (four) improvement of dyskinesias, whereas in the remaining 24 patients, dyskinesias were unchanged with stimulation. RESULTS: The mean centre of team A's electrodes was on average 2.9 mm deeper, more posterior and medial than team B's (t=8.05; p<0.0001). This does not correspond to the coordinates of the VIM, but seems to be closer to those of the centre median and parafascicularis complex (CM-Pf), according to stereotaxic atlases. Considering only the dyskinetic patients, significant differences were found in the electrode position according to the therapeutic effects on levodopa dyskinesias, but they were not related to the team membership. Improvement in levodopa dyskinesias was significantly associated with deeper and more medial placement of electrodes. CONCLUSION: The retrospective analysis of patients treated with DBS using comparable methodologies provides important information concerning electrode position and therapeutic outcome. The position of the electrode is related to the therapeutic effects of DBS. The results support the hypothesis that patients experiencing an improvement of dyskinesias under DBS are actually stimulated in a structure which is more posterior, more internal, and deeper than the VIM, very close to the CM-Pf. These results are consistent with neuroanatomical and neurophysiological data showing that the CM-Pf is included in the motor circuits of the basal ganglia system and receives an important input from the internal pallidum. This suggests that the CM-Pf could be involved specifically in the pathophysiology of levodopa peak dose dyskinesias.

Aged↗