Implantation Of Deep Brain Stimulation Electrodes Research Articles

Safety of magnetic resonance imaging of deep brain stimulator systems: a serial imaging and clinical retrospective study

With the expanding indications and increasing number of patients undergoing deep brain stimulation (DBS), postoperative MR imaging is becoming even more important in guiding clinical care and practice-based learning; important safety concerns have recently emerged, however. Although phantom model studies have driven conservative recommendations regarding imaging parameters, highlighted by 2 recent reports describing adverse neurological events associated with MR imaging in patients with implanted DBS systems, the risks of MR imaging in such patients in clinical practice has not been well addressed. In this study, the authors capitalized on their large experience with serial MR imaging (3 times per patient) to use MR imaging itself and clinical outcomes to examine the safety of MR imaging in patients who underwent staged implantation of DBS electrodes for Parkinson disease, tremor, and dystonia. Sixty-four patients underwent staged bilateral lead implantations between 1997 and 2006, and each patient underwent 3 separate MR imaging sessions subsequent to DBS placement. The first of these was performed after the first DBS placement, the second occurred prior to the second DBS placement, and third was after the second DBS placement. Follow-up was conducted to examine adverse events related either to MR imaging or to DBS-induced injury. One hundred and ninety-two MR images were obtained, and the mean follow-up time was 3.67 years. The average time between the first and second, and second and third MR imaging sessions was 19.4 months and 14.7 hours, respectively. Twenty-two MR imaging-detected new findings of hemorrhage were documented. However, all new findings were related to acute DBS insertion, whereas there were no new findings after imaging of the chronically implanted electrode. Although potential risks of MR imaging in patients undergoing DBS may be linked to excessive heating, induced electrical currents, disruption of the normal operation of the device, and/or magnetic field interactions, MR imaging can be performed safely in these patients and provides useful information on DBS lead location to inform patient-specific programming and practice-based learning.

Thalamic single‐unit and local field potential activity in Tourette syndrome

Deep brain stimulation (DBS) of the ventralis oralis (VO) complex of the thalamus improves tics in patients with Tourette syndrome (TS). To neurophysiologically describe the VO complex we recorded, in seven patients with TS undergoing DBS electrode implantation, single-unit activity during surgery and local field potentials (LFPs) a few days after surgery. Single unit recordings showed that the VO complex is characterized by a localized pattern of bursting neuronal activity. LFP spectra demonstrated that VO of TS patients has a prominent oscillatory activity at low frequencies (2-7 Hz) and in the alpha-band (8-13 Hz), and a virtually absent beta activity. In each patient, the main LFP frequency significantly correlated with single-unit interburst frequency. In conclusion, we observed an oscillatory bursting activity in the VO as target region in patients with severe TS undergoing DBS surgery.

Long‐term deep brain stimulation for essential tremor: 12‐year clinicopathologic follow‐up

We describe the clinical course and postmortem pathological findings in a patient with essential tremor (ET) treated with deep brain stimulation (DBS) for 12 years. This 75 year old woman had a 13-year history of progressive ET prior to implantation of bilateral quadripolar DBS electrodes in the region of her ventral intermediate thalamic nuclei in 1996, producing immediate relief of arm tremor. Histopathological examination of the brain, performed 12 years after the initial implantation, demonstrated electrode catheter tracts rimmed by 20-25 micron fibrous sheaths, with multinucleated giant cells and reactive gliosis. Lymphocytic infiltration was seen by L26 immunoreactivity with CD3 (T cells) staining predominating over CD20 (B cells). Cerebellar axonal spheroids and Purkinje cell loss were found. The minimal foreign body reaction and gliosis around the electrodes 12 years after implantation supports the long-term safety of DBS. The case represents the longest reported follow-up with autopsy examination after DBS and confirmed histological changes associated with ET.

Deep brain stimulation of the periaqueductal gray for treatment of nociceptive pain: tryptophan loading and the serotonergic circuit of pain

Background: Pain and pain-related diseases pose a major treatment challenge. Current medical treatments frequently provide inadequate pain control to patients, or cause dependence and other unwanted side-effects. Despite initial failures of open-label trials to show efficacy in the use of deep brain stimulation (DBS) for pain, several groups have reported utility of this modality on carefully selected patients. There are several characterized pain pathways in operation in the human brain. A common theme to the pathways thus far identified is their dependence on the neurotransmitter serotonin for modulation of pain. Deep brain stimulation for pain may well activate one of the serotonin-dependent pathways to stimulate relief. Greater experience, and improvements in both technology and patient selection, has paved the way for the potential use of electrical stimulation of subcortical structures to manage intractable and nociceptive pain syndromes and also for the mechanistic study of the pathways involved in the symptomatic relief of pain caused by stimulation. Methods: We preoperatively loaded four patients with 4 grams of L-tryptophan, and implanted DBS electrodes in the periaqueductal gray (PAG). Results: Upon loading the patients with 4 grams of L-tryptophan two weeks preoperatively and the continual use of tryptophan at doses greater than 2.5 grams, we note a significant improvement in the pain symptoms of all of our patients implanted at the PAG. Upon decrease in L-tryptophan dose below 2.5 grams, every patient experienced return of their pain symptoms despite PAG stimulation. The average length of followup is 9.75 months with a range of three to 14. Conclusions: Tryptophan loading of the patient prior to PAG electrode placement, and the continued use of tryptophan postoperatively correlates with better outcomes and more significant pain reduction. Tryptophan probably increases serotonin levels and results in activation of anti-nociceptive pain pathways at the PAG.

Strategies for treatment of gait and posture associated deficits in movement disorders: The impact of deep brain stimulation

Gait difficulties occur early in the course of Parkinson's disease (PD) as well as in generalized dystonia. Deep brain stimulation (DBS) is an effective treatment for patients with PD or dystonia. PD-associated slowness of gait improves dramatically after this procedure. Since not all gait problems can be treated with DBS, it is mandatory to assess the patient's symptoms precisely before an operation can be considered. In advanced stages of PD, postural deficits causing frequent falls are a major concern and will necessitate other strategies. In dystonia, walking may become possible only after this surgical intervention. After the implantation of DBS electrodes, rehabilitative treatment is necessary to (i) to establish new movement patterns, (ii) preserve an appropriate activity level, and (iii) treat specific disability, which resulted from secondary changes of the musculoskeletal system during pathological muscle tension in dystonia. An integrated multimodal approach, which has been adopted in our institution is presented.

Deep brain stimulation of the internal globus pallidus in dystonia: target localisation under general anaesthesia

Deep brain stimulation (DBS) of the internal globus pallidus (Gpi) is an effective therapy for various types of dystonia. The authors describe their technical approach for securing appropriate placement of the stimulating electrodes within the Gpi under general anaesthesia, including MRI based individualised anatomical targeting combined with electrophysiological mapping of the Gpi using micro-recording (MER) as well as macrostimulation and report the subsequent clinical outcome and complications using this method. We studied 42 patients (male-female ratio 25:17; mean age 43.6 years, range 9 to 74 years) consecutively operated at the Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, between 2001 - 2006. One patient underwent unilateral implantation after a right-sided pallidotomy 30 years before and strictly unilateral symptoms; all other implantations were bilateral. Two patients had repeat surgery after temporary removal of uni- or bilateral implants secondary to infection. Overall, 86 DBS electrodes were implanted. In 97% of the implantations, at least three microelectrodes were inserted simultaneously for MER and test stimulation. Initial anatomical targeting was based on stereotactic atlas coordinates and individual adaptation by direct visualisation of the Gpi on the stereotactic T2 or inversion-recovery MR images. The permanent electrode was placed according to the results of MER and test stimulations for adverse effects. The average improvement from baseline in clinical ratings using either the Burke-Fahn-Marsden-Dystonia (BFMDRS) or Toronto-Western-Spasmodic-Torticollis (TWSTR) rating scale at the last post-operative follow-up (mean 16.4 ; range 3-48 months) was 64.72% (range 20.39 to 98.52%). The post-operative MRI showed asymptomatic infarctions of the corpus caudatus in three patients and asymptomatic small haemorrhages in the lateral basal ganglia in two patients. One patient died due to a recurrent haemorrhage which occurred three months after the operation. The electrodes were implanted as follows: central trajectory in 64%, medial trajectory in 20%, anterior in 9% and lateral dorsal trajectories in 3.5% each. The reduction in BFMDRS or TWSTR motor score did not differ between the group implanted in the anatomically defined (central) trajectory bilateral (-64.15%, SD 23.8) and the physiologically adopted target (uni- or bilateral) (-63.39%, SD 23.1) indicating that in both groups equally effective positions were chosen within Gpi for chronic stimulation (t-test, p > 0.4). The described technique using stereotactic MRI for planning of the trajectory and direct visualisation of the target, intra-operative MER for delineating the boundaries of the target and macrostimulation for probing the distance to the internal capsule by identifying the threshold for stimulation induced tetanic contractions is effective in DBS electrode implantation in patients with dystonia operated under general anaesthesia. The central trajectory was chosen in only 64%, despite individual adaptation of the target due to direct visualisation of the Gpi in inversion recovery MRI in 43% of the patients, demonstrating the necessity of combining anatomical with neurophysiological information.

Direction and Predictive Factors for the Shift of Brain Structure During Deep Brain Stimulation Electrode Implantation for Advanced Parkinson’s Disease

Objectives. The aims of this study were to clarify the direction and degree of brain shift, and to determine the predictive factors for a brain shift during deep brain stimulation (DBS) of the subthalamic nucleus (STN). Materials and Methods. To evaluate the brain shift during bilateral STN-DBS, the position of the anterior commissure (AC), posterior commissure (PC), midcommissure point (MC), and tip of the frontal lobe and anterior horn of the lateral ventricle were calculated pre- and poststereotactic operations in the three-dimensional direction employing special software (Leksell SurgiPlan). To determine the predictive factors for a brain shift, patient's age, operation hours, width of the third ventricle, bicaudate index (BCI), and cella media index (CMI) were compared with the shift of MC. Results. In 50 patients, the MC shifted mainly in the posterior direction (y-axis: 1.27±0.7mm), and the shifts in the inferior direction (z-axis: 0.11±0.43mm) and lateral direction (x-axis: 0.02±0.39mm) were small. The shift of the MC in the posterior direction correlated well with the shift of the tip of the anterior lobe and anterior horn. Among the predictive factors examined, namely, the patient's age, operation hours, width of the third ventricle, BCI, and CMI, only the CMI showed a correlation with the shift of the MC (r=0.42, p<0.01, Pearson's correlation coefficient; and p<0.05, logistic regression analysis). Conclusions. In bilateral STN-DBS, brain shift occurred mainly in the posterior direction, and the CMI is useful for the prediction of a brain shift. Enlargement of the body part of the lateral ventricle is the most reliable factor for predicting a brain shift.

The influence of reactivity of the electrode–brain interface on the crossing electric current in therapeutic deep brain stimulation

The use of deep brain stimulation (DBS) as an effective clinical therapy for a number of neurological disorders has been greatly hindered by the lack of understanding of the mechanisms which underlie the observed clinical improvement in patients. This problem is confounded by the difficulty of investigating the neuronal effects of DBS in situ, and the impossibility of measuring the induced current in vivo. In our recent computational work using a quasi-static finite element (FEM) model we have quantitatively shown that the properties of the depth electrode–brain interface (EBI) have a significant effect on the electric field induced in the brain volume surrounding the DBS electrode. In the present work, we explore the influence of the reactivity of the EBI on the crossing electric current using the Fourier-FEM approach to allow the investigation of waveform attenuation in the time domain. Results showed that the EBI affected the waveform shaping differently at different post-implantation stages, and that this in turn had implications on induced current distribution across the EBI. Furthermore, we investigated whether hypothetical waveforms, which were shown to have potential usefulness for neural stimulation but are not yet applied clinically, would have any advantage over the currently used square pulse. In conclusion, the influence of reactivity of the EBI on the crossing stimulation current in therapeutic DBS is significant, and affects the predictive estimation of current distribution around the implanted DBS electrode in the human brain.

Outcome of Bilateral Subthalamic Nucleus Stimulation in the Treatment of Parkinson’s Disease: Correlation with Intra-Operative Multi-Unit Recordings but Not with the Type of Anaesthesia

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) gained general acceptance in the treatment of Parkinson’s disease (PD). Objective: To study the clinical outcome and the predicting factors of efficacy of chronic STN stimulation, while DBS electrodes were implanted under local or general anaesthesia with intra-operative electrophysiological guidance based on multi-unit recordings. Methods: We included a large single-centre cohort of 54 patients with advanced PD (mean age: 59 years; disease duration: 14 years). Clinical evaluation was performed by the Unified Parkinson’s Disease Rating Scale (UPDRS) before and 1 year after surgical placement of DBS electrodes. Results: In the on-stimulation and off-medication condition, the UPDRS part III score was reduced by 56% compared to the off-stimulation condition or pre-operative off-drug score. In the on-stimulation and on-medication condition, this score was reduced by 73%. The severity of motor fluctuations and dyskinesia (UPDRS part IV) and the activities of daily living (UPDRS part II) were reduced by 65 and 80%, respectively, in the on-stimulation/on-medication condition compared to the pre-operative baseline. The daily dose of antiparkinsonian treatment was diminished by 72%. Among the various pre- and intra-operative data, the most important predictive factor for clinical efficacy of STN stimulation was the length of hyperactivity along the best track observed in intra-operative multi-unit recordings. Other predictive factors included age, disease duration and pre-operative levodopa responsiveness or baseline off-drug values of the Hoehn and Yahr and UPDRS part III scores. In contrast, the type of anaesthesia (local vs. general) did not significantly influence the clinical outcome. Conclusion: The present results are in the average of previously published results, but they have been obtained from a large single-centre cohort of patients with important reductions in the daily dose of antiparkinsonian drugs. This study confirmed the efficacy of the STN-DBS technique and emphasized the value of an original intra-operative electrophysiological approach based on multi-unit and not single-unit quantified recordings. This method allows DBS electrode implantation to be safely performed under general anaesthesia without lessening the rate of efficacy of the procedure.

A biophysically inspired microelectrode recording-based model for the subthalamic nucleus activity in Parkinson's disease

The subthalamic nucleus (STN) plays a central role in movement actuation and manifestation of movement disorders (i.e., tremor, rigidity, akynesia and postural instability) in Parkinson's disease (PD) patients. Moreover, it has been recently revealed that an opportune electrical stimulation of the STN, called deep brain stimulation (DBS), can strongly contribute to the annihilation of the PD-related motor disorders. Currently, a great effort is made both in Medicine, Neurosciences and Engineering for understanding and modeling in details how the STN works, how PD determines its pathological behavior and DBS restores the correct motor function. The paper is organized in two parts. Firstly some stochastic properties of the STN electrical activity are obtained by analyzing a preliminary set of experimental data coming from microelectrode recordings (MERs) in two PD patients who underwent the surgical implantation of DBS electrodes. Then, a nonlinear, stochastic, continuous-state model describing the global electrical behavior of the STN in PD patients is proposed. It is inspired by the fundamental physiologic features of the subthalamic cells and a fictitious vector state is introduced to represent the main dynamics. Its numerical parameters and stochastic properties are chosen by fitting the available data.

Electrode Implantation for Deep Brain Stimulation in Dystonia: A Fast Spin-Echo Inversion-Recovery Sequence Technique for Direct Stereotactic Targeting of the Gpi

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment for medically refractory primary dystonia. We present our technique for direct preoperative visualization of the target using a fast spin-echo inversion-recovery (FSE-IR) sequence. Twenty-three consecutive patients (mean age 41 years, range 9-68 years, male to female ratio 11:12) with severe dystonia were operated using a combination of FSE-IR imaging for direct visualization of the globus pallidus internus with stereotactic, gadolinium-enhanced T1-MPRage images. The complete procedure, including stereotactic MRI, was performed under general anesthesia with propofol and remifentanyl. We used multichannel microdrive systems (Medtronic; Alpha-Omega) to introduce up to five parallel microelectrodes for microelectrode recordings (MER) and test stimulation with the central trajectory directed at the anatomically predefined target. The initial standard coordinates in relation to the mid-commissural point (mid-AC-PC) were as follows: lateral 21 mm, anterior 3 mm, and inferior 2 mm, which were then adapted to the individual case based on direct visualization of the target area and further refined by the intraoperative neurophysiology. In ten patients (43%) atlas-based standard coordinates were modified based on the direct visualization of the GPi in the FSE-IR images (bilaterally in seven patients, unilaterally in three). The modified targets ranged from 18.5 to 23.5 mm (mean 20.76 mm) laterally, 1-7 mm (mean 2.75 mm) anteriorly and 1-2 mm (mean 1.95 mm) inferiorly to the mid-AC-PC. We implanted the permanent electrode based on the results of MER and intraoperative stimulation performed to determine the threshold for pyramidal tract responses on the central trajectory in 67%, medially in 16%, anteriorly in 11%, laterally in 4%, dorsally in 2%. The procedure resulted in excellent clinical benefits (average reduction of the Burke-Fahn-Marsden Dystonia Rating Score (BFMDRS) or the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) were respectively 65.9%, range 20.9-91.4%) within the first year after surgery. Safety was demonstrated by the absence of intracranial bleeding or other surgical complications causing neurological morbidity. Inversion recovery sequences are an excellent tool for direct visualization of the GPi. These images can be fused to stereotactic MRI or CCT and may help to improve anatomical targeting of the GPi for the implantation of DBS electrodes.

Extracellular spike microrecordings from the subthalamic area in Parkinson’s disease

Intraoperative neuronal microrecordings can help in localizing the subthalamic nucleus (STN) during stereotactic neurosurgery for deep-brain stimulation (DBS) in Parkinson’s disease. To obtain quantitative information on neuronal spike descriptors, we systematically analysed neuronal spikes in the STN and substantia nigra pars reticulata (SNr) in 31 sides of the brain in awake patients undergoing stereotactic neurosurgery for DBS electrode implantation. In these two structures we evaluated spike amplitude, area, duration, rise time and mean total firing rate. The recording spike density was higher in the STN than in the SNr (94% vs. 28%). Microelectrode recordings showed a larger spike area and amplitude in the SNr than in the STN ([mean ± SD] amplitude: 46.7 ± 31.1 vs. 36.3 ± 29.6 μV; area: 25.6 ± 24.2 vs. 36.7 ± 21.4 μVmsec), a higher total firing rate at rest in the SNr than in the STN (78.6 ± 53.5 vs. 61.9 ± 40.8 Hz), and a longer duration and rise time in the SNr than in the STN (duration: 2.0 ± 1 vs. 1.3 ± 0.6 ms; rise time: 0.95 ± 0.6 vs. 0.67 ± 0.3 ms). Our analysis also revealed sex-related differences in the studied spike descriptors, paralleling recent findings from deep electroencephalography recordings. In the STN, males had larger spike area and amplitude (amplitude: 41.97 ± 32.57 vs. 26.2 ± 19.7 μV; area: 31.8 ± 26.4 vs. 13.0 ± 10.6 μVmsec), whereas females had higher mean total firing rate (66.7 ± 53.4 vs. 82.8 ± 50.8 Hz). Our results have implications for clinical practice and the development of algorithms for the neurophysiological identification of the STN during stereotactic neurosurgery for Parkinson’s disease, based on the on-line automated computation of multiple spike-variables.

Pedunculopontine nucleus microelectrode recordings in movement disorder patients

The pedunculopontine nucleus (PPN) lies within the brainstem reticular formation and is involved in the motor control of gait and posture. Interest has focused recently on the PPN as a target for implantation of chronic deep brain stimulation (DBS) electrodes for Parkinson's disease (PD) and progressive supranuclear palsy (PSP) therapy. The aim of this study was to examine the neurophysiology of the human PPN region and to identify neurophysiological landmarks that may aid the proper placement of DBS electrodes in the nucleus for the treatment of PD and PSP. Neuronal firing and local field potentials were recorded simultaneously from two independently driven microelectrodes during stereotactic neurosurgery for implantation of a unilateral DBS electrode in the PPN in five PD patients and two PSP patients. Within the PPN region, the majority (57%) of the neurons fired randomly while about 21% of the neurons exhibited 'bursty' firing. In addition, 21% of the neurons had a long action potential duration and significantly lower firing rate suggesting they were cholinergic neurons. A change in firing rate produced by passive and/or active contralateral limb movement was observed in 38% of the neurons that were tested in the PPN region. Interestingly, oscillatory local field potential activity in the beta frequency range ( approximately 25 Hz) was also observed in the PPN region. These electrophysiological characteristics of the PPN region provide further support for the proposed role of this region in motor control. It remains to be seen to what extent the physiological characteristics of the neurons and the stimulation-evoked effects will permit reliable identification of PPN and determination of the optimal target for DBS therapy.

Accuracy of stereotactic electrode placement in deep brain stimulation by intraoperative computed tomography

The purpose of this study was to evaluate the accuracy of stereotactic electrode placement in patients undergoing deep brain stimulation by using pre- and postoperative computed tomography (CT). Twenty-three patients with movement disorders (Parkinson's disease ( n = 7), tremor ( n = 9), dystonia ( n = 7)) treated with bilateral deep brain stimulation (DBS) (overall 46 target points) were investigated. The target point of the electrode was planned stereotactically in combination with a preoperative stereotactic helical computed tomography (CT). A postoperative CT, which was carried out still in the operating room while the patient had the stereotactic frame on the head, was performed in order to control the position of the electrodes in relation to the previously planned target point. The position of the four electrode contacts was measured according to the Talairach space (AC–PC line) and compared with the coordinates of the planned target point. The mean spatial distance of planned target perpendicular to the electrode was 1.32 ± 0.75 mm. These results show the high accuracy of stereotactic implantation of DBS electrodes assisted by pre- and postoperative image fusion with computed tomography (CT).

Characteristics and distribution of somatosensory evoked potentials in the subthalamic region

The aim of the present study is to evaluate the topographical distribution of somatosensory evoked potentials (SSEPs) in the subthalamic area, including the zona incerta (ZI). Determination of this distribution may help in the correct placement of deep brain stimulation (DBS) leads. Intraoperative SSEPs were recorded from contacts of DBS electrodes at 221 sites in 41 patients: three patients with essential tremor and 38 with Parkinson disease who underwent implantation of DBS electrodes for the relief of severe tremor or parkinsonism. Two distinct SSEPs were recorded in the subthalamic area. One was a monophasic positive wave with a mean latency of 15.8 +/- 0.9 msec, which the authors designated subthalamic P16. Using both cephalic and noncephalic references, subthalamic P16 was only recorded in the ventral part of the ZI (mean 6.6 +/- 1.3 mm posterior to the midcommissure point, 4.8 +/- 1.2 mm inferior to the anterior commissure-posterior commissure line, and 9.7 +/- 0.6 mm lateral to the midline). When bipolar recordings were made, the traces showed a phase reversal at the caudal part of the ZI. The second potential is a positive-negative SSEP recorded throughout the entire subthalamic area. The mean latencies of the initial positive peak and the major negative peak were 13.6 +/- 1.1 msec and 16.4 +/- 1.1 msec, respectively. Several small notches were superimposed on the peaks, and their amplitudes were largest at the contact close to the medial lemniscus. The results indicate that intraoperative SSEPs from DBS electrodes are helpful in refining stereotactic targets in the thalamus and subthalamic areas.

Bispectral Index Monitoring Does Not Improve Anesthesia Performance in Patients with Movement Disorders Undergoing Deep Brain Stimulating Electrode Implantation

Deep brain stimulation (DBS) has emerged as a promising therapy for movement disorders. During the implantation procedure for the electrodes, the patient emerges from anesthesia repeatedly to facilitate neurological testing. We investigated whether Bispectral Index (BIS) monitoring would be beneficial in patients receiving "sleep-awake-sleep" anesthesia with respect to time of arousal, consumption of propofol, and cardiopulmonary stability (i.e., heart rate, arterial blood pressure, and end-tidal carbon dioxide). We investigated 21 patients scheduled for implantation of DBS electrodes. Depth of propofol anesthesia was controlled either with BIS guidance in 10 patients (BIS group) or without in 11 patients (non-BIS group). In the BIS group, a BIS score of 40-60 was targeted during sleep periods, whereas in the non-BIS group, a value of 1 (= no response to tactile stimulation [unconsciousness]) on the Observers' Assessment of Alertness/Sedation Scale was targeted. For analgesia, the sites for the burr holes and for the pins of the stereotactic ring were infiltrated with 2% lidocaine; no opioids were used. For periods during which an awake patient required neurological testing, propofol was discontinued. We found no difference between groups with respect to times of arousal, total amount of propofol consumption, and cardiopulmonary stability. However, significantly more propofol boluses had to be administered in the BIS group (30 +/- 11.6 vs 17 +/- 4.6) to maintain the BIS score within the target range (P < 0.05). BIS monitoring does not improve anesthesia management for DBS electrode implantation in patients with movement disorders.

Neuronal Firing Rates and Patterns in the Globus Pallidus Internus of Patients With Cervical Dystonia Differ From Those With Parkinson's Disease

Cervical dystonia (CD) is a movement disorder that involves involuntary turning and twisting of the neck caused by abnormal muscle contraction. Deep brain stimulation (DBS) in the globus pallidus internus (GPi) is used to treat both CD and the motor symptoms of Parkinson's disease (PD). It has been suggested that the differing motor symptoms in CD and PD may arise from a decreased GPi output in CD and elevation of output in PD. To test this hypothesis, extracellular recordings of GPi neuronal activity were obtained during stereotactic surgery for the implantation of DBS electrodes in seven idiopathic CD and 14 PD patients. The mean GPi neuronal firing rate recorded from CD patients was lower than that in PD patients (P < 0.001; means +/- SE: 71.4 +/- 2.2 and 91.7 +/- 3.0 Hz, respectively). Furthermore, GPi neurons fired in a more irregular pattern consisting of more frequent and longer pauses in CD compared with PD patients. When comparisons were done based on locations of recordings, these differences in firing rates and patterns were limited to the ventral portion of the GPi. In contrast, no difference in firing rate or pattern was observed in the globus pallidus externus between the two groups. These findings suggest that alterations in both firing rate and firing pattern may underlie the differing motor symptoms associated with these two movement disorders.

Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease

Gait disturbances and akinesia are extremely disabling in advanced Parkinson's disease. It has been suggested that modulation of the activity of the pedunculopontine nucleus (PPN) may be beneficial in the treatment of these symptoms. We report the clinical affects of deep brain stimulation (DBS) in the PPN and subthalamic nucleus (STN). Six patients with unsatisfactory pharmacological control of axial signs such as gait and postural stability underwent bilateral implantation of DBS electrodes in the STN and PPN. Clinical effects were evaluated 2-6 months after surgery in the OFF- and ON-medication state, with both STN and PPN stimulation ON or OFF, or with only one target being stimulated. Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score, followed by a decline to give a final improvement of 32% in the score after 3-6 months. In contrast, bilateral STN-DBS at 130-185 Hz led to about 54% improvement. PPN-DBS was particularly effective on gait and postural items. In ON-medication state, the association of STN and PPN-DBS provided a significant further improvement when compared to the specific benefit mediated by the activation of either single target. Moreover, the combined DBS of both targets promoted a substantial amelioration in the performance of daily living activities. These findings indicate that, in patients with advanced Parkinson's disease, PPN-DBS associated with standard STN-DBS may be useful in improving gait and in optimizing the dopamine-mediated ON-state, particularly in those whose response to STN only DBS has deteriorated over time. This combination of targets may also prove useful in extra-pyramidal disorders, such as progressive supranuclear palsy, for which treatments are currently elusive.

Subthalamic nucleus deep brain stimulation in elderly patients – analysis of outcome and complications

BackgroundThere is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain.MethodsBilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age ≥ 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined.ResultsSignificant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups.ConclusionDBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate.

Successful deep brain stimulation of the globus pallidus internus in a patient with adult onset primary axial dystonia

Axial dystonia is a rare manifestation of adult onset primary segmental dystonia. Typically patients present with craniocervical dystonia spreading to the trunk but not to the extremities. Affected patients are disabled predominantly by flexion spasms of the trunk which are worsened on action especially during standing and walking. Response to drug therapy is often poor and local botulinum toxin injections are of limited value in these patients. Here we report a patient with axial dystonia who was successfully treated with deep brain stimulation (DBS) of the globus pallidus internus bilaterally (GPi). This 39 year old woman presented with a three year history of truncal spasms with predominant flexion and lateral bending of the trunk. Onset was subacute during her first pregnancy. There was gradual spread of dystonia from back muscles to both shoulders and also to the neck, although axial dystonia continued to be the most relevant problem. Three years into her disease action induced dystonia was so severe that she was hardly able to walk because her trunk was flexed by almost 90° and also severely bent to the left side whenever she attempted to walk. There was no dystonia in arms or legs apart from mild bilateral dystonic posturing (Fahn-Marsden Score: 21). Extensive laboratory investigations were unrevealing. No mutation in the DYT1 gene was found. Medical treatment with zolpidem, zopiclone and bromazepam did not improve her symptoms. In view of symptom severity we opted for bilateral implantation of DBS electrodes in the GPi given previous favourable reports of GPi stimulation in patients with primary generalised and focal dystonia. Post-operatively, symptoms improved within the first few days. There was further improvement over the following 3 months. Subjectively, the patient reported an improvement of 95%. Currently, she has mild torticollis, dystonic posturing of her left arm, mild dystonia involving the right shoulder and mild axial dystonia with marginal trunk bending to the left on action (Fahn-Marsden Score: 4). Gait and posture and the remainder of the neurological examination are otherwise normal.