Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

BACKGROUND: Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. METHODS: All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. RESULTS: Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. CONCLUSIONS: GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.

The role of the motor thalamus in deep brain stimulation for essential tremor.

The advent of next-generation technology has significantly advanced the implementation and delivery of Deep Brain Stimulation (DBS) for Essential Tremor (ET), yet controversies persist regarding optimal targets and networks responsible for tremor genesis and suppression. This review consolidates key insights from anatomy, neurology, electrophysiology, and radiology to summarize the current state-of-the-art in DBS for ET. We explore the role of the thalamus in motor function and describe how differences in parcellations and nomenclature have shaped our understanding of the neuroanatomical substrates associated with optimal outcomes. Subsequently, we discuss how seminal studies have propagated the ventral intermediate nucleus (Vim)-centric view of DBS effects and shaped the ongoing debate over thalamic DBS versus stimulation in the posterior subthalamic area (PSA) in ET. We then describe probabilistic- and network-mapping studies instrumental in identifying the local and network substrates subserving tremor control, which suggest that the PSA is the optimal DBS target for tremor suppression in ET. Taken together, DBS offers promising outcomes for ET, with the PSA emerging as a better target for suppression of tremor symptoms. While advanced imaging techniques have substantially improved the identification of anatomical targets within this region, uncertainties persist regarding the distinct anatomical substrates involved in optimal tremor control. Inconsistent subdivisions and nomenclature of motor areas and other subdivisions in the thalamus further obfuscate the interpretation of stimulation results. While loss of benefit and habituation to DBS remain challenging in some patients, refined DBS techniques and closed-loop paradigms may eventually overcome these limitations.

The Challenge of Choosing the Right Stimulation Target for Dystonic Tremor-A Series of Instructive Cases.

Background: Thalamic deep brain stimulation (DBS) is established for medically refractory tremor syndromes and globus pallidus stimulation (GPi-DBS) for medically refractory dystonia syndromes. For combined tremor and dystonia syndromes, the best target is unclear. Objectives: We present four patients with two different profiles whose clinical course demonstrates that our current analysis of clinical symptomatology is not a sufficient predictor of surgical success. Methods: Outcome parameters were assessed with observer-blinded video ratings and included the Fahn-Tolosa-Marin-Tremor Rating Scale (FTM-TRS) and the Unified Dystonia Rating Scale (UDRS). Results: Two patients with "predominant lateralized action tremor" of the hands and mild cervical dystonia showed no relevant tremor improvement after GPi-DBS, but UDRS improved (mean, 45%). Rescue ventral intermediate nucleus of the thalamus (Vim)-DBS electrodes were implanted and both patients benefited significantly with a mean tremor reduction of 51%.Two other patients with "axial-predominant action tremor of the trunk and head" associated with cervical dystonia underwent bilateral Vim-DBS implantation with little effect on tremor (24% reduction in mean FTM-TRS total score) and no effect on dystonic symptoms. GPi rescue DBS was implanted and showed a significant effect on tremor (63% reduction in mean FTM-TRS) and dystonia (49% reduction in UDRS). Conclusions: The diagnosis of dystonic tremor alone is not a sufficient predictor to establish the differential indication of GPi- or Vim-DBS. Further criteria (eg, proximal-distal distribution of tremor/dystonia) are needed to avoid rescue surgery in the future. On the other hand, the course of our patients encourages rescue surgery in such severely disabled patients if the first target fails.

The Role of Levodopa Challenge in Predicting the Outcome of Subthalamic Deep Brain Stimulation.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective and evidence-based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN-DBS. Objective: The predictive validity of the levodopa challenge for individual patients is analyzed. Methods: Data from patients assessed with a preoperative Levodopa-test and a follow-up examination (mean ± standard deviation: 9.15 months ±3.39) from Kiel (n = 253), Berlin (n = 78) and Toronto (n = 98) were studied. Insufficient DBS outcome was defined as an overall UPDRS-III reduction <33% compared to UPDRS-III in med-off at baseline or alternatively if the minimal clinically important improvement of 5 points was not reached. Single UPDRS-items and sub-scores were dichotomized. Following exploratory analysis, we trained supervised regression- and classification models for outcome prediction. Results: Data analysis confirmed significant correlation between the absolute UPDRS-III reduction during Levodopa challenge and after stimulation. But individual improvement was inaccurately predicted with a large range of up to 30 UPDRS III points. Further analysis identified preoperative UPDRS-III/med-off-scores and preoperative Levodopa-improvement as most influential factors. The models for UPDRS-III and sub-scores improvement achieved comparably low accuracy. Conclusions: With large prediction intervals, the Levodopa challenge use for patient counseling is limited, though remains important for excluding non-responders to Levodopa. Despite these deficiencies, the current practice of patient selection is highly successful and builds not only on the Levodopa challenge. However, more specific motor tasks and further paraclinical tools for prediction need to be developed.

Intravenous thrombolysis and mechanical recanalization for acute ischemic stroke in deep brain stimulation patients: a case series.

BACKGROUND: Intravenous thrombolysis (IVT) and endovascular mechanical thrombectomy therapy (MT) are well established in the treatment of acute ischemic stroke. It is currently unclear whether these treatments can be applied in patients with previous deep brain stimulation (DBS) surgery and how long the interval to the DBS operation should be. METHODS: Four patients with ischemic stroke and IVT or MT were included in this retrospective case series. Data on demographics, genesis, severity and course of the stroke and the DBS indication were extracted and evaluated. Furthermore, a literature review was conducted. Outcomes and hemorrhagic complications after IVT, MT or intra-arterial thrombolysis in patients with prior deep brain stimulation surgery and intracranial surgery were analyzed. RESULTS: Four patients with acute ischaemic stroke and previous DBS surgery were treated with IVT (2 patients), MT (1) or a combined therapy of IVT and MT (1). The time interval to the previous DBS surgery was between 6 and 135 months. In these four patients, no bleeding complications occurred. The literature review revealed four publications with a total of 18 patients, who were treated with IVT, MT or intra-arterial thrombolysis. Of these 18 patients, only 1 had undergone deep brain stimulation surgery, the other 17 patients had received brain surgery for other reasons. Bleeding complications occurred in four of the 18 reported patients, but not in the DBS case. All four patients with bleeding complications were reported to have died as a result. In three of the four patients with fatal outcome, surgery was less than 90 days before the onset of stroke. CONCLUSION: IVT and MT were tolerated by four patients with ischemic stroke more than 6 months after DBS surgery without bleeding complications.

Long-term efficacy with deep brain stimulation of the globus pallidus internus in cervical dystonia: a retrospective monocentric study.

BACKGROUND: Cervical dystonia (CD) is characterized by involuntary contractions of the cervical muscles. Data on long-term effectiveness of deep brain stimulation (DBS) are rare. The aim of this study was to evaluate the longitudinal ten years treatment efficacy of DBS in the globus pallidus internus (GPI). METHODS: A retrospective single-center data analysis was performed on patients with idiopathic CD, who were treated with GPI DBS for at least 10 years. TWSTR severity score and individual sub-items were compared between pre and post DBS surgery (n = 15) over time. RESULTS: There was a significant and persistent positive effect regarding the severity of TWSTRS between the conditions immediately before and 1, 5, and 10 years after establishment of GPI DBS (mean difference: 6.6-7 ± 1.6). Patients with increasing CD complexity showed a poorer response to established treatment forms, such as injection of botulinum toxin and were thus DBS candidates. Especially a predominant torticollis was significantly improved by DBS. CONCLUSION: GPI DBS is an effective procedure especially in severely affected patients with a positive 10-year outcome. It should be considered in more complex CD-forms or predominant torticollis.

Genetic stratification of motor and QoL outcomes in Parkinson's disease in the EARLYSTIM study.

PURPOSE: The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. OBJECTIVE: First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. METHODS: We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. RESULTS: The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. CONCLUSIONS: Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.

Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia.

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and potential network effects have not been carried out. Here, we retrospectively studied clinical results following DBS for cervical and generalized dystonia in a multicenter cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce an approach to map optimal stimulation sites to anatomical space. Second, we investigate which tracts account for optimal clinical improvements, when modulated. Third, we investigate distributed stimulation effects on a whole-brain functional connectome level. Our results show marked differences of optimal stimulation sites that map to the somatotopic structure of the internal pallidum. While modulation of the striatopallidofugal axis of the basal ganglia accounted for optimal treatment of cervical dystonia, modulation of pallidothalamic bundles did so in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in the form of connectivity to the cerebellum and somatomotor cortex. Our results suggest a brief divergence of optimal stimulation networks for cervical vs. generalized dystonia within the pallidothalamic loop that merge again on a thalamo-cortical level and share a common whole-brain network.

The Contribution of Subthalamic Nucleus Deep Brain Stimulation to the Improvement in Motor Functions and Quality of Life.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. OBJECTIVES: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study. METHODS: Sixty-nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. RESULTS: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ-39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = -13.1, z = -6.3) and the PDQ-39 differed (x = 14.8, y = -12.4, z = -4.3) ~3.8 mm. CONCLUSIONS: The main influence of DBS on QoL is likely mediated through the sensory-motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

MaDoPO: Magnetic Detection of Positions and Orientations of Segmented Deep Brain Stimulation Electrodes: A Radiation-Free Method Based on Magnetoencephalography.

BACKGROUND: Current approaches to detect the positions and orientations of directional deep brain stimulation (DBS) electrodes rely on radiative imaging data. In this study, we aim to present an improved version of a radiation-free method for magnetic detection of the position and the orientation (MaDoPO) of directional electrodes based on a series of magnetoencephalography (MEG) measurements and a possible future solution for optimized results using emerging on-scalp MEG systems. METHODS: A directional DBS system was positioned into a realistic head-torso phantom and placed in the MEG scanner. A total of 24 measurements of 180 s each were performed with different predefined electrode configurations. Finite element modeling and model fitting were used to determine the position and orientation of the electrode in the phantom. Related measurements were fitted simultaneously, constraining solutions to the a priori known geometry of the electrode. Results were compared with the results of the high-quality CT imaging of the phantom. RESULTS: The accuracy in electrode localization and orientation detection depended on the number of combined measurements. The localization error was minimized to 2.02 mm by considering six measurements with different non-directional bipolar electrode configurations. Another six measurements with directional bipolar stimulations minimized the orientation error to 4°. These values are mainly limited due to the spatial resolution of the MEG. Moreover, accuracies were investigated as a function of measurement time, number of sensors, and measurement direction of the sensors in order to define an optimized MEG device for this application. CONCLUSION: Although MEG introduces inaccuracies in the detection of the position and orientation of the electrode, these can be accepted when evaluating the benefits of a radiation-free method. Inaccuracies can be further reduced by the use of on-scalp MEG sensor arrays, which may find their way into clinics in the foreseeable future.

Influence of Simulated Deep Brain Stimulation on the Expression of Inflammatory Mediators by Human Central Nervous System Cells In Vitro.

Deep brain stimulation (DBS) seems to modulate inflammatory processes. Whether this modulation leads to an induction or suppression of inflammatory mediators is still controversially discussed. Most studies of the influence of electrical stimulation on inflammation were conducted in rodent models with direct current stimulation and/or long impulses, both of which differ from the pattern in DBS. This makes comparisons with the clinical condition difficult. We established an in-vitro model that simulated clinical stimulation patterns to investigate the influence of electrical stimulation on proliferation and survival of human astroglial cells, microglia, and differentiated neurons. We also examined its influence on the expression of the inflammatory mediators C-X-C motif chemokine (CXCL)12, CXCL16, CC-chemokin-ligand-2 (CCL)2, CCL20, and interleukin (IL)-1ß and IL-6 by these cells using quantitative polymerase chain reaction. In addition, protein expression was assessed by immunofluorescence double staining. In our model, electrical stimulation did not affect proliferation or survival of the examined cell lines. There was a significant upregulation of CXCL12 in the astrocyte cell line SVGA, and of IL-1ß in differentiated SH-SY5Y neuronal cells at both messenger RNA and protein levels. Our model allowed a valid examination of chemokines and cytokines associated with inflammation in human brain cells. With it, we detected the induction of inflammatory mediators by electrical stimulation in astrocytes and neurons.

Determining the rotational orientation of directional deep brain stimulation electrodes using magnetoencephalography.

Objective.The aim of the present study was to evaluate the effect of different electrode configurations on the accuracy of determining the rotational orientation of the directional deep brain stimulation (DBS) electrode with our previously published magnetoencephalography (MEG)-based method.Approach.A directional DBS electrode, along with its implantable pulse generator, was integrated into a head phantom and placed within the MEG sensor array. Predefined bipolar electrode configurations, based on activation of different directional and omnidirectional contacts of the electrode, were set to generate a defined magnetic field during stimulation. This magnetic field was then measured with MEG. Finite element modeling and model fitting approach were used to calculate electrode orientation.Main results.The accuracy of electrode orientation detection depended on the electrode configuration: the vertical configuration (activation of two directional contacts arranged one above the other) achieved an average accuracy of only about 41 ∘. The diagonal configuration (activation of the electrode tip and a single directional contact at the next higher level of the electrode) achieved an accuracy of 13∘, while the horizontal electrode configuration (activation of two adjacent directional contacts at the same electrode level) achieved the best accuracy of 6∘. The accuracy of orientation detection of the DBS electrode depends on the change in spatial distribution of the magnetic field with the rotation of the electrode along its own axis. In the vertical configuration, rotation of the electrode has a small effect on the magnetic field distribution, while in the diagonal or horizontal configuration, electrode rotation has a significant effect on the magnetic field distribution.Significance.Our work suggests that in order to determine rotational orientation of a DBS electrode using MEG, horizontal configuration should be used as it provides the most accurate results compared to other possible configurations.

Investigation of Magnetoelectric Sensor Requirements for Deep Brain Stimulation Electrode Localization and Rotational Orientation Detection.

Correct position and orientation of a directional deep brain stimulation (DBS) electrode in the patient's brain must be known to fully exploit its benefit in guiding stimulation programming. Magnetoelectric (ME) sensors can play a critical role here. The aim of this study was to determine the minimum required limit of detection (LOD) of a ME sensor that can be used for this application by measuring the magnetic field induced by DBS. For this experiment, a commercial DBS system was integrated into a head phantom and placed inside of a state-of-the-art Superconducting Quantum Interference Device (SQUID)-based magnetoencephalography system. Measurements were performed and analyzed with digital signal processing. Investigations have shown that the minimum required detection limit depends on various factors such as: measurement distance to electrode, bandwidth of magnetic sensor, stimulation amplitude, stimulation pulse width, and measurement duration. For a sensor that detects only a single DBS frequency (stimulation frequency or its harmonics), a LOD of at least 0.04 pT/Hz0.5 is required for 3 mA stimulation amplitude and 60 µµs pulse width. This LOD value increases by an order of magnitude to 0.4 pT/Hz0.5 for a 1 kHz, and by approximately two orders to 3 pT/Hz0.5 for a 10 kHz sensor bandwidth. By averaging, the LOD can be reduced by at least another 2 orders of magnitude with a measurement duration of a few minutes.

Can Deep Brain Stimulation Withdrawal Syndromes Be Avoided by Removing Infected Implanted Pulse Generator and Cables with Contralateral Replacement in the Same Session?

OBJECTIVE: Infections are feared complications following deep brain stimulation in 1.9 to 17.6% of cases. These infections can necessitate the removal of implants, which carries the risk of life-threatening withdrawal syndromes, especially in patients suffering from Parkinson's disease. In this report, we describe our procedure of removing an infected implanted pulse generator (IPG) and cables with contralateral replacement in the same session. METHODS: We retrospectively analysed all patients with transpositions of an IPG and cables between 2017 and 2020 in a single-centre, university hospital setting. Medical records of all patients undergoing this particular surgical procedure were systematically reviewed. The shortest follow-up time was 12 months. RESULTS: Between 2017 and 2020, we had 6 patients with a high risk of withdrawal syndrome in whom an infected IPG with cables was removed and replaced on the opposite side in the same session. There were postoperative complications in 2 patients: in one, the generator had to be re-affixed, and in the second, a skin transplant was required over one electrode because of skin necrosis. No case of invasive infection was seen, and the stimulation therapy was not interrupted. CONCLUSION: One-session removal of an IPG and cables with contralateral replacement seems to be an effective therapy for patients at high risk of withdrawal syndrome.

Clinical patterns of gait freezing in Parkinson's disease and their response to interventions: An observer-blinded study.

BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD) is provoked by specific situations. The sensitivity of these situations to detect FOG and the relative FOG response to l-dopa and subthalamic nucleus deep brain stimulation (STN-DBS) is unknown. METHODS: Two blinded reviewers analyzed the video recordings of a standardized patient assessment before and 10 months after DBS-implantation of 124 PD patients with positive FOG according to the Unified Parkinson Rating Scale part II item 14. Baseline evaluations were done under 2 conditions (OFF- and ON-drug states). Postoperatively, the patients were evaluated under 4 conditions (OFF-drug/OFF-stim, OFF-drug/ON-stim, ON-drug/OFF-stim, and ON-drug/ON-stim). FOG frequency and its severity was rated during different provoking situations (start, turning, reaching a destination and open space hesitations) during a standardized walking task. Cumulative link mixed models were calculated to investigate the immediate and carry-over effect of medication and stimulation. RESULTS: Eighty-one percent of patients presented FOG at least in one provoking situation on video assessment. During turning, the FOG severity was significantly worse than for the other subtypes (p < 0.0001). Both interventions improve all FOG subtypes similarly. The effect size of l-dopa and STN-DBS on subtypes were similar (p > 0.05), but the combined intervention had a stronger effect on FOG severity (p < 0.0001) compared to each intervention separately. FOG severity was lower at follow-up OFF compared to baseline OFF condition (p < 0.02) demonstrating a carry-over effect of STN-DBS. CONCLUSION: Turning is the most sensitive provoking situation for gait freezing. STN-DBS and l-dopa improve all FOG subtypes similarly, their effect is stronger in combination.

Screening for Platelet Dysfunction and Use of Prophylactic Tranexamic Acid in Patients Undergoing Deep Brain Stimulation: A Retrospective Analysis of Incidence and Outcome of Intracranial Hemorrhage.

INTRODUCTION: The rate of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) is between 1.5 and 6.1%, with prolonged deficits occurring in 0.4-2.5% of the patients. This retrospective study investigates whether the prophylactic administration of tranexamic acid (TA) to patients with abnormal platelet function detected preoperatively by platelet function analyzer (PFA) lowered the risk for an ICH event. METHODS: We performed a systematic review of the medical records of 485 consecutively admitted patients who underwent bilateral DBS surgery in a single-center university hospital setting between 2009 and 2018. The cohort was split into two groups. In one group, preoperative PFA screening was performed (n = 156, patients recruited from 2014 to 2018), and TA was administered if platelet function was abnormal. No preoperative PFA was performed in the second group (n = 359, patients recruited from 2009 to 2013). Both cohorts were analyzed for the occurrence of ICH, defined by (i) detection of ICH in routine postoperative magnetic resonance/computed tomography imaging or (ii) in non-routine imaging for the onset of new neurological symptoms. RESULTS: Fourteen of the 156 screened patients (9%) showed reproducible PFA-100 closure abnormalities (3 with von Willebrand disease, 11 with no identifiable cause of platelet dysfunction). Two of the 156 patients (1.3%) in this cohort revealed an ICH on imaging, 1 of whom (0.6%) exhibited a prolonged neurological deficit as a result of ICH. In the cohort without platelet testing, 11 of the 329 patients (3.3%) demonstrated ICH on imaging, of whom 5 (1.5%) suffered from a prolonged neurological deficit. CONCLUSION: In this retrospective study, the screening and the administration of TA appeared to lower the risk of an ICH by 1.8%. One patient with von Willebrand disease suffered an ICH despite TA treatment. A prospective study is needed to clarify the impact of platelet testing and TA administration on the of incidence ICH.

A multicenter, open-label, controlled trial on acceptance, convenience, and complications of rechargeable internal pulse generators for deep brain stimulation: the Multi Recharge Trial.

OBJECTIVE: Rechargeable neurostimulators for deep brain stimulation have been available since 2008, promising longer battery life and fewer replacement surgeries compared to non-rechargeable systems. Long-term data on how recharging affects movement disorder patients are sparse. This is the first multicenter, patient-focused, industry-independent study on rechargeable neurostimulators. METHODS: Four neurosurgical centers sent a questionnaire to all adult movement disorder patients with a rechargeable neurostimulator implanted at the time of the trial. The primary endpoint was the convenience of the recharging process rated on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints were charge burden (time spent per week on recharging), user confidence, and complication rates. Endpoints were compared for several subgroups. RESULTS: Datasets of 195 movement disorder patients (66.1% of sent questionnaires) with Parkinson's disease (PD), tremor, or dystonia were returned and included in the analysis. Patients had a mean age of 61.3 years and the device was implanted for a mean of 40.3 months. The overall convenience of recharging was rated as "easy" (4). The mean charge burden was 122 min/wk and showed a positive correlation with duration of therapy; 93.8% of users felt confident recharging the device. The rate of surgical revisions was 4.1%, and the infection rate was 2.1%. Failed recharges occurred in 8.7% of patients, and 3.6% of patients experienced an interruption of therapy because of a failed recharge. Convenience ratings by PD patients were significantly worse than ratings by dystonia patients. Caregivers recharged the device for the patient in 12.3% of cases. Patients who switched from a non-rechargeable to a rechargeable neurostimulator found recharging to be significantly less convenient at a higher charge burden than did patients whose primary implant was rechargeable. Age did not have a significant impact on any endpoint. CONCLUSIONS: Overall, patients with movement disorders rated recharging as easy, with low complication rates and acceptable charge burden.

Microdialysis in postoperative monitoring of microvascular free flaps: Experiences with a decision algorithm.

BACKGROUND: Reconstruction with free flaps has become a usual practice in maxillofacial surgery. Clinical monitoring is still the standard approach for postoperative follow-up, but can be difficult or impossible with intraorally situated or buried flaps. Microdialysis is a sampling technique that offers the possibility to monitor the metabolism of flaps continuously. It is a reliable method for early diagnosis of ischemia. MATERIALS AND METHODS: 48 microvascular free flaps applied following oral cancer resection were monitored with a microdialysis (MD) catheter, placed in the flap. Glucose, lactate, and lactate/pyruvate ratio were monitored using a bedside analyser for 5 days. 48 free flaps served as controls and were assessed (refill, flap temperature, and color) by clinical monitoring (CM). RESULTS: 12 flaps monitored by MD showed abnormal metabolism and underwent revision. Eight flaps were saved and four were lost within the first 5 days postoperatively. In addition, two flaps were lost at days 15 and 30 postoperatively, without previous complications. Four flaps assessed by CM developed complications, underwent revision, and were saved. In addition, five flaps were lost between the 8th and 23rd days postoperatively, without revision, due to missing previous clinical signs. CONCLUSION: Postoperative monitoring of free flaps using a microdialysis decision algorithm allows early diagnosis of anastomotic complications. It is a clinically feasible and sensitive monitoring method for microvascular flaps, allowing surgical revision to be undertaken before clinical alteration takes place.

Do Adaptors Shorten the Battery Life of Nonrechargeable Generators for Deep Brain Stimulation?

OBJECTIVE: Generators implanted for deep brain stimulation must be replaced after several years. If a Kinetra generator is replaced by the Activa-PC, an adaptor will be required to attach it to the original extension cables. On the basis of our clinical impression that the battery life of the Active-PC generator was shorter when an adaptor was used, we performed this retrospective study. METHODS: We determined the battery lifetimes of deep brain stimulation generators that had been implanted in our department. The inclusion criterion was the initial implantation of a Kinetra generator that was later replaced by an Activa-PC with adaptor, which itself was subsequently also replaced. These patients were compared with an Activa-PC control group without an adaptor but identical with regard to number of battery exchanges, disease, and target. RESULTS: There were 28 patients in the study group and 14 in the control group. Battery lifetime of the Activa-PC with adaptor (32.4 ± 7.7 months) was significantly shorter than that of the Kinetra (53.5 ± 15.7 months, P = 0.000006). The battery life of Activa-PC without an adaptor (35.3 ± 8.2 months) did not differ significantly from that of the Activa-PC with an adaptor (P = 0.333). CONCLUSIONS: The battery lifetime in a replacement Activa-PC is shorter than that in the original Kinetra generator. Adaptors have no significant effect on battery life. Patients should be informed that the battery in their new generator must be checked more frequently than before.

Probabilistic mapping of the antidystonic effect of pallidal neurostimulation: a multicentre imaging study.

Deep brain stimulation of the internal globus pallidus is a highly effective and established therapy for primary generalized and cervical dystonia, but therapeutic success is compromised by a non-responder rate of up to 25%, even in carefully-selected groups. Variability in electrode placement and inappropriate stimulation settings may account for a large proportion of this outcome variability. Here, we present probabilistic mapping data on a large cohort of patients collected from several European centres to resolve the optimal stimulation volume within the pallidal region. A total of 105 dystonia patients with pallidal deep brain stimulation were enrolled and 87 datasets (43 with cervical dystonia and 44 with generalized dystonia) were included into the subsequent 'normative brain' analysis. The average improvement of dystonia motor score was 50.5 ± 30.9% in cervical and 58.2 ± 48.8% in generalized dystonia, while 19.5% of patients did not respond to treatment (<25% benefit). We defined probabilistic maps of anti-dystonic effects by aggregating individual electrode locations and volumes of tissue activated (VTA) in normative atlas space and ranking voxel-wise for outcome distribution. We found a significant relation between motor outcome and the stimulation volume, but not the electrode location per se. The highest probability of stimulation induced motor benefit was found in a small volume covering the ventroposterior globus pallidus internus and adjacent subpallidal white matter. We then used the aggregated VTA-based outcome maps to rate patient individual VTAs and trained a linear regression model to predict individual outcomes. The prediction model showed robustness between the predicted and observed clinical improvement, with an r2 of 0.294 (P < 0.0001). The predictions deviated on average by 16.9 ± 11.6 % from observed dystonia improvements. For example, if a patient improved by 65%, the model would predict an improvement between 49% and 81%. Results were validated in an independent cohort of 10 dystonia patients, where prediction and observed benefit had a correlation of r2 = 0.52 (P = 0.02) and a mean prediction error of 10.3% (±8.9). These results emphasize the potential of probabilistic outcome brain mapping in refining the optimal therapeutic volume for pallidal neurostimulation and advancing computer-assisted planning and programming of deep brain stimulation.