Position-Dependent Dysfunction of Deep Brain Stimulation in Tourette Syndrome: Diagnostic Clues

Background: Detection of defective deep brain stimulation (DBS) contacts/electrodes is sometimes challenging. Case Report: We report a patient with Tourette syndrome (TS), who presented with abrupt tic increase and mild generalized headache 9 years after DBS implantation. On the suspicion of a hardware defect, a fracture of the DBS electrode and extension lead was ruled out by radiography and standard implantable pulse generator readouts. Further investigation revealed position-dependent modifiable therapeutic impedances, suggesting an impaired contact of the extension lead/adaptor. After replacement normal impedances were recorded, and the patient fully recovered. Discussion: In DBS dysfunction with inconspicuous hardware check, position-dependent defects might be suspected

Shape Abnormalities of the Caudate Nucleus Correlate with Poorer Gait and Balance: Results from a Subset of the LADIS Study

Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in fronto-striatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter changes (WMC) on MRI has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction

Does being physically active prevent future disability in older people? Attenuated effects when taking time-dependent confounders into account

Abstract Background Causal experimental evidence that physical activity prevents disability in older people is sparse. Being physically active has nonetheless been shown to be associated with disability-free survival in observational studies. Observational studies are, however, prone to bias introduced by time-dependent confounding. Time-dependent confounding occurs when an exposure (e.g. being physically active at some time-point) potentially affects the future status of a confounder (such as depression sometime later), and both variables have an effect on latter outcome (i.e. disability). “Conventional” analysis with e.g. Cox-regression is the mainstay when analyzing longitudinal observational studies. Unfortunately, it does not provide unbiased estimates in the presence of time-dependent confounding. Marginal structural models (MSM) – a relatively new class of causal models – have the potential to adequately account for time-dependent confounding. Here we analyze the effect of older people being physically active on disability, in a large long-term observational study. We address time-dependent confounding by using marginal structural models and provide a non-technical practical demonstration of how to implement this type of modeling. Methods Data is from 639 elderly individuals ascertained in the European multi-center Leukoaraiosis and Disability study (LADIS), followed-up yearly over a period of three years. We estimated the effect of self-reported physical activity on the probability to transit to instrumental disability in the presence of a large set of potential confounders. We compare the results of “conventional” modeling approaches to those estimated using marginal structural models, highlighting discrepancies. Results A “conventional” Cox-regression-like adjustment for salient baseline confounders signals a significant risk reduction under physical activity for later instrumental disability (OR 0.62, 95% CI 0.44–0.90). However, given MSM estimation, the effect is attenuated towards null (OR 1.00, 95% CI 0.57–1.76). Conclusions Contrary to most reports, we did not find that physical activity in older people prevents future instrumental disability, when taking time-dependent confounding into account. This result may be due to the characteristics our particular study population. It is, however, also conceivable that previous evidence neglected the effect of this type of bias. We suggest that analysts of longitudinal observational studies consider marginal structural models as a further modeling approach

Additional file 1: of Does being physically active prevent future disability in older people? Attenuated effects when taking time-dependent confounders into account

Supporting information. The Supporting information provides a non-technical introduction on how marginal structural models can be estimated generically. We provide a practical demonstration of how to implement this type of modeling using standard statistical software, discussing benefits and caveats. We include an additional figure that highlights the underpinnings of time-varying treatment, time-varying confounding and the inverse probability of treatment weight. The estimation steps presented in the main manuscript are cross-referenced in the Supporting information. (DOC 1488 kb

Development of Hyperkinesias after Long-term Pallidal Stimulation for Idiopathic Segmental Dystonia

Background:&nbsp;Chronic deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become an established treatment for dystonia. While bradykinetic symptoms may occur on chronic stimulation, the appearance of hyperkinetic movements has not been well characterized.Case Report:&nbsp;We report on the development of hyperkinesias after more than 10 years of GPi DBS.Discussion:&nbsp;Hyperkinesias may evolve upon long-term GPi DBS in dystonia. This might be related to a combined effect consisting of a reduced threshold for effective GPi stimulation for dystonia and spread of current to the globus pallidus externus.&nbsp;</p

Deep brain stimulation in patients on chronic antiplatelet or anticoagulation treatment

Background!#!In the aging society, many patients with movement disorders, pain syndromes, or psychiatric disorders who are candidates for deep brain stimulation (DBS) surgery suffer also from cardiovascular co-morbidities that require chronic antiplatelet or anticoagulation treatment. Because of a presumed increased risk of intracranial hemorrhage during or after surgery and limited knowledge about perioperative management, chronic antiplatelet or anticoagulation treatment often has been considered a relative contraindication for DBS. Here, we evaluate whether or not there is an increased risk for intracranial hemorrhage or thromboembolic complications in patients on chronic treatment (paused for surgery or bridged with subcutaneous heparin) as compared to those without.!##!Methods!#!Out of a series of 465 patients undergoing functional stereotactic neurosurgery, 34 patients were identified who were on chronic treatment before and after receiving DBS. In patients with antiplatelet treatment, medication was stopped in the perioperative period. In patients with vitamin K antagonists or novel oral anticoagulants (NOACs), heparin was used for bridging. All patients had postoperative stereotactic CT scans, and were followed up for 1 year after surgery.!##!Results!#!In patients on chronic antiplatelet or anticoagulation treatment, intracranial hemorrhage occurred in 2/34 (5.9%) DBS surgeries, whereas the rate of intracranial hemorrhage was 15/431 (3.5%) in those without, which was statistically not significant. Implantable pulse generator pocket hematomas were seen in 2/34 (5.9%) surgeries in patients on chronic treatment and in 4/426 (0.9%) without. There were only 2 instances of thromboembolic complications which both occurred in patients without chronic treatment. There were no hemorrhagic complications during follow-up for 1 year.!##!Conclusions!#!DBS surgery in patients on chronic antiplatelet or anticoagulation treatment is feasible. Also, there was no increased risk of hemorrhage in the first year of follow-up after DBS surgery. Appropriate patient selection and standardized perioperative management are necessary to reduce the risk of intracranial hemorrhage and thromboembolic complications

Centromedian–Parafascicular and Somatosensory Thalamic Deep Brain Stimulation for Treatment of Chronic Neuropathic Pain: A Contemporary Series of 40 Patients

Introduction: The treatment of neuropathic and central pain still remains a major challenge. Thalamic deep brain stimulation (DBS) involving various target structures is a therapeutic option which has received increased re-interest. Beneficial results have been reported in several more recent smaller studies, however, there is a lack of prospective studies on larger series providing long term outcomes. Methods: Forty patients with refractory neuropathic and central pain syndromes underwent stereotactic bifocal implantation of DBS electrodes in the centromedian–parafascicular (CM–Pf) and the ventroposterolateral (VPL) or ventroposteromedial (VPM) nucleus contralateral to the side of pain. Electrodes were externalized for test stimulation for several days. Outcome was assessed with five specific VAS pain scores (maximum, minimum, average pain, pain at presentation, allodynia). Results: The mean age at surgery was 53.5 years, and the mean duration of pain was 8.2 years. During test stimulation significant reductions of all five pain scores was achieved with either CM–Pf or VPL/VPM stimulation. Pacemakers were implanted in 33/40 patients for chronic stimulation for whom a mean follow-up of 62.8 months (range 3–180 months) was available. Of these, 18 patients had a follow-up beyond four years. Hardware related complications requiring secondary surgeries occurred in 11/33 patients. The VAS maximum pain score was improved by ≥50% in 8/18, and by ≥30% in 11/18 on long term follow-up beyond four years, and the VAS average pain score by ≥50% in 10/18, and by ≥30% in 16/18. On a group level, changes in pain scores remained statistically significant over time, however, there was no difference when comparing the efficacy of CM–Pf versus VPL/VPM stimulation. The best results were achieved in patients with facial pain, poststroke/central pain (except thalamic pain), or brachial plexus injury, while patients with thalamic lesions had the least benefit. Conclusion: Thalamic DBS is a useful treatment option in selected patients with severe and medically refractory pain

Sensory Alterations in Patients with Isolated Idiopathic Dystonia: An Exploratory Quantitative Sensory Testing Analysis

Abnormalities in the somatosensory system are increasingly being recognized in patients with dystonia. The aim of this study was to investigate whether sensory abnormalities are confined to the dystonic body segments or whether there is a wider involvement in patients with idiopathic dystonia. For this purpose, we recruited 20 patients, 8 had generalized, 5 had segmental dystonia with upper extremity involvement, and 7 had cervical dystonia. In total, there were 13 patients with upper extremity involvement. We used Quantitative Sensory Testing (QST) at the back of the hand in all patients and at the shoulder in patients with cervical dystonia. The main finding on the hand QST was impaired cold detection threshold (CDT), dynamic mechanical allodynia (DMA), and thermal sensory limen (TSL). The alterations were present on both hands, but more pronounced on the side more affected with dystonia. Patients with cervical dystonia showed a reduced CDT and hot detection threshold (HDT), enhanced TSL and DMA at the back of the hand, whereas the shoulder QST only revealed increased cold pain threshold and DMA. In summary, QST clearly shows distinct sensory abnormalities in patients with idiopathic dystonia, which may also manifest in body regions without evident dystonia. Further studies with larger groups of dystonia patients are needed to prove the consistency of these findings

Representation of Model Error in Convective-Scale Data Assimilation : Additive Noise, Relaxation Methods, and Combinations

For ensemble data assimilation, background error covariance should account for sampling and model errors. There are a number of approaches that have been developed that try to consider these errors;among them, additive noise and relaxation methods (relaxation to prior perturbation and relaxation to prior spread) are often used. In this work, we compare additive noise, based on random samples from global climatological atmospheric background error covariance, to relaxation methods as well as combinations. Our experiments have been conducted in framework of convective-scale data assimilation with conventional and radar reflectivity observations hourly assimilated for a 2-week convective period over Germany. In the first week under weather conditions characterized by strong large-scale forcing of convection, additive noise performs equally or even better than relaxation methods and combinations during both assimilation and short-range forecasts. In addition, it is shown that the relaxation to prior perturbation may be associated with smoothing of background errors that negatively affect small-scale structures and that the relaxation to prior spread yields more unbalanced model states. For the second week in absence of strong forcing, the performance of additive noise relative to combinations has been degraded a bit but results are still comparable. Overall, additive noise provides a good benchmark for further developments in representation of model error for convective-scale data assimilation