The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis.

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management. OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

[Pacemaker, organ or walking stick? Pre-op association with and post-op subjective perception of a deep brain stimulation device]. / Herzschrittmacher, Organ oder Gehstock? Vorher-Nachher-Befragung zur subjektiven Wahrnehmung eines Gerätes zur Tiefen Hirnstimulation.

AIM OF THE STUDY: This study was conducted in a pre-post design with a survey of patients who had undergone deep brain stimulation (DBS) as treatment for a neurological movement disorder. The aim of the study was to compare patients' expectations and beliefs before a DBS intervention with patients' subjective experience of this intervention. METHODOLOGY: The longitudinal study of patients (n=132) with an indication for DBS therapy was based on a written survey at the time points of preoperative screening (pre-op) and one-year follow-up (post-op). RESULTS: Preoperatively, a clear majority of respondents believed DSB to be similar to a pacemaker intervention, but one year after the intervention less than one third did so, as they compared DBS to using a walking stick or glasses. CONCLUSION: The experience of DBS in the patient's own body seems to be comparable by means of individually different associations, whereby the comparison with non-invasive aids predominates postoperatively. The discussion of these descriptions in the educational interview can contribute to a realistic horizon of patients' expectations before DBS.

Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

Invasive neurophysiology and whole brain connectomics for neural decoding in patients with brain implants.

Brain computer interfaces (BCI) provide unprecedented spatiotemporal precision that will enable significant expansion in how numerous brain disorders are treated. Decoding dynamic patient states from brain signals with machine learning is required to leverage this precision, but a standardized framework for identifying and advancing novel clinical BCI approaches does not exist. Here, we developed a platform that integrates brain signal decoding with connectomics and demonstrate its utility across 123 hours of invasively recorded brain data from 73 neurosurgical patients treated for movement disorders, depression and epilepsy. First, we introduce connectomics-informed movement decoders that generalize across cohorts with Parkinson's disease and epilepsy from the US, Europe and China. Next, we reveal network targets for emotion decoding in left prefrontal and cingulate circuits in DBS patients with major depression. Finally, we showcase opportunities to improve seizure detection in responsive neurostimulation for epilepsy. Our platform provides rapid, high-accuracy decoding for precision medicine approaches that can dynamically adapt neuromodulation therapies in response to the individual needs of patients.

Local Field Potentials Predict Motor Performance in Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment option for patients with Parkinson's disease (PD). However, clinical programming remains challenging with segmented electrodes. OBJECTIVE: Using novel sensing-enabled neurostimulators, we investigated local field potentials (LFPs) and their modulation by DBS to assess whether electrophysiological biomarkers may facilitate clinical programming in chronically implanted patients. METHODS: Sixteen patients (31 hemispheres) with PD implanted with segmented electrodes in the subthalamic nucleus and a sensing-enabled neurostimulator were included in this study. Recordings were conducted 3 months after DBS surgery following overnight withdrawal of dopaminergic medication. LFPs were acquired while stimulation was turned OFF and during a monopolar review of both directional and ring contacts. Directional beta power and stimulation-induced beta power suppression were computed. Motor performance, as assessed by a pronation-supination task, clinical programming and electrode placement were correlated to directional beta power and stimulation-induced beta power suppression. RESULTS: Better motor performance was associated with stronger beta power suppression at higher stimulation amplitudes. Across directional contacts, differences in directional beta power and the extent of stimulation-induced beta power suppression predicted motor performance. However, within individual hemispheres, beta power suppression was superior to directional beta power in selecting the contact with the best motor performance. Contacts clinically activated for chronic stimulation were associated with stronger beta power suppression than non-activated contacts. CONCLUSIONS: Our results suggest that stimulation-induced ß power suppression is superior to directional ß power in selecting the clinically most effective contact. In sum, electrophysiological biomarkers may guide programming of directional DBS systems in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Multidisciplinary Approach to Sedation and Early Mobility of Intubated Critically Ill Neurologic Patients Improves Mobility at Discharge.

Background and Purpose: Over-sedation may confound neurologic assessment in critically ill neurologic patients and prolong duration of mechanical ventilation (MV). Decreased sedative use may facilitate early functional independence when combined with early mobility. The objective of this study was to evaluate the impact of a stepwise, multidisciplinary analgesia-first sedation pathway and early mobility protocol on medication use and mobility in the neuroscience intensive care unit (ICU). Methods: We performed a single-center prospective cohort study with adult patients admitted to a neuroscience ICU between March and June 2016-2018 who required MV for greater than 48 hours. Patients were included from three separate phases of the study: Phase I - historical controls (2016); Phase II - analgesia-first pathway (2017); Phase III - early mobility protocol (2018). Primary outcomes included propofol requirements during MV, total rehabilitation therapy provided, and functional mobility during ICU admission. Results: 156 patients were included in the analysis. Decreasing propofol exposure was observed during Phase I, II, and III (median 2243.7 mg/day vs 2065.6 mg/day vs 1360.8 mg/day, respectively; P = .04 between Phase I and III). Early mobility was provided in 59.7%, 40%, and 81.6% of patients while admitted to the ICU in Phase I, II, and III, respectively (P < .01). An increased proportion of patients in Phase III were walking or ambulating at ICU discharge (26.7%; 8/30) compared to Phase I (7.9%, 3/38, P = .05). Conclusions: An interdisciplinary approach with an analgesia-first sedation pathway with early mobility protocol was associated with less sedative use, increased rehabilitation therapy, and improved functional mobility status at ICU discharge.

Neuroimaging-based analysis of DBS outcomes in pediatric dystonia: Insights from the GEPESTIM registry.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment in patients of various ages with pharmaco-resistant neurological disorders. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures, and on electrode connectivity to a specific distribution pattern within brain networks. Such information is usually collected using group-level analysis, which relies on the availability of normative imaging resources (atlases and connectomes). Analysis of DBS data in children with debilitating neurological disorders such as dystonia would benefit from such resources, especially given the developmental differences in neuroimaging data between adults and children. We assembled pediatric normative neuroimaging resources from open-access datasets in order to comply with age-related anatomical and functional differences in pediatric DBS populations. We illustrated their utility in a cohort of children with dystonia treated with pallidal DBS. We aimed to derive a local pallidal sweetspot and explore a connectivity fingerprint associated with pallidal stimulation to exemplify the utility of the assembled imaging resources. METHODS: An average pediatric brain template (the MNI brain template 4.5-18.5 years) was implemented and used to localize the DBS electrodes in 20 patients from the GEPESTIM registry cohort. A pediatric subcortical atlas, analogous to the DISTAL atlas known in DBS research, was also employed to highlight the anatomical structures of interest. A local pallidal sweetspot was modeled, and its degree of overlap with stimulation volumes was calculated as a correlate of individual clinical outcomes. Additionally, a pediatric functional connectome of 100 neurotypical subjects from the Consortium for Reliability and Reproducibility was built to allow network-based analyses and decipher a connectivity fingerprint responsible for the clinical improvements in our cohort. RESULTS: We successfully implemented a pediatric neuroimaging dataset that will be made available for public use as a tool for DBS analyses. Overlap of stimulation volumes with the identified DBS-sweetspot model correlated significantly with improvement on a local spatial level (R = 0.46, permuted p = 0.019). The functional connectivity fingerprint of DBS outcomes was determined to be a network correlate of therapeutic pallidal stimulation in children with dystonia (R = 0.30, permuted p = 0.003). CONCLUSIONS: Local sweetspot and distributed network models provide neuroanatomical substrates for DBS-associated clinical outcomes in dystonia using pediatric neuroimaging surrogate data. Implementation of this pediatric neuroimaging dataset might help to improve the practice and pave the road towards a personalized DBS-neuroimaging analyses in pediatric patients.

Gender-specific outcomes of deep brain stimulation for Parkinson's disease - results from a single movement disorder center.

INTRODUCTION AND GOAL: The investigation of gender differences in treatment response is crucial for effective personalized therapies. With only 30%, women are underrepresented in trials for deep brain stimulation (DBS) in Parkinson's disease (PD). It is therefore important to evaluate gender-specific outcomes of DBS in PD in order to improve therapeutic counseling. METHODS: We analyzed clinical outcome parameters of 203 patients with PD that underwent DBS surgery targeting the subthalamic nucleus (STN) at our movement disorder center. A total of 27.6% of patients were female and 72.4% male. Motor and non-motor scores were compared before and 1 year after DBS surgery (1y FU) using Wilcoxon signed-rank tests and gender specific outcomes were analyzed with chi-square tests. RESULTS: At 1y FU, we found significant improvement in UPDRS II, UPDRS III (35.78 ± 36.14% MedOFF vs. StimON-MedOFF), UPDRS IV, depression (BDI-II), and health-related disability as (ADL) that showed no gender-specific differences. No significant change was revealed for UPDRS I, QUIP, and DemTect for the entire cohort. However, when analyzing both groups separately, only women improved in general cognition (plus 1.26 ± 3.03 DemTect points, p = 0.014*), whereas only men ameliorated in depression (minus 1.97 ± 6.92 BDI-II points, p = 0.002**) and impulsivity (minus 2.80 ± 7.27 QUIP points, p = 0.004**). Chi-square tests, however, revealed no significant differences between genders. CONCLUSION AND OUTLOOK: STN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in non-motor-domains like cognition, depressive symptoms, and impulsivity. To explore this in more detail, larger cohorts need to be investigated in multicenter trials.

Christmas-Related Reduction in Beta Activity in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus (STN) beta (13 - 35 Hz) activity is a biomarker reflecting motor state in Parkinson's disease (PD). Adaptive deep brain stimulation (DBS) aims to use beta activity for therapeutic adjustments, but many aspects of beta activity in real-life situations are unknown. OBJECTIVE: The aim was to investigate Christmas-related influences on beta activity in PD. METHODS: Differences in Christmas Day to nonfestive daily averages in chronic biomarker recordings in 4 PD patients with a sensing-enabled STN DBS implant were retrospectively analyzed. Sweet-spot and whole-brain network connectomic analyses were performed. RESULTS: Beta activity was significantly reduced on Christmas Eve in all patients (4.00-9.00 p.m.: -12.30 ± 10.78%, P = 0.015). A sweet spot in the dorsolateral STN connected recording sites to motor, premotor, and supplementary motor cortices. CONCLUSIONS: We demonstrate that festive events can reduce beta biomarker activity. We conclude that circadian and holiday-related changes should be considered when tailoring adaptive DBS algorithms to patient demands. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Automated deep brain stimulation programming based on electrode location: a randomised, crossover trial using a data-driven algorithm.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in controlling motor symptoms in patients with Parkinson's disease. However, correct selection of stimulation parameters is pivotal to treatment success and currently follows a time-consuming and demanding trial-and-error process. We aimed to assess treatment effects of stimulation parameters suggested by a recently published algorithm (StimFit) based on neuroimaging data. METHODS: This double-blind, randomised, crossover, non-inferiority trial was carried out at Charité - Universitätsmedizin, Berlin, Germany, and enrolled patients with Parkinson's disease treated with directional octopolar electrodes targeted at the STN. All patients had undergone DBS programming according to our centre's standard of care (SoC) treatment before study recruitment. Based on perioperative imaging data, DBS electrodes were reconstructed and StimFit was applied to suggest optimal stimulation settings. Patients underwent motor assessments using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) during OFF-medication and in OFF-stimulation and ON-stimulation states under both conditions, StimFit and SoC parameter settings. Patients were randomly assigned (1:1) to receive either StimFit-programmed DBS first and SoC-programmed DBS second, or SoC-programmed DBS first and StimFit-programmed DBS second. The allocation schedule was generated using a computerised random number generator. Both the rater and patients were masked to the sequence of SoC and StimFit stimulation conditions. All patients who participated in the study were included in the analysis. The primary endpoint of this study was the absolute mean difference between MDS-UPDRS-III scores under StimFit and SoC stimulation, with a non-inferiority margin of 5 points. The study was registered at the German Register for Clinical Trials (DRKS00023115), and is complete. FINDINGS: Between July 10, 2020, and Oct 28, 2021, 35 patients were enrolled in the study; 18 received StimFit followed by SoC stimulation, and 17 received SoC followed by StimFit stimulation. Mean MDS-UPDRS-III scores improved from 47·3 (SD 17·1) at OFF-stimulation baseline to 24·7 (SD 12·4) and 26·3 (SD 12·4) under SoC and StimFit stimulation, respectively. Mean difference between motor scores was -1·6 (SD 7·1; 95% CI -4·0 to 0·9; superiority test psuperiority=0·20; n=35), establishing non-inferiority of StimFit stimulation at a margin of -5 points (non-inferiority test pnon-inferiority=0·0038). In six patients (17%), initial programming of StimFit settings resulted in acute side-effects and amplitudes were reduced until side-effects disappeared. INTERPRETATION: Automated data-driven algorithms can predict stimulation parameters that lead to motor symptom control comparable to SoC treatment. This approach could significantly decrease the time necessary to obtain optimal treatment parameters. FUNDING: Deutsche Forschungsgemeinschaft through NeuroCure Clinical Research Center and TRR 295.

Deep brain stimulation in Early Onset Parkinson's disease.

Introduction: Subthalamic Deep Brain Stimulation (STN-DBS) is a safe and well-established therapy for the management of motor symptoms refractory to best medical treatment in patients with Parkinson's disease (PD). Early intervention is discussed especially for Early-onset PD (EOPD) patients that present with an age of onset ≤ 45-50 years and see themselves often confronted with high psychosocial demands. Methods: We retrospectively assessed the effect of STN-DBS at 12 months follow-up (12-MFU) in 46 EOPD-patients. Effects of stimulation were evaluated by comparison of disease-specific scores for motor and non-motor symptoms including impulsiveness, apathy, mood, quality of life (QoL), cognition before surgery and in the stimulation ON-state without medication. Further, change in levodopa equivalent dosage (LEDD) after surgery, DBS parameter, lead localization, adverse and serious adverse events as well as and possible additional clinical features were assessed. Results: PD-associated gene mutations were found in 15% of our EOPD-cohort. At 12-MFU, mean motor scores had improved by 52.4 ± 17.6% in the STIM-ON/MED-OFF state compared to the MED-OFF state at baseline (p = 0.00; n = 42). These improvements were accompanied by a significant 59% LEDD reduction (p < 0.001), a significant 6.6 ± 16.1 points reduction of impulsivity (p = 0.02; n = 35) and a significant 30 ± 50% improvement of QoL (p = 0.01). At 12-MFU, 9 patients still worked full- and 6 part-time. Additionally documented motor and/or neuropsychiatric features decreased from n = 41 at baseline to n = 14 at 12-MFU. Conclusion: The present study-results demonstrate that EOPD patients with and without known genetic background benefit from STN-DBS with significant improvement in motor as well as non-motor symptoms. In line with this, patients experienced a meaningful reduction of additional neuropsychiatric features. Physicians as well as patients have an utmost interest in possible predictors for the putative DBS outcome in a cohort with such a highly complex clinical profile. Longitudinal monitoring of DBS-EOPD-patients over long-term intervals with standardized comprehensive clinical assessment, accurate phenotypic characterization and documentation of clinical outcomes might help to gain insights into disease etiology, to contextualize genomic information and to identify predictors of optimal DBS candidates as well as those in danger of deterioration and/or non-response in the future.

Motor and non-motor improvements following short-term multidisciplinary day-clinic care in Parkinson´s disease.

BACKGROUND: Inpatient as well as outpatient care does often not meet PD-patients' individual needs. INTRODUCTION: Day-clinic concepts encompassing a multidisciplinary team as well as therapy adjustments accompanying everyday demands aim at filling this gap. METHODS: This is a retrospective study on short-term effects of a 3 week multidisciplinary rehabilitation program in patients with Parkinson´s disease (PD) embedded in a specialized movement disorder day-clinic. We analyzed short-term outcome of motor and non-motor symptoms (NMS) in 143 PD-patients (mean age 65.3 ± 11.9 years; Hoehn-and-Yahr-score 2.6 ± 0.7) after 3 weeks with 7.4 ± 1.8 active days of interdisciplinary day-care treatment. Participants attended the day-clinic in groups of five patients at a time. Improvements were evaluated by comparison of standardized physical therapy assessments, disease specific scores for motor symptoms (MDS-UPDRS III), mood (BDI), quality of life (PDQ39, SF36), sleep (PDSS, ESS), impulsiveness (QUIP), apathy (SAS), cognition (MMST), as well as change in medication before and directly after the intervention. RESULTS: MDS-UPDRS motor score improved significantly by 22.9 ± 21.5% (p < 0.001) and was accompanied by a significant reduction of imbalance, immobility, and weakness ranging between 6% and 17% in standardized physical therapy tests. In addition, all disease-specific non-motor scales improved significantly. CONCLUSIONS: A multidisciplinary day-clinic approach can support benefit on motor, non-motor symptoms and QoL in PD-patients. Given the increase in PD incidence and prevalence as well as the significant treatment effects shown here, more day-clinic treatment opportunities ought to be implemented to improve PD treatment adapted to everyday challenges while still reducing costs to the health care system.

Spectral and spatial distribution of subthalamic beta peak activity in Parkinson's disease patients.

Current efforts to optimise subthalamic deep brain stimulation in Parkinson's disease patients aim to harness local oscillatory activity in the beta frequency range (13-35 Hz) as a feedback-signal for demand-based adaptive stimulation paradigms. A high prevalence of beta peak activity is prerequisite for this approach to become routine clinical practice. In a large dataset of postoperative rest recordings from 106 patients we quantified occurrence and identified determinants of spectral peaks in the alpha, low and high beta bands. At least one peak in beta band occurred in 92% of patients and 84% of hemispheres off medication, irrespective of demographic parameters, clinical subtype or motor symptom severity. Distance to previously described clinical sweet spot was significantly related both to beta peak occurrence and to spectral power (rho -0.21, p 0.006), particularly in the high beta band. Electrophysiological landscapes of our cohort's dataset in normalised space showed divergent heatmaps for alpha and beta but found similar regions for low and high beta frequency bands. We discuss potential ramifications for clinicians' programming decisions. In summary, this report provides robust evidence that spectral peaks in beta frequency range can be detected in the vast majority of Parkinsonian subthalamic nuclei, increasing confidence in the broad applicability of beta-guided deep brain stimulation.

Long-term effects of pallidal deep brain stimulation in tardive dystonia: a follow-up of 5-14 years.

INTRODUCTION: Pallidal DBS is an established treatment for severe isolated dystonia. However, its use in disabling and treatment-refractory tardive syndromes (TS) including tardive dyskinesia and tardive dystonia (TD) is less well investigated and long-term data remain sparse. This observational study evaluates long-term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with medically refractory TS. METHODS: We retrospectively analyzed a cohort of seven TD patients with bilateral GPi-DBS. Involuntary movements, dystonia and disability were rated at long-term follow-up (LT-FU) after a mean of 122 ± 33.2 SD months (range 63-171 months) and compared to baseline (BL), short-term (ST-FU; mean 6 ± 2.0 SD months) and 4-year follow-up (4y-FU; mean 45 ± 12.3 SD months) using the Abnormal Involuntary Movement Scale (AIMS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), respectively. Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires, respectively. RESULTS: At LT-FU patients had improved by 73% ± 14.2 SD in involuntary movements and 90% ± 1.0 SD in dystonia. Mood had improved significantly whereas quality of life remained unchanged compared to baseline. No serious long-lasting stimulation-related adverse events (AEs) were observed. Three patients of this cohort presented without active stimulation and ongoing symptom relief at long-term follow-up after 3-10 years of continuous DBS. CONCLUSION: Pallidal DBS is a safe and effective long-term TD treatment. Even more interesting, three of our patients could stop stimulation after several years of DBS without serious relapse. Larger studies need to explore the phenomenon of ongoing symptom relief after DBS cessation.

Subthalamic beta band suppression reflects effective neuromodulation in chronic recordings.

BACKGROUND AND PURPOSE: Biomarkers for future adaptive deep brain stimulation still need evaluation in clinical routine. Here, we aimed to assess stimulation-induced modulation of beta-band activity and clinical symptoms in a Parkinson's disease patient during chronic neuronal sensing using a novel implantable pulse generator. METHODS: Subthalamic activity was recorded OFF and ON medication during a stepwise increase of stimulation amplitude. Off-line fast fourier transfom -based analysis of beta-band activity was correlated with motor performance rated from blinded videos. RESULTS: The stepwise increase of stimulation amplitude resulted in decreased beta oscillatory activity and improvement of bradykinesia. Mean low beta-band (13-20 Hz) activity correlated significantly with bradykinesia (ρ = 0.662, p < 0.01). CONCLUSIONS: Motor improvement is reflected in reduced subthalamic beta-band activity in Parkinson's disease, supporting beta activity as a reliable biomarker. The novel PERCEPT neurostimulator enables chronic neuronal sensing in clinical routine. Our findings pave the way for a personalized precision-medicine approach to neurostimulation.

Long-term effects of pallidal and thalamic deep brain stimulation in myoclonus dystonia.

OBJECTIVE: Observational study to evaluate long-term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the ventral intermediate thalamic nucleus (VIM) on patients with medically refractory myoclonus dystonia (MD). BACKGROUND: More recently, pallidal as well as thalamic DBS have been applied successfully in MD but long-term data are sparse. METHODS: We retrospectively analyzed a cohort of seven MD patients with either separate (n = 1, VIM) or combined GPi- DBS and VIM-DBS (n = 6). Myoclonus, dystonia and disability were rated at baseline (BL), short-term (ST-FU) and long-term follow-up (LT-FU) using the United Myoclonus Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Tsui rating scale, respectively. Quality of life (QoL) and mood were evaluated using the SF-36 and Beck Depression Inventory questionnaires, respectively. RESULTS: Patients reached a significant reduction of myoclonus at ST-FU (62% ± 7.3%; mean ± SE) and LT-FU (68% ± 3.4%). While overall motor BFMDRS changes were not significant at LT-FU, patients with GPi-DBS alone responded better and predominant cervical dystonia ameliorated significantly up to 54% ± 9.7% at long-term. Mean disability scores significantly improved by 44% ± 11.4% at ST-FU and 58% ± 14.8% at LT-FU. Mood and QoL remained unchanged between 5 and up to 20 years postoperatively. No serious long-lasting stimulation-related adverse events were observed. CONCLUSIONS: We present a cohort of MD patients with very long follow-up of pallidal and/or thalamic DBS that supports the GPi as the favourable stimulation target in MD with safe and sustaining effects on motor symptoms (myoclonus>dystonia) and disability.

Fibrinogen Concentrate for the Treatment of Thrombolysis-Associated Hemorrhage in Adult Ischemic Stroke Patients.

In patients with ischemic stroke who receive systemic recombinant tissue plasminogen activator (rt-PA), the risk of secondary hemorrhage is 1-7%. Fibrinogen supplementation with cryoprecipitate is recommended in patients with rt-PA-associated symptomatic hemorrhage. We examined whether fibrinogen concentrate can be used safely in this setting. A single-center retrospective case series was performed in patients who received fibrinogen concentrate for post-rt-PA hemorrhage between January-2012 and December-2017. The primary outcome was the incidence of in-hospital thromboembolic events and infusion reactions. Secondary outcomes included incidence of clinically significant ICH expansion within 24-hours and patient serum fibrinogen response to fibrinogen concentrate therapy. Thromboembolic events occurred in 3 (12.5%) of 24 patients included in the analysis. No patients experienced infusion-related reactions. Five of 22 patients with ICH experienced clinically significant hemorrhage expansion. Hypofibrinogenemia was corrected in 87.5%(7/8) of patients with baseline hypofibrinogenemia, with a median increase in serum fibrinogen 166 mg/dL. Median fibrinogen increase in patients without baseline hypofibrinogenemia was 18 mg/dL. Fibrinogen concentrate is a safe potential therapeutic option to restore fibrinogen levels in acute ischemic stroke patients with thrombolysis-associated hemorrhage.