Lars Timmermann

Purpose: Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are established revascularization strategies, but randomized evidence has often been interpreted without accounting for major changes in CAS technique. We assessed whether the comparative 30-day safety of CAS and CEA differs when trials are stratified by early-device versus contemporary embolic-protected procedural eras. Methods: PubMed, Embase and the Cochrane Library were searched from inception to 1 December 2025 for randomized trials of carotid revascularization in extracranial carotid stenosis. The prespecified novelty of this meta-analysis was era-based stratification according to CAS procedural standards: early-device trials (≤ 2010) versus contemporary embolic-protected CAS trials (≥ 2011), defined by operator credentialing, routine embolic protection, protocolized antiplatelet therapy and contemporary stent platforms. Direct CAS–CEA comparisons were pooled within era-specific strata; trials comparing revascularization with intensive medical therapy were analyzed separately. Fixed-effects models estimated odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was 30-day stroke or death; secondary outcomes included peri-procedural myocardial infarction, cranial nerve injury, fatal or disabling stroke, and long-term ipsilateral stroke. Results: Ten randomized comparisons from nine trials including 14,211 patients were analyzed. In early-device trials, stroke or death occurred in 6.8% after CAS versus 4.4% after CEA (OR 1.72, 95% CI 1.41–2.10). In contemporary embolic-protected CAS–CEA trials, event rates were similarly low and no significant difference was observed (2.9% vs 3.1%; OR 1.29, 95% CI 0.98–1.70). CAS was associated with lower myocardial infarction (OR 0.47, 95% CI 0.31–0.72) and cranial nerve injury (OR 0.06, 95% CI 0.03–0.13). Long-term ipsilateral stroke rates were similar after CAS and CEA, with annualized rates of 0.64% and 0.60% per person-year, respectively (hazard ratio, 1.07; 95% CI, 0.81–1.41). Conclusion: The excess peri-procedural stroke risk associated with CAS in early trials was not observed in contemporary randomized evidence. Contemporary CAS and CEA showed similarly low peri-procedural event rates, supporting comparable safety when CAS is performed according to current procedural standards by experienced operators. These findings suggest that CAS and CEA have comparable peri-procedural safety when performed using contemporary procedural standards, supporting individualized selection of revascularization strategies.

Deep brain stimulation is an effective therapy for tremor in Parkinson’s disease, yet clinical outcomes vary substantially across individuals. This variability highlights the need for continuous and quantitative measures that more accurately capture symptom severity and treatment response. Although precise subthalamic targeting remains fundamental to effective therapy, accounting for network-level modulation of disrupted motor circuits underlying core symptoms may further enhance clinical benefit. Nevertheless, the relative contributions of local and network-level effects to tremor suppression remain unclear, limiting our understanding of the mechanisms driving clinical improvement. In this study, we identified a patient-specific connectivity fingerprint associated with effective tremor suppression following subthalamic deep brain stimulation. Twenty patients with Parkinson’s disease underwent objective tremor quantification using accelerometry during systematic monopolar reviews. For each stimulation setting, the corresponding volume of tissue activated served as a seed for probabilistic tractography, informed by individual diffusion-weighted imaging and subject-specific parcellation of grey and white matter structures. Subsequently, partial least squares regression was employed to analyse over 1,500 stimulation conditions, aiming to identify brain regions whose connectivity patterns predicted tremor outcomes. Ultimately, the resulting network model was compared with a local-effects model to assess whether network mapping provided superior predictive capability for motor improvement compared to traditional local targeting methods. Our results demonstrate that (1) modulation of the basal ganglia and the cerebello-thalamo-cortical circuit at the network level predicts clinical improvement more accurately than local stimulation alone ( P < 0.001); and (2) optimal stimulation sites for tremor relief are located in white-matter regions adjacent to the subthalamic nucleus. Model significance was confirmed through permutation testing ( P < 0.001). Based on these findings, we propose a framework that combines sensor-based measurements with monopolar mapping to investigate the effects of symptom-specific neuromodulation and to guide the selection of connectomic parameters for personalised treatment of motor symptoms.

Background: Processing of emotion plays a critical role in social interaction. People with Parkinson’s Disease (PwPD) may experience impaired facial emotion recognition for negative emotions. Previous evidence regarding the effects of deep brain stimulation in the subthalamic nucleus (STN-DBS) is inconclusive. Objective: To investigate the impact of STN-DBS on emotion processing in PwPD controlling for effects of disease progression and DBS-induced changes in cognitive ability. The secondary aim was to explore the effect of post-DBS adjustments of dopamine replacement therapy. Methods: 32 cognitively intact PwPD (16 DBS, 16 non-DBS) and 22 healthy controls performed tasks assessing recognition and discrimination of emotions and an emotional Go/No-Go paradigm, complemented by task versions using non-emotional stimuli. Baseline assessments were conducted two months before DBS surgery and followed up three months postoperatively. Mixed-effects models analysed group-by-time interactions on task performance measured as accuracy and reaction time. Associations of longitudinal changes in non-motor symptoms and medication dosages with task performance were assessed using bootstrapped Pearson’s correlations. Results: A significant DBS-associated increase in reaction times was found specifically in the emotional conditions, while there was no evidence for a DBS-effect on the accuracy of emotion recognition or discrimination. Post-DBS dose reduction of dopamine agonists was associated with improvement in emotion recognition. Conclusion: STN-DBS does not lead to a generalized decline in emotional processing when controlling for important confounders. Instead, changes in response speed suggest altered processing dynamics. Adjustments in pharmacological treatment regimens contribute to altered FER after DBS surgery.

Background: Severe strokes often require deep sedation, yet the optimal sedation regimen remains unclear. This comparative study compared the efficacy of achieving target sedation depth using inhaled (isoflurane) versus intravenous (propofol) sedation. Methods: This prospective, observational, proof-of-concept study was conducted between July 2022 and June 2023 at two University Hospitals with dedicated neurological intensive care units. We included conservatively treated patients with severe space-occupying strokes (ischemic or haemorrhagic) requiring deep sedation. Patients received either inhaled or intravenous sedation. Sedation targets were defined in the morning rounds using the Richmond-Agitation-Sedation-Scale and were assessed at two subsequent time points (7 p.m. and 7 a.m.) during hospital stay. The primary outcome was the number of days where the predefined sedation target was achieved at both time points, comparing between the two sedation regimens. Secondary and safety outcomes included the incidence of delirium, pneumonia, functional outcomes, mortality, and vasopressor doses. Results: Seventy-nine patients (age 71 [63–81] years, 31 female) were included. Patients sedated with isoflurane achieved the sedation target significantly more often, with 182/444 (41%) compared to 80/497 (16%) assessments in patients sedated with propofol (RR 1.4; 95%-CI: 1.3–1.6). This effect was consistent across all sedation stages, specifically in the deep sedation targets (RR 1.5; 95%-CI: 1.2–1.9) and no-sedation target (RR 5.1; 95%-CI: 2.8–9.4). Secondary and safety outcomes revealed no significant differences. Conclusions: Isoflurane sedation offers a benefit for invasively ventilated stroke patients with respect to sedation targets. Specifically, isoflurane facilitates faster awakening when transitioning from deep sedation to awakening. These data encourage further confirmatory studies for specific stroke-patient groups.

The effect of subthalamic stimulation (STN-DBS) on patients’ personal satisfaction with life and their Parkinson’s disease (PD) treatment is understudied, as is its correlation with quality of life (QoL). Therefore, we tested the hypothesis that STN-DBS for PD enhances satisfaction with life and treatment. In a prospective, multicenter study with a 6-month follow-up involving 121 patients, we measured the main outcomes using the Satisfaction with Life and Treatment Scale (SLTS-7). Secondary outcomes included the eight-item PD Questionnaire (PDQ-8), European QoL Questionnaire (EQ-5D-3L), EQ-Visual Analogue Scale (VAS), Non-Motor Symptom Scale (NMSS), Hospital Anxiety and Depression Scale (HADS), and Unified PD Rating Scale (UPDRS). Longitudinal outcome changes, effect sizes (Cohen’s d), and correlations between outcome changes were analyzed. SLTS-7 scores improved at the 6-month follow-up, particularly in the domains of ‘satisfaction with physical health’ and ‘satisfaction with treatment’. Change scores correlated strongly (EQ-VAS), moderately (PDQ-8 SI and HADS), and weakly (UPDRS-activities of daily living and EQ-5D-3L) with other scales. Satisfaction with physical health, psychosocial well-being, or treatment was not related to UPDRS-motor examination. This study provides evidence that STN-DBS enhances patients’ personal satisfaction with life and treatment. This satisfaction is associated with improvements in the QoL, daily activities, and neuropsychiatric aspects of PD rather than its motor aspects.

Introduction Quality of life (QoL) is of paramount importance as an outcome to monitor and guide therapies for people with Parkinson’s disease (PwPD). In particular, due to the heterogeneous symptoms that PwPD may experience during their disease course, QoL can deteriorate not only in patients but also in their caregivers, with a variety of psychosocial consequences. However, there is a lack of longitudinal studies that explore how QoL evolves over time and what factors are significant. Furthermore, holistic approaches that consider bio-psycho-social determinants are rare. In the worst cases, these gaps can lead to suboptimal care and therefore unmet needs for patients and their caregivers, resulting in unnecessary symptom burden and increased healthcare costs for society. Methods and analysis This prospective, longitudinal study will follow 1000 PwPD along with their caregivers for 20 years, with up to 40 semi-annual assessments. Patient data and sample collection will include clinical assessments, self-reported outcome measures focusing on QoL, biospecimen collection and MRI. Caregiver burden will be systematically assessed through self-administered questionnaires. The use of digitised surveys will allow efficient data collection and convenient assessment at home. Our primary objective is to attain a holistic understanding of QoL in PwPD and establish a tool to measure it. The secondary objective is to explore the psycho-social and biological variables associated with QoL of patients and caregivers over the progression of the disease. This will provide key information for diagnostic and prognostic prediction, therapeutic patient stratification and adaptation of therapy in the future. Ethics and dissemination The study was approved by the local ethics committee of the University Hospital of Marburg (study number: 209/19). The results will be disseminated by means of publication in peer-reviewed journals, international conference contributions, annual patient meetings and a dedicated website. Trial registration number German Clinical Trials Register (DRKS00023598).

Introduction: Recent studies in Parkinson’s disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in separate PD cohorts, indexing dopamine-dependent changes in large-scale brain network dynamics and its implications in clinical features. Methods: We pooled data from two cohorts reflecting early PD. From the Parkinson’s Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) SPECT were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent ¹⁸ F-DOPA-PET imaging. The striatal synthesis capacity of ¹⁸ F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. Results: In both cohorts, dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state (X ² (1, N=79) = 5.82, p = 0.016) and a lower number of transitions (U(N=79) = 337.5, z = −2.06 p= .039) than controls. Significantly, worse motor scores (UPDRS-III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state (UPDRS-III: τ _b (N=63) = −.281; p =.003, DaT putamen: τ _b (N=63)=.213, p = .023, DaT caudate: τ _b (N=63)=.209, p = .025) and a low total number of transitions (UPDRS-III: τb(N=63)= −.308; p = .001, DaT putamen: τ _b (N=63)=.350, p <.001, DaT caudate: τ _b (N=63)=.251, p =.007). Additionally, worse motor performance was associated with a low number of bi-directional transitions between the GI and the lesser connected (LC) state (τ _b (N=63)= −.237; p = .019). These results could not be reproduced in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity or clinical measure were observed. Conclusion: In early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to depend on striatal dopamine availability. Notably, we obtained these results in only one cohort, but not in a replication sample. Key points: Exploring dopamine’s role in brain network dynamics in two Parkinson’s disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity (dFC). In the discovery cohort, results suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control. In the confirmation cohort, these findings were not replicated, indicating PD-specific dFC changes are dependent on unrecognized cohort features.