Aneurysmal Subarachnoid Hemorrhage in Hospitalized Patients on Anticoagulants—A Two Center Matched Case-Control Study

Objective—Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods—Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results—During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS4–5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS1–3) after 12 months. Conclusions—Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients

Infraaurikuläre Fistel als besondere Form der Ohrfehlbildung

Deep brain stimulation (DBS) has become a well-accepted therapy to treat movement disorders, including Parkinson’s disease, essential tremor, and dystonia. Long-term follow-up studies have demonstrated sustained improvement in motor symptoms and quality of life. DBS offers the opportunity to selectively modulate the targeted brain regions and related networks. Moreover, stimulation can be adjusted according to individual patients’ demands, and stimulation is reversible. This has led to the introduction of DBS as a treatment for further neurological and psychiatric disorders and many clinical studies investigating the efficacy of stimulating various brain regions in order to alleviate severe neurological or psychiatric disorders including epilepsy, major depression, and obsessive–compulsive disorder. In this review, we provide an overview of accepted and experimental indications for DBS therapy and the corresponding anatomical targets

Body mass index and leptin levels in serum and cerebrospinal fluid in relation to delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is associated with a high mortality rate and may leave surviving patients severely disabled. After the initial hemorrhage, clinical outcome is further compromised by the occurrence of delayed cerebral ischemia (DCI). Overweight and obesity have previously been associated with protective effects in the post-bleeding phase. The aim of this study was to assess the effects of a patient's body mass index (BMI) and leptin levels on the occurrence of DCI, DCI-related cerebral infarction, and clinical outcome. In total, 263 SAH patients were included of which leptin levels were assessed in 24 cases. BMI was recorded along disease severity documented by the Hunt and Hess and modified Fisher scales. The occurrence of clinical or functional DCI (neuromonitoring, CT Perfusion) was assessed. Long-term clinical outcome was documented after 12 months (extended Glasgow outcome scale). A total of 136 (51.7%) patients developed DCI of which 72 (27.4%) developed DCI-related cerebral infarctions. No association between BMI and DCI occurrence (P = .410) or better clinical outcome (P = .643) was identified. Early leptin concentration in serum (P = .258) and CSF (P = .159) showed no predictive value in identifying patients at risk of unfavorable outcomes. However, a significant increase of leptin levels in CSF occurred from 326.0 pg/ml IQR 171.9 prior to DCI development to 579.2 pg/ml IQR 211.9 during ongoing DCI (P = .049). In our data, no association between obesity and clinical outcome was detected. After DCI development, leptin levels in CSF increased either by an upsurge of active transport or disruption of the blood-CSF barrier. This trial has been registered at ClinicalTrials.gov (NCT02142166) as part of a larger-scale prospective data collection. BioSAB: https://clinicaltrials.gov/ct2/show/NCT02142166

Cognitive effects of deep brain stimulation for essential tremor: evaluation at 1 and 6 years

Only a few studies have explored cognitive changes with deep brain stimulation (DBS) in patients with essential tremor (ET). Furthermore, the cognitive effects after years of electrical stimulation are unknown. Assessing the impact of stereotactic electrode implantation and the actual electrical stimulation on cognition in patients with ET in the short and long term is of interest, because DBS is increasingly applied and can offer deeper insight into human brain functions. We examined nine ET patients before surgery (PRE-SURGERY), and 1 and 6 years thereafter with DBS switched on (DBS-ON) and off (DBS-OFF). Standardized neuropsychological tests and reaction time tests were applied. There were no differences in tasks of verbal fluency, memory, and executive and intellectual functions comparing PRE-SURGERY, DBS-ON, and DBS-OFF at 1 and 6 years post-surgery. Imaging data revealed that the dorsolateral prefrontal cortex and mamillo-thalamic tracts crucial for cognitive functioning were spared by electrode implantation. Additionally, with electrodes targeting the thalamus and adjacent subthalamic area, the actual electrical stimulation did not affect neuropsychological functioning. However, lesions caused by electrode implantation led to an increase in simple reaction time, while the actual electrical stimulation restored impaired reaction time. This is the second largest study of neuropsychological functioning in patients with ET treated with DBS, and the first covering a neuropsychological long-term follow-up over 6 years. Neither stereotactic surgery nor electrical stimulation affected higher cognitive processes. This study proposes that cerebello-thalamo-cortical pathways in humans are involved in tasks of simple reaction time

Circulatory dipeptidyl peptidase 3 (cDPP3) is a potential biomarker for early detection of secondary brain injury after aneurysmal subarachnoid hemorrhage

Introduction: Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH. Materials and methods: cDPP3 levels were quantified in serum obtained from 96 confirmed aSAH patients during the early (EP: d(1-4)), critical (CP: d(5-8), d(9-12), d(13-15)) and late (LP: d(16-21)) phase after aSAH onset. Associations between cDPP3 levels and demographic or clinical parameters were evaluated. The relations between cDPP3 levels and DCI, DCI-related infarctions and long-term clinical outcomes were examined by receiver operating characteristics (ROC) curve analysis and multivariate logistic regression. Results: Significantly higher cDPP3 levels during CP (d(5-8), d(9-12), d(13-15)) were observed in patients with poor clinical (p < 0.001 top = 0.033) or radiological (p = 0.012 top = 0.039) status on admission, DCI (p < 0.001 top = 0.001), DCI-related infarctions (p = 0.002 top = 0.007), and poorer long-term outcome (p = 0.007 top = 0.019). ROC curve analysis indicated that higher cDPP3 levels on d(5-8) are predictive for a poor clinical outcome (area under the curve = 0.677, p = 0.007). In multivariate analysis, there was an independent association between cDPP3 levels on d(5-8) and development of DCI-related infarctions (p = 0.038). Conclusion: Our results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients

Systemic and Cerebral Concentration of Nimodipine During Established and Experimental Vasospasm Treatment

BACKGROUND: Oral nimodipine is an established prophylactic agent for cerebral vasospasm after subarachnoid hemorrhage (SAH). In highly selected cases, intra-arterial (IA) or intravenous (IV) application of nimodipine may be considered; however, the optimum dosage and modality of application remain a matter of debate. The purpose of this investigation is analysis of nimodipine concentration in serum, cerebrospinal fluid, and cerebral microdialysate in the context of currently effective dose and route of application (oral, IA, IV). METHODS:We prospectively collected 156 samples from 37 patients treated for aneurysmal SAH from May 2014 to July 2015. Treatment groups were stratified according to modality of application and low-dose or high-dose treatment. At time of sampling, current dose and modality of application effectively sustained cerebral perfusion as documented by common diagnostics. Samples were analyzed for nimodipine concentration via high-performance liquid chromatography and tandem mass spectrometry. RESULTS: In most cases (94.3%), nimodipine remained below the limit of quantification (0.5 ng/mL) within the brain (microdialysis, cerebrospinal fluid), even during targeted, local application (IA nimodipine). The median serum concentration for all treatment groups was 17.3 ng/mL. Modality of application (oral, IA, IV) was not associated with significant differences in serum concentrations (P = 0.712), even after stratification for dosage (P = 0.371), implying a comparable systemic distribution, if not efficacy. CONCLUSIONS: Nimodipine does not accumulate sufficiently within the target organ for treatment monitoring. Comparable systemic concentrations can be observed irrespective of application modality and dosing. Future studies will clarify the role of efficacy-driven treatment algorithms, in which lowest dose and least invasive mode of application still effective should be identified

Aneurysmal Subarachnoid Hemorrhage in Hospitalized Patients on Anticoagulants—A Two Center Matched Case-Control Study

Objective—Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods—Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results—During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS4–5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS1–3) after 12 months. Conclusions—Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients

Parenthood and neurosurgery in Europe, a white paper from the European association of neurosurgical societies’ diversity in neurosurgery committee, part II – practice with children

Introduction: In the first part of this White Paper, the European Association of Neurosurgical Societies (EANS) Diversity in Neurosurgery Committee (DC) addressed the obstacles faced by neurosurgeons when planning to have a family and practice during pregnancy, attempting to enumerate potential, easily implementable solutions for departments to be more family-friendly and retain as well as foster talent of parent-neurosurgeons, regardless of their gender identity and/or sexual orientation. Attrition avoidance amongst parent-neurosurgeons is at the heart of these papers. Research question: In this second part, we address the obstacles posed by practice with children and measures to mitigate attrition rates among parent-neurosurgeons. For the methodology employed to compose this White Paper, please refer to Supplementary Electronic Materials (SEM) 1. Materials and methods: For composing these white papers, the European Association of Neurosurgical Societies (EANS)'s Diversity Committee (DC) recruited neurosurgeon volunteers from all member countries, including parents, aspiring parents, and individuals without any desire to have a family to create a diverse and representative working group (WG). Results: In spite of the prevailing heterogeneity in policies across the continent, common difficulties can be identified for both mothers and fathers considering the utilization of parental leave. Discussion and conclusion: Reconciliation of family and a neurosurgical career is challenging, especially for single parents. However, institutional support in form of childcare facilities and/or providers, guaranteed lactation breaks and rooms, flexible schedule models including telemedicine, and clear communication of policies can improve working conditions for parent-neurosurgeons, avoid their attrition, and foster family-friendly work environments