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.

Parenthood and neurosurgery in Europe a white paper from the European Association of Neurosurgical Societies' Diversity in Neurosurgery Committee Part I - Family Planning and Practice during Pregnancy.

Introduction: Family and work have immensely changed and become intertwined over the past half century for both men and women. Additionally, alongside to traditional family structures prevalent, other forms of families such as single parents, LGBTQ + parents, and bonus families are becoming more common. Previous studies have shown that surgical trainees regularly leave residency when considering becoming a parent due to the negative stigma associated with pregnancy during training, dissatisfaction with parental leave options, inadequate lactation and childcare support, and desire for greater mentorship on work-life integration. Indeed, parenthood is one of the factors contributing to attrition in surgical specialities, neurosurgery not being an exception. Research question: The Diversity in Neurosurgery Committee (DC) of the European Association of Neurosurgical Societies (EANS) recognizes the challenges individuals face in parenthood with neurosurgery and wishes to address them in this white paper. Materials and methods: In the following sections, the authors will focus on the issues pertaining to family planning and neurosurgical practice during pregnancy in itemized fashion based on an exhaustive literature search and will make recommendations to address the matters raised. Results: Potential solutions would be to further improve the work-family time ration as well as improving working conditions in the hospital. Discussion and conclusion: While many obstacles have been quoted in the literature pertaining to parenthood in medicine, and in neurosurgery specifically, initiatives can and should be undertaken to ensure not only retention of colleagues, but also to increase productivity and job satisfaction of those seeking to combine neurosurgery and a family life, regardless of their sexual identity and orientation.

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.

Seizure after surgical treatment of chronic subdural hematoma-Associated factors and effect on outcome.

Introduction: Chronic subdural hematoma (cSDH) is becoming more prevalent due to population aging and the increasing use of antithrombotic drugs. Postoperative seizure in cSDH have a negative effect on outcome, and there currently no consensus regarding prophylactic anti-epileptic drug (AED) treatment. The objective of this study was to evaluate predisposing and triggering factors associated with postoperative epileptic seizure in patients with cSDH. Methods: All patients, who were surgically treated for cSDH in a single tertiary care center between 2015 and 2019, were considered for inclusion. Relevant patient- and hematoma-specific characteristics were retrospectively extracted from hospital records. Paroxysmal events categorized by the treating physician as suspected postoperative seizures were noted. The clinical outcome was extracted from the last available follow-up visit and classified according to the Glasgow outcome scale (GOS). Results: Of the included 349 patients, 54 (15.5%) developed suspected postoperative epileptic complications in the form of early seizure (≤ 7 days) in 11 patients (3.2%) and late seizure (>7 days) in 43 patients (12.3%). In the logistic regression analysis, solely depressed brain volume (supratentorial volume (ml) not filled with re-expanded brain) was independently associated with postoperative seizure (odds ratio [OR] 1.006, 95% CI: 1.001-1.011; p = 0.034). The occurrence of postoperative seizure (OR 6.210, 95% CI: 2.704-14.258; p < 0.001) and preoperative Markwalder grading (OR 2.919, 95% CI: 1.538-5.543; p = 0.001) were independently associated with unfavorable (GOS1-3) outcome. Conclusion: Larger postoperative depressed brain volume was the only factor independently associated with suspected postoperative seizure, and it could help identify a subgroup of patients with higher susceptibility to epileptic events. Based on our data, no formal recommendation can be made regarding the prophylactic use of anti-epileptic drugs. Nevertheless, the relative safety of new generation AEDs and the detrimental effect of postoperative seizure on outcome may justify its use in a selected patient population.

Revisiting the Timeline of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Toward a Temporal Risk Profile.

BACKGROUND: Delayed cerebral ischemia (DCI) is one of the main determinants of clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). The classical description of risk for DCI over time is currently based on the outdated concept of angiographic vasospasm. The goal of this study was to assess the temporal risk profile of DCI, defined by extended clinical and radiological criteria, as well as the impact the time point of DCI onset has on clinical outcome. METHODS: All patients with aneurysmal SAH referred to a single tertiary care center between 2010 and 2018 were considered for inclusion. This study was designed as a retrospective cohort analysis and data were extracted from existing patient files. In conscious patients, DCI was diagnosed clinically, and in unconscious patients, diagnosis was based on perfusion computed tomography imaging and multimodal neuromonitoring. Extended Glasgow Outcome Scale scores were assessed after 12 months and compared between patients with early (< day 7) and late (≥ day 7) DCI onset. RESULTS: The median delay from day of the hemorrhage (day 0) until detection of the first DCI event was 7.0 days, with an interquartile range of 5 days. The probability of DCI development over time demonstrated a bimodal distribution with a peak risk on day 5 (0.084; confidence interval 0.05.5-0.122) and a second peak on day 9 (0.077; confidence interval 0.045-0.120). A total of 27 patients (15.6%) suffered dominant hemispheric or severe bilateral DCI-related infarctions, resulting in the withdrawal of technical life support. Of those, the majority (20 patients, 22.2%) presented with early DCI onset (vs. late onset: 7 patients, 8.4%; p = 0.013). CONCLUSIONS: The risk profile of DCI over time mirrors the description of angiographic vasospasm; however, it comes with an added timely delay of 1 to 2 days. Early occurrence of DCI (before day 7) is associated with a higher infarct load and DCI-related mortality. Although the exact causal relationship remains to be determined, the time point of DCI onset may serve as an independent prognostic criterion in decision-making.

Decompressive hemicraniectomy after aneurysmal subarachnoid hemorrhage-justifiable in light of long-term outcome?

PURPOSE: Decompressive hemicraniectomy (DHC) is a potentially lifesaving procedure in refractory intracranial hypertension, which can prevent death from brainstem herniation but may cause survival in a disabled state. The spectrum of indications is expanding, and we present long-term results in a series of patients suffering from aneurysmal subarachnoid hemorrhage (SAH). METHODS: We performed a retrospective analysis of previously registered data including all patients treated for SAH between 2010 and 2018 in a single institution. Patients treated with decompressive hemicraniectomy due to refractory intracranial hypertension were identified. Clinical outcome was assessed by means of the Glasgow outcome scale after 12 months. RESULTS: Of all 341 SAH cases, a total of 82 (24.0%) developed intracranial hypertension. Of those, 63 (18.5%) patients progressed into refractory ICP elevation and were treated with DHC. Younger age (OR 0.959, 95% CI 0.933 to 0.984; p = 0.002), anterior aneurysm location (OR 0.253, 95% CI 0.080 to 0.799; 0.019; p = 0.019), larger aneurysm size (OR 1.106, 95% CI 1.025 to 1.194; p = 0.010), and higher Hunt and Hess grading (OR 1.944, 95% CI 1.431 to 2.641; p < 0.001) were independently associated with the need for DHC. After 1 year, 10 (15.9%) patients after DHC were categorized as favorable outcome. Only younger age was independently associated with favorable outcome (OR 0.968 95% CI 0.951 to 0.986; p = 0.001). CONCLUSIONS: Decompressive hemicraniectomy, though lifesaving, has only a limited probability of survival in a clinically favorable condition. We identified young age to be the sole independent predictor of favorable outcome after DHC in SAH.

Risk factors of recurrence in chronic subdural hematoma and a proposed extended classification of internal architecture as a predictor of recurrence.

Chronic subdural hematomas (cSDHs) constitute one of the most prevalent intracranial disease entities requiring surgical treatment. Although mostly taking a benign course, recurrence after treatment is common and associated with additional morbidity and costs. Aim of this study was to develop hematoma-specific characteristics associated with risk of recurrence. All consecutive patients treated for cSDH in a single university hospital between 2015 and 2019 were retrospectively considered for inclusion. Size, volume, and midline shift were noted alongside relevant patient-specific factors. We applied an extended morphological classification system based on internal architecture in CT imaging consisting of eight hematoma subtypes. A logistic regression model was used to assess the classification's performance on predicting hematoma recurrence. Recurrence was observed in 122 (32.0%) of 381 included patients. Apart from postoperative depressed brain volume (OR 1.005; 95% CI 1.000 to 1.010; p = 0.048), neither demographic nor factors related to patient comorbidity affected recurrence. The extended hematoma classification was identified as a significant predictor of recurrence (OR 1.518; 95% CI 1.275 to 1.808; p < 0.001). The highest recurrence rates were observed in hematomas of the homogenous (isodense: 41.4%; hypodense: 45.0%) and sedimented (50.0%) types. Our results support that internal architecture subtypes might represent stages in the natural history of chronic subdural hematoma. Detection and treatment at a later stage of spontaneous repair can result in a reduced risk of recurrence. Based on their high risk of recurrence, we advocate follow-up after treatment of sedimented and homogenous hematomas.

Incremental Versus Immediate Induction of Hypertension in the Treatment of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a common complication of aneurysmal subarachnoid hemorrhage and contributes to unfavorable outcome. In patients with deterioration despite prophylactic nimodipine treatment, induced hypertension (iHTN) can be considered, although the safety and efficacy of induction are still a matter of debate. In this study, two iHTN treatment algorithms were compared with different approaches toward setting pressure targets. METHODS: In a cohort of 325 consecutive patients with subarachnoid hemorrhage, 139 patients were treated by induced hypertension as a first tier treatment. On diagnosing DCI, blood pressure was raised via norepinephrine infusion in 20-mm Hg increments in 37 patients (iHTNincr), whereas 102 patients were treated by immediate elevation to systolic pressure above 180 mm Hg (iHTNimm). Treatment choice was based on personal preference of the treating physician but with a gradual shift away from incremental elevation. Both groups were evaluated for DCI-caused infarction, the need of additional endovascular rescue treatment, the occurrence of pressor-treatment-related complications, and clinical outcome assessed by the extended Glasgow outcome scale after 12 months. RESULTS: The rate of refractory DCI requiring additional rescue therapy was comparable in both groups (48.9% in iHTNincr, 40.0% in iHTNimm; p = 0.332). The type of induced hypertension was not independently associated with the occurrence of DCI-related infarction in a logistic regression model (odds ratio 1.004; 95% confidence interval 0.329-3.443; p = 0.942). Similar rates of pressor-treatment-related complications were observed in both treatment groups. Favorable outcome was reached in 44 (43.1%) patients in the immediate vs. 10 (27.0%) patients in the incremental treatment group (p = 0.076). However, only Hunt and Hess grading was identified as an independent predictor variable of clinical outcome (odds ratio 0.422; 95% confidence interval 0.216-0.824; p = 0.012). CONCLUSIONS: Immediate induction of hypertension with higher pressure targets did not result in a lower rate of DCI-related infarctions but was not associated with a higher complication rate compared with an incremental approach. Future tailored blood pressure management based on patient- and time-point-specific needs will hopefully better balance the neurological advantages versus the systemic complications of induced hypertension.

Invasive Multimodal Neuromonitoring in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.

Background and Purpose: Aneurysmal subarachnoid hemorrhage is a devastating disease leaving surviving patients often severely disabled. Delayed cerebral ischemia (DCI) has been identified as one of the main contributors to poor clinical outcome after subarachnoid hemorrhage. The objective of this review is to summarize existing clinical evidence assessing the diagnostic value of invasive neuromonitoring (INM) in detecting DCI and provide an update of evidence since the 2014 consensus statement on multimodality monitoring in neurocritical care. Methods: Three invasive monitoring techniques were targeted in the data collection process: brain tissue oxygen tension (ptiO2), cerebral microdialysis, and electrocorticography. Prospective and retrospective studies as well as case series (≥10 patients) were included as long as monitoring was used to detect DCI or guide DCI treatment. Results: Forty-seven studies reporting INM in the context of DCI were included (ptiO2: N=21; cerebral microdialysis: N=22; electrocorticography: N=4). Changes in brain oxygen tension are associated with angiographic vasospasm or reduction in regional cerebral blood flow. Metabolic monitoring with trend analysis of the lactate to pyruvate ratio using cerebral microdialysis, identifies patients at risk for DCI. Clusters of cortical spreading depolarizations are associated with clinical neurological worsening and cerebral infarction in selected patients receiving electrocorticography monitoring. Conclusions: Data supports the use of INM for the detection of DCI in selected patients. Generalizability to all subarachnoid hemorrhage patients is limited by design bias of available studies and lack of randomized trials. Continuous data recording with trend analysis and the combination of INM modalities can provide tailored treatment support in patients at high risk for DCI. Future trials should test interventions triggered by INM in relation to cerebral infarctions.

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.

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: d1-4), critical (CP: d5-8, d9-12, d13-15) and late (LP: d16-21) 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 (d5-8, d9-12, d13-15) were observed in patients with poor clinical (p < 0.001 to p = 0.033) or radiological (p = 0.012 to p = 0.039) status on admission, DCI (p < 0.001 to p = 0.001), DCI-related infarctions (p = 0.002 to p = 0.007), and poorer long-term outcome (p = 0.007 to p = 0.019). ROC curve analysis indicated that higher cDPP3 levels on d5-8 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 d5-8 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.

Retinal Vessel Analysis (RVA) in the Context of Subarachnoid Hemorrhage - A Proof of Concept Study.

BACKGROUND: Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH. METHODS: In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2-14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling. RESULTS: Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion. CONCLUSION: RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.

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.