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Introduction Non-vitamin K-antagonist oral anticoagulants (NOAC) have become first choice oral anticoagulant (OAC) with decreasing use of vitamin K antagonists (VKA), partly due to lower risk of intracerebral hemorrhage (ICH). Aim: to identify trends in sale of OACs and relate them to trends in OAC-related ICH (OAC-ICH). Patients and methods Study was based on the population in the Capital Region of Denmark (1.8 million inhabitants). We identified all patients admitted with a non-traumatic OAC-ICH in 2010–2017 and ascertained diagnosis and drug use through medical charts. We used information available in the public domain on sale of defined daily doses (DDD) of OAC in the Capital Region of Denmark. Results 453 patients with OAC-ICH out of a total of 2877 ICH-events were identified. From 2010 to 2017 sale of NOAC rose from 0.1 to 11.8 DDD/1000 inhabitants/day (p Discussion In Denmark, the population on OACs has increased; resulting from increased use of NOACs. Parallel to this development, the proportion of OAC-ICH overall has increased based on an increasing trend in NOAC-related ICH. Conclusion Our findings document a need for further research on prevention and treatment of this complication.

OBJECTIVEDecompressive craniectomy (DC) is an emergency neurosurgical procedure used in cases of severe intracranial hypertension or impending intracranial herniation. The procedure is often lifesaving, but it exposes the brain to atmospheric pressure in the subsequent rehabilitation period, which changes intracranial physiology and probably leads to complications such as hydrocephalus, hygromas, and “syndrome of the trephined.” The objective of the study was to study the effect of cranioplasty on intracranial pressure (ICP), postural ICP changes, and intracranial pulse wave amplitude (PWA).METHODSThe authors performed a prospective observational study including patients who underwent DC during a 12-month period. Telemetric ICP sensors were implanted in all patients at the time of DC. ICP was evaluated before and after cranioplasty during weekly measurement sessions including a standardized postural change program.RESULTSTwelve of the 17 patients enrolled in the study had cranioplasty performed and were included in the present investigation. Their mean ICP in the supine position increased from –0.5 ± 4.8 mm Hg the week before cranioplasty to 6.3 ± 2.5 mm Hg the week after cranioplasty (p < 0.0001), whereas the mean ICP in the sitting position was unchanged (–1.2 ± 4.8 vs –1.1 ± 3.6 mm Hg, p = 0.90). The difference in ICP between the supine and sitting positions was minimal before cranioplasty (1.1 ± 1.8 mm Hg) and increased to 7.4 ± 3.6 mm Hg in the week following cranioplasty (p < 0.0001). During the succeeding 2 weeks of the follow-up period, the mean ICP in the supine and sitting positions decreased in parallel to, respectively, 4.6 ± 3.0 mm Hg (p = 0.0003) and –3.9 ± 2.7 mm Hg (p = 0.040), meaning that the postural ICP difference remained constant at around 8 mm Hg. The mean intracranial PWA increased from 0.7 ± 0.7 mm Hg to 2.9 ± 0.8 mm Hg after cranioplasty (p < 0.0001) and remained around 3 mm Hg throughout the following weeks.CONCLUSIONSCranioplasty restores normal intracranial physiology regarding postural ICP changes and intracranial PWA. These findings complement those of previous investigations on cerebral blood flow and cerebral metabolism in patients after decompressive craniectomy.

Introduction Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarniet alcreated the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for ETV and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. Methods and analysis The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients≥18 years of age treated with ETV at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. Ethics and dissemination The study is approved by appropriate ethics or patient safety boards in all participating countries. Trial registration number NCT04773938; Pre-results.

Background: Available nomograms to predict aortic root (AoR) diameter for body surface area have limitations. The purpose of this study was to evaluate the use of a new multivariate predictive model to identify AoR dilatation in hypertensive patients with left ventricular hypertrophy. Methods: 943 of 961 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic sub-study had the necessary baseline characteristics and echocardiographic 2D measurements of AoR size to be included. Results: Predicted AoR (Sinus of Valsalva) diameter was 1.519 + (age [years] × 0.010) + (height [cm] × 0.010) – (gender [1 = M, 2 = F] × 0.247), and a measured AoR diameter exceeding the 97.5-percentile of this estimate was considered dilated. Measured AoR diameter was larger in men than in women (3.75 vs. 3.48 cm, p < 0.001) and AoR diameter predicted by the model was larger than predicted by nomogram (3.52 vs. 3.28 cm, p < 0.001). Using the multivariate model to identify patients with AoR dilatation, the prevalence was 13.7% in men and 12.3% in women (p = 0.537). There was consensus of AoR phenotype (normal/dilated) between model and nomogram in 92.8% of the patients. In multivariate logistic regression, AoR dilatation by model definition was predicted by presence of aortic regurgitation (OR 2.67, p < 0.001) and SD increase in age (OR 0.75, p = 0.023), pulse pressure (OR 0.64, p < 0.001), left ventricular mass index (OR 1.36, p = 0.08) and stroke volume (OR 1.45, p = 0.002), but not by body weight. Conclusions: Using the proposed model the prevalence of AoR dilatation was equal in men and women and the model seems to address the effects of gender, age and body size on AoR size. Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00338260.

Background: The standard lumbar puncture position involves maximum flexion of both lumbar and cervical spine. The cerebrospinal fluid opening pressure (CSFop) is measured in a horizontal position. This study investigated if flexion of hip and neck both separately and simultaneously influence intracranial pressure (ICP) to a clinically relevant extent. Methods: Thirty-nine patients, undergoing invasive ICP monitoring as part of diagnostic work-up, were included. The patients underwent either a vertical postural examination (n = 24) or a horizontal postural examination (n = 15) to examine a varying degree of spine flexion. Results: The vertical examination showed that ICP decreased by 15.2 mmHg when straightening the neck in a sitting lumbar puncture position (n = 24, IQR − 20.1 to − 9.7). In the horizontal examination, ICP increased in all but one patient when changing from supine position to lateral recumbent position (n = 15, median increase of 6.9 mmHg, IQR 3.1 to 9.9). Straightening the hips alone decreased ICP with 0.2 mmHg (n = 15, IQR − 0.5 to 2.0), while straightening the neck alone decreased ICP by 4.0 mmHg (n = 15, IQR − 5.9 to − 1.7). However, when straightening the hip and neck simultaneously ICP decreased by 6.4 mmHg (n = 6, IQR − 9.5 to − 4.4). Conclusions: Neck flexion alone, and neck flexion and hip flexion in combination, has significant confounding influence on ICP. This may cause patients to shift from a normal ICP range to a pathological ICP range, which will potentially affect treatment decisions. Consensus on guidelines for body position including neck and hip flexion measuring CSFop may be needed.

Background Decompressive craniectomy (DC) is used in cases of severe intracranial hypertension or impending intracranial herniation. DC effectively lowers intracranial pressure (ICP) but carries a risk of severe complications related to abnormal ICP and/or cerebrospinal fluid (CSF) circulation, eg, hygroma formation, hydrocephalus, and "syndrome of the trephined." Objective To study the long-term effect of DC on ICP, postural ICP regulation, and intracranial pulse wave amplitude (PWA). Methods Prospective observational study including patients undergoing DC during a 12-mo period. Telemetric ICP sensors (Neurovent-P-tel; Raumedic, Helmbrechts, Germany) were implanted in all patients. Following discharge from the neuro intensive care unit (NICU), scheduled weekly ICP monitoring sessions were performed during the rehabilitation phase. Results A total of 16 patients (traumatic brain injury: 7, stroke: 9) were included (median age: 55 yr, range: 19-71 yr). Median time from NICU discharge to cranioplasty was 48 d (range: 16-98 d) and during this period, mean ICP gradually decreased from 7.8 ± 2.0 mm Hg to -1.8 ± 3.3 mm Hg (P = .02). The most pronounced decrease occurred during the first month. Normal postural ICP change was abolished after DC for the entire follow-up period, ie, there was no difference between ICP in supine and sitting position (P = .67). PWA was markedly reduced and decreased from initially 1.2 ± 0.7 mm Hg to 0.4 ± 0.3 mm Hg (P = .05). Conclusion Following NICU discharge, ICP decreases to negative values within 4 wk, normal postural ICP regulation is lost and intracranial PWA is diminished significantly. These abnormalities might have implications for intracranial fluid movements (eg, CSF and/or glymphatic flow) following DC and warrants further investigations.

Objectives Suboccipital decompressive craniectomy (SDC) is considered the best treatment option in patients with space-occupying cerebellar infarction and clinical signs of deterioration. The primary purpose of this study was to evaluate long-term functional outcome in patients one year after SDC for space-occupying cerebellar infarction, and secondly, to determine factors associated with outcome. Patients and methods All patients treated with SDC due to space-occupying cerebellar infarction between January 2009 and October 2015 were included in the study. Data was retrospectively collected from patient records, CT/MRI scans and surgical protocols. Long-term functional outcome was determined by the modified Rankin Scale (mRS) and mRS ≥ 4 was defined as unfavorable outcome. Results Twenty-two patients (16 male, 6 female) were included in the study. Median age was 53 years. Nine patients were treated with external ventricular drainage as an initial treatment attempt prior to SDC. Median time from symptom onset (stroke ictus) to initiation of the SDC surgery was 48 h (IQR 28–99 hours) and median GCS before SDC was 8 (IQR 5–10). At follow up, median mRS was 3 (IQR 2–6). Outcome was favorable (mRS 0–3) in 12 patients and unfavorable in 10 (3 with major disability, 7 dead). Brainstem infarction and bilateral cerebellar infarction were associated with unfavorable outcome. Conclusions In this small study, functional long-term outcome in patients with space-occupying cerebellar infarction treated by SDC was acceptable and comparable to previously published results (favorable outcome in 54% of patients). Brainstem infarction and bilateral cerebellar infarction were associated with unfavorable outcome.

Intracranial pressure (ICP)-derived indices of cerebrovascular reactivity (e.g., PRx, PAx, and RAC) have been developed to improve understanding of brain status from available neuromonitoring variables. These indices are moving correlation coefficients between slow-wave vasogenic fluctuations in ICP and arterial blood pressure. In this retrospective analysis of neuromonitoring data from 200 patients admitted with moderate/severe traumatic brain injury (TBI), we evaluate the predictive value of CPPopt based on these ICP-derived indices of cerebrovascular reactivity. Valid CPPopt values were obtained in 92.3% (PRx), 86.7% (PAX), and 84.6% (RAC) of the monitoring periods, respectively. In multivariate logistic analysis, a baseline model that includes age, sex, and admission Glasgow Coma Score had an area under the receiver operating curve of 0.762 (P0.0001) for dichotomous outcome prediction (dead vs. good recovery). When adding time/dose of CPP below CPPopt, all multivariate models (based on PRx, PAx, and RAC) predicted the dichotomous outcome measure, but additional value of the prediction was only significantly added by the PRx-based calculations of time spent with CPP below CPPopt and dose of CPP below CPPopt.

Supplemental material, sj-pdf-1-eso-10.1177_23969873211008770 for Trends in incidence of oral anticoagulant-related intracerebral hemorrhage and sales of oral anticoagulants in Capital Region of Denmark 2010–2017 by Josefine Grundtvig, Christian Ovesen, Inger Havsteen, Thomas Christensen, David Gaist, Helle K Iversen, Christina Kruuse, Alexander Lilja-Cyron, Karen Ægidius, Sverre Rosenbaum, Per Meden, Jacob Marstrand, Louisa Christensen, Thorsten Steiner and Hanne Christensen: ; for the PHYS-Stroke study group in European Stroke Journal

Intracranial pressure (ICP)–derived indices of cerebrovascular reactivity (e.g., PRx, PAx, and RAC) have been developed to improve understanding of brain status from available neuromonitoring variables. These indices are moving correlation coefficients between slow-wave vasogenic fluctuations in ICP and arterial blood pressure. In this retrospective analysis of neuromonitoring data from 200 patients admitted with moderate/severe traumatic brain injury (TBI), we evaluate the predictive value of CPPopt based on these ICP-derived indices of cerebrovascular reactivity. Valid CPPopt values were obtained in 92.3% (PRx), 86.7% (PAX), and 84.6% (RAC) of the monitoring periods, respectively. In multivariate logistic analysis, a baseline model that includes age, sex, and admission Glasgow Coma Score had an area under the receiver operating curve of 0.762 (P < 0.0001) for dichotomous outcome prediction (dead vs. good recovery). When adding time/dose of CPP below CPPopt, all multivariate models (based on PRx, PAx, and RAC) predicted the dichotomous outcome measure, but additional value of the prediction was only significantly added by the PRx-based calculations of time spent with CPP below CPPopt and dose of CPP below CPPopt.

The standard lumbar puncture position involves maximum flexion of both lumbar and cervical spine. The cerebrospinal fluid opening pressure (CSFThirty-nine patients, undergoing invasive ICP monitoring as part of diagnostic work-up, were included. The patients underwent either a vertical postural examination (n = 24) or a horizontal postural examination (n = 15) to examine a varying degree of spine flexion.The vertical examination showed that ICP decreased by 15.2 mmHg when straightening the neck in a sitting lumbar puncture position (n = 24, IQR - 20.1 to - 9.7). In the horizontal examination, ICP increased in all but one patient when changing from supine position to lateral recumbent position (n = 15, median increase of 6.9 mmHg, IQR 3.1 to 9.9). Straightening the hips alone decreased ICP with 0.2 mmHg (n = 15, IQR - 0.5 to 2.0), while straightening the neck alone decreased ICP by 4.0 mmHg (n = 15, IQR - 5.9 to - 1.7). However, when straightening the hip and neck simultaneously ICP decreased by 6.4 mmHg (n = 6, IQR - 9.5 to - 4.4).Neck flexion alone, and neck flexion and hip flexion in combination, has significant confounding influence on ICP. This may cause patients to shift from a normal ICP range to a pathological ICP range, which will potentially affect treatment decisions. Consensus on guidelines for body position including neck and hip flexion measuring CSF

Background: Hydrocephalus requiring external ventricular drainage is common following aneurysmal subarachnoid hemorrhage (aSAH). Timing and strategy for the discontinuation of the external ventricular drain (EVD) are, however, controversial as guidelines are based on limited scientific evidence. A recent similar survey showed that guidelines and recommendations are not being followed. We conducted a questionnaire survey regarding the management of EVD treatment in patients with aSAH and investigated current treatment practice, consensus, and adherence to guidelines within the neurosurgical departments in Scandinavia. Methods: A questionnaire concerning the management of EVD discontinuation in patients with hydrocephalus following aSAH was distributed to all 14 neurosurgical departments in Scandinavia (Norway, Sweden, and Denmark). Neurosurgeons and neurosurgical trainees at all levels were asked to complete the questionnaire individually. A total of 175 completed questionnaires were received between May 2018 and April 2019, resulting in a response rate of 64 %. Results: Eighty-five percent of respondents reported no knowledge of international guidelines regarding EVD discontinuation in patients with hydrocephalus following aSAH. Within every department, respondents disagreed on whether a common discontinuation strategy was followed or not. Seventy-four percent decided upon the EVD discontinuation strategy mainly determined by patients’ clinical condition and drainage volume. Forty-five percent considered Glasgow Coma Score (GCS) the most important clinical variable when assessing the timing of EVD discontinuation. There was general agreement towards the initiation of EVD discontinuation 4–7 days after ictus of aSAH in a stable patient with a drainage volume of < 150 ml/day and intracranial pressure (ICP) < 15 mmHg. Conclusion: Awareness of and adherence to international guidelines regarding EVD discontinuation in patients with hydrocephalus following aSAH were limited in Scandinavia. Internal consensus at department level was absent. Initiation of the discontinuation process appeared to be case dependent and mainly influenced by the patients’ clinical condition and drainage volume. GCS was the clinical variable considered most important when deciding on the initiation of EVD discontinuation.

ObjectivesTo summarise the evidence on benefits and harms of prompt closure versus gradual weaning of external ventricular drainage (EVD) in patients with hydrocephalus following aneurysmal subarachnoid haemorrhage (aSAH) based on randomised clinical trials (RCTs) in humans.SettingRCTs comparing prompt closure versus gradual weaning of EVD in adult patients with hydrocephalus following aSAH were included.ParticipantsPatients aged equal to or greater than 18 years with an EVD due to hydrocephalus following aSAH were eligible for inclusion.Primary and secondary outcome measuresPrimary outcomes were all-cause mortality, any serious adverse event, rate of ventriculoperitoneal (VP) shunt placement and quality of life. Secondary outcomes were patients with shunt failure, hospital and neuro intensive care unit (NICU) length of stay (LOS) and complications related to treatment with an EVD. Data permitted report of rate of VP shunt placement, and hospital and NICU LOS.ResultsSix studies were assessed in full text. One RCT with 81 patients was included. Rate of VP shunt placement was 63.4% in the rapid weaning group (ie, prompt closure of the EVD; 41 patients) and 62.5% in the gradual weaning group (40 patients; p=0.932). LOS in hospital and NICU was significantly shorter in the rapidly weaned group compared with the gradually weaned group (mean 19.1 vs 21.5 days in hospital (p=0.03); and mean 14.1 vs 16.9 days in NICU (p=0.0002)). Data were insufficient to conduct meta-analysis, trial sequential analysis or subgroup analysis of heterogeneity and sensitivity. One RCT is currently ongoing.ConclusionsWe found insufficient evidence to favour any of the two strategies for EVD discontinuation in patients with hydrocephalus following aSAH.PROSPERO registration numberCRD42018108801.

KEY POINTS: During long‐term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension. Weightlessness prevents the normal cerebral volume and pressure ‘unloading’ associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology. By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments. Application of incremental LBNP demonstrated a non‐linear dose–response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure. This non‐invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension. ABSTRACT: Patients with elevated intracranial pressure (ICP) exhibit neuro‐ocular symptoms including headache, papilloedema and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space‐flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: six ambulatory neurosurgical patients with parenchymal ICP‐sensors and four former cancer patients with Ommaya‐reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head‐down tilt. LBNP from 0 to 50 mmHg at increments of 10 mmHg lowered ICP in a non‐linear dose‐dependent fashion; when supine (n = 10), ICP was decreased from 15 ± 2 mmHg to 14 ± 4, 12 ± 5, 11 ± 4, 10 ± 3 and 9 ± 4 mmHg, respectively (P