Automated detection of fatal cerebral haemorrhage in postmortem CT data.

During the last years, the detection of different causes of death based on postmortem imaging findings became more and more relevant. Especially postmortem computed tomography (PMCT) as a non-invasive, relatively cheap, and fast technique is progressively used as an important imaging tool for supporting autopsies. Additionally, previous works showed that deep learning applications yielded robust results for in vivo medical imaging interpretation. In this work, we propose a pipeline to identify fatal cerebral haemorrhage on three-dimensional PMCT data. We retrospectively selected 81 PMCT cases from the database of our institute, whereby 36 cases suffered from a fatal cerebral haemorrhage as confirmed by autopsy. The remaining 45 cases were considered as neurologically healthy. Based on these datasets, six machine learning classifiers (k-nearest neighbour, Gaussian naive Bayes, logistic regression, decision tree, linear discriminant analysis, and support vector machine) were executed and two deep learning models, namely a convolutional neural network (CNN) and a densely connected convolutional network (DenseNet), were trained. For all algorithms, 80% of the data was randomly selected for training and 20% for validation purposes and a five-fold cross-validation was executed. The best-performing classification algorithm for fatal cerebral haemorrhage was the artificial neural network CNN, which resulted in an accuracy of 0.94 for all folds. In the future, artificial neural network algorithms may be applied by forensic pathologists as a helpful computer-assisted diagnostics tool supporting PMCT-based evaluation of cause of death.

Cerebral haemorrhage in the patient with atrial fibrillation: do we employ the direct oral anticoagulants without waiting too long?

Intracranial haemorrhage (ICH) is the most feared haemorrhagic complication of oral anticoagulant therapy (OAT), although the risk is significantly lower with direct oral anticoagulants (DOACs) compared with warfarin. Intracranial haemorrhage is generally considered, by clinicians, to be an absolute contraindication to starting or resuming OAT in patients with atrial fibrillation (AF). On the other hand, the pivotal trials with DOACs excluded patients with previous ICH. Observational studies actually indicate a net clinical benefit in favour of DOAC in patients with AF and previous ICH. This benefit is confirmed by randomized clinical trials which, however, have the limitation of the small number of cases, but larger clinical trials comparing DOACs vs. aspirin or no therapy are underway. While OAT is certainly contraindicated in patients with lobar ICH and cerebral amyloid angiopathy, in other cases, the decision must be made in the individual patient through an accurate balance between thromboembolic risk and haemorrhagic risk and a multidisciplinary cardio-neurological evaluation.

Development and validation of a novel radiomics-clinical model for predicting post-stroke epilepsy after first-ever intracerebral haemorrhage.

OBJECTIVES: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. This study aimed to develop and validate a novel prediction model combining clinical factors and radiomics features to accurately identify patients at high risk of developing PSE after intracerebral haemorrhage (ICH). METHODS: Researchers performed a retrospective medical chart review to extract derivation and validation cohorts of patients with first-ever ICH that attended two tertiary hospitals in China between 2010 and 2020. Clinical data were extracted from electronic medical records and supplemented by tele-interview. Predictive clinical variables were selected by multivariable logistic regression to build the clinical model. Predictive radiomics features were identified, and a Rad-score was calculated according to the coefficient of the selected feature. Both clinical variables and radiomic features were combined to build the radiomics-clinical model. Performances of the clinical, Rad-score, and combined models were compared. RESULTS: A total of 1571 patients were included in the analysis. Cortical involvement, early seizures within 7 days of ICH, NIHSS score, and ICH volume were included in the clinical model. Rad-score, instead of ICH volume, was included in the combined model. The combined model exhibited better discrimination ability and achieved an overall better benefit against threshold probability than the clinical model in the decision curve analysis (DCA). CONCLUSIONS: The combined radiomics-clinical model was better able to predict ICH-associated PSE compared to the clinical model. This can help clinicians better predict an individual patient's risk of PSE following a first-ever ICH and facilitate earlier PSE diagnosis and treatment. KEY POINTS: • Radiomics has not been used in predicting the risk of developing PSE. • Higher Rad-scores were associated with higher risk of developing PSE. • The combined model showed better performance of PSE prediction ability.

Iatrogenic cerebral amyloid angiopathy: An illustrative case of a newly introduced disease.

BACKGROUND AND PURPOSE: Iatrogenic cerebral amyloid angiopathy (iCAA) is a specific type of cerebral amyloid angiopathy which is becoming increasingly diagnosed. It has been hypothesized that iCAA might arise as a late consequence of past neurosurgical interventions involving dural patch grafts. Positron emission tomography (PET) scans with amyloid tracers and the assay of beta-amyloid levels in cerebrospinal fluid (CSF) are auxiliary criteria, however, definite diagnosis remains histopathologically determined. METHODS: Case report. RESULTS: We present a 48-year-old patient who suffered multiple lobar cerebral haemorrhages from the age of 47. The patient had undergone surgery for remolval of hemangioblastoma with lyophilized dural graft at the age of 11, in 1987. Brain MRI, amiloid PET and CSF analysis led to a diagnosis of probable iCAA. CONCLUSION: It is necessary to increase the awareness of iCAA, in order to avoid overlooking the potential causal involvement of surgical procedures which took place far back in time. Moreover, the diagnostic relevance of amyloid PET and beta-amyloid levels in CSF must be emphasised.

Cycling-related cranio-spinal injuries admitted to a Major Trauma Centre in the cycling capital of the UK.

BACKGROUND: The increased popularity of cycling is leading to an anticipated increase in cycling-related traffic accidents and a need to better understand the demographics and epidemiology of craniospinal injuries in this vulnerable road user group. This study aims to systematically investigate and characterise cycling-related head and spine injuries seen in the Major Trauma Centre for the Eastern region, which has the highest cycling rates in the UK. METHODS: We performed a retrospective cohort study comparing the incidence, patterns, and severity of head and spine injuries in pedal cyclists presenting to the Major Trauma Centre in Cambridge between January 2012 and December 2020. Comparisons of injury patterns, characteristics, and associations were made according to mechanism of injury, helmet use, patient age and gender. RESULTS: A total of 851 patients were admitted after being involved in cycling-related collisions over the study period, with 454 (53%) sustaining head or spine injuries. The majority of victims (80%) were male and in mid-adulthood (median age 46 years). Head injuries were more common than spine injuries, with the most common head injuries being intracranial bleeds (29%), followed by skull fractures (12%), and cerebral contusions (10%). The most common spine injuries were cervical segment fractures, particularly C6 (9%), C7 (9%), and C2 (8%). Motorised collisions had a higher prevalence of spine fractures at each segment (p < 0.001) and were associated with a higher proportion of multi-vertebral fractures (p < 0.001). These collisions were also associated with impaired consciousness at the scene and more severe systemic injuries, including a lower Glasgow coma scale (R = -0.23, p < 0.001), higher injury severity score (R = 0.24, p < 0.001), and longer length of stay (R = 0.21, p < 0.001). Helmet use data showed that lack of head protection was associated with more severe injuries and poorer outcomes. CONCLUSION: As cycling rates continue to increase, healthcare providers may expect to see an increase in bicycle-related injuries in their practice. The insights gained from this study can inform the treatment of these injuries while highlighting the need for future initiatives aimed at increasing road safety and accident prevention.

Study of 851 cycling-related trauma patients in Cambridge, UK, shows high rates of head & spine injuries.Motorised collisions were associated with more severe injuries and impaired consciousness at the scene.The lack of helmet use was linked to more severe head injuries and impaired consciousness, but not to a longer hospital stay.Rising cycling rates may lead to increased incidence of these injuries in clinical practice.Our findings may be relevant for clinicians treating cycling-related traumatic injuries to head and spine.

External validation of brain arteriovenous malformation haemorrhage scores, AVICH, ICH and R2eD.

PURPOSE: To externally validate the arteriovenous malformation-related intracerebral haemorrhage (AVICH), intracerebral haemorrhage (ICH), and novel haemorrhage presentation risk score (R2eD) in brain arteriovenous malformations. METHODS: Adult patients diagnosed radiologically with an arteriovenous malformation (AVM) at a tertiary neurosurgical centre between 2007 and 2018 were eligible for inclusion. Both the AVICH and ICH scores were calculated for AVM-related symptomatic haemorrhage (SH) and compared against the modified Rankin scale (mRS) at discharge and last follow-up, with unfavourable outcome defined as mRS > 2. R2eD scores were stratified based on presentation with SH. External validity was assessed using Harrel's C-statistic. RESULTS: Two hundred fifty patients were included. Mean age at diagnosis was 46.2 years [SD = 16.5]). Eighty-seven patients (34.8%) had a SH, with 83 included in the analysis. Unfavourable mRS outcome was seen in 18 (21.6%) patients at discharge and 18 (21.6%) patients at last follow-up. The AVICH score C-statistic was 0.67 (95% confidence interval [CI], 0.53-0.80) at discharge and 0.70 (95% CI, 0.56-0.84) at last follow-up. The ICH score C-statistic was 0.78 (95% CI 0.67-0.88), at discharge and 0.80 (95% CI 0.69-0.91) at last follow-up. The R2eD score C-statistic for predicting AVM haemorrhage was 0.60 (95% CI, 0.53-0.67). CONCLUSIONS: The AVICH score showed fair-poor performance, while the ICH score showed good-fair performance. The R2eD score demonstrated poor performance, and its clinical utility in predicting AVM haemorrhage remains unclear.

A proposed novel traumatic brain injury classification system - an overview and inter-rater reliability validation on behalf of the Society of British Neurological Surgeons.

INTRODUCTION: The measurement of traumatic brain injury (TBI) 'severity' has traditionally been based on the earliest Glasgow Coma Score (GCS) recorded, however, the underlying parenchymal pathology is highly heterogonous. This heterogeneity renders prediction of outcome on an individual patient level inaccurate and makes comparison between patients both in clinical practice and research difficult. The complexity of this heterogeneity has resulted in generic all encompassing 'traumatic brain injury protocols'. Early management and studies of neuro-protectants are often done irrespective of TBI type, yet it may well be that a specific treatment may be beneficial in a subset of TBI pathologies. METHODS: A simple CT-based classification system rating the recognised types of blunt TBI (extradural, subdural, subarachnoid haemorrhage, contusions/intracerebral haematoma and diffuse axonal injury) as mild (1), moderate (2) or severe (3) is proposed. Hypoxic brain injury, a common secondary injury following TBI, is also included. Scores can be combined to reflect concomitant types of TBI and predominant location of injury is also recorded. To assess interrater reliability, 50 patient CT images were assessed by 5 independent clinicians of varying experience. Interrater reliability was calculated using overall agreement through Cronbach's alpha including confidence intervals for intra-class coefficients. RESULTS: Interrater reliability scores showed strong agreement for same score and same injury for TBIs with blood on CT and Cronbach's alpha co-efficient (range 0.87-0.93) demonstrated excellent correlation between raters. Cronbach's alpha was not affected when individual raters were removed. CONCLUSIONS: The proposed simple CT classification system has good inter-rater reliability and hence potentially could enable better individual prognostication and targeted treatments to be compared while also accounting for multiple intracranial injury types. Further studies are proposed and underway.

Insights in the pathophysiology of haemorrhagic strokes in a sub-Sahara African country, an epidemiological and MRI study.

OBJECTIVE: Intra-cerebral Haemorrhage (ICH) seems more prevalent in sub-Saharan Africa (SSA) than in High-Income Countries (HIC) with poorer clinical outcome. Higher impact of hypertension and/or amyloid angiopathy could account for this disproportion. Here, we sought to (i) retrospectively compare ICH clinical and imaging patterns in Belgium and Guinea and in a subsequent cohort (ii) prospectively compare brain MRI characteristics to seek evidence for a different proportion of amyloid angiopathy patterns. METHODS: Ninety one consecutive patients admitted for spontaneous ICH at Brussels Erasme-ULB Hospital and at Conakry Ignace Deen-UGANC were retrospectively compared in terms of ICH volume estimated with the ABC/2 method, clinical characteristics and modified ranking (mRS) score at 30 days. mRS was dichotomised as good outcomes (≤3) and poor outcomes (>3). A prospective cohort of 30 consecutive patients with ICH admitted at CHU Conakry Ignace Deen-UGANC was prospectively included to undergo brain MRI. Results of the Guinean MRI were compared to 30 patients randomly selected from Brussels' initial cohort. Paired Student's t-test and Mann-Whitney u-test were used for group comparisons. RESULTS: Age of ICH onset was higher in Belgium (68 ± 17 years vs. 56 ± 14 years, P < 0.01) while ICH volume and 30-day mortality rate were higher in Guinea (20 ml vs. 11 ml, P < 0.01 and mortality 33% vs. 10 %, P < 0.01). ICH burden in survivors in Conakry and Brussels showed respectively good outcomes in 56.7% and 60.4% (P = 0.09) and poor outcomes in 10.3% vs. 29.6% (P < 0.001). MRI analysis of the prospective cohort failed to disclose significant differences regarding brain MRI characteristics. CONCLUSIONS: Intra-cerebral Haemorrhage affected patients 15 years younger in Guinea with larger haematoma volumes and higher mortality than in Belgium. MRI findings did not show more prevalent amyloid angiopathy pathology suggesting that better primary prevention of hypertension could positively impact ICH epidemiology in Guinea.

OBJECTIF: L'hémorragie intracérébrale (HIC) semble plus répandue en Afrique subsaharienne (ASS) que dans les pays à revenu élevé (PRE), avec des résultats cliniques moins bons. Un impact plus élevé de l'hypertension et/ou de l'angiopathie amyloïde pourrait expliquer cette disproportion. Ici, nous avons cherché à (i) comparer rétrospectivement les schémas cliniques et d'imagerie de l'HIC en Belgique et en Guinée et dans une cohorte subséquente (ii) comparer de manière prospective les caractéristiques de l'IRM cérébrale pour rechercher des preuves d'une proportion différente des profils d'angiopathie amyloïde. MÉTHODES: 91 patients consécutifs admis pour HIC spontanée à l'hôpital Erasme-ULB de Bruxelles et à Ignace Deen-UGANC de Conakry ont été rétrospectivement comparés en termes de volume d'HIC estimé avec la méthode ABC/2, les caractéristiques cliniques et le score de classement modifié (mRS) à 30 jours. Le mRS a été dichotomisé en bons résultats (≤3) et mauvais résultats (>3). Une cohorte prospective de 30 patients consécutifs atteints d'HIC admis au CHU Ignace Deen-UGANC de Conakry a été incluse de manière prospective pour subir une IRM cérébrale. Les résultats de l'IRM guinéenne ont été comparés à ceux de 30 patients sélectionnés aléatoirement dans la cohorte initiale de Bruxelles. Le test t de Student apparié et le test u de Mann-Whitney ont été utilisés pour les comparaisons de groupe. RÉSULTATS: L'âge d'apparition de l'HIC était plus élevé en Belgique (68 ± 17 ans vs 56 ± 14 ans, P < 0,01) tandis que le volume de l'HIC et le taux de mortalité à 30 jours étaient plus élevés en Guinée (20 ml vs 11 ml, P < 0,01 et mortalité 33% vs 10%, P <0,01). La charge de l'HIC chez les survivants à Conakry et à Bruxelles a montré respectivement de bons résultats dans 56,7% et 60,4% (P = 0,09) et de mauvais résultats dans 10,3% vs 29,6% (P < 0,001). L'analyse IRM de la cohorte prospective n'a pas permis de révéler de différences significatives concernant les caractéristiques de l'IRM cérébrale. CONCLUSIONS: L'HIC a touché des patients 15 ans plus jeunes en Guinée avec des volumes d'hématomes plus importants et une mortalité plus élevée qu'en Belgique. Les résultats de l'IRM n'ont pas montré de pathologie angiopathique amyloïde plus répandue, ce qui suggère qu'une meilleure prévention primaire de l'hypertension pourrait avoir un impact positif sur l'épidémiologie de l'HIC en Guinée.

A model comprising the blend sign and black hole sign shows good performance for predicting early intracerebral haemorrhage expansion: a comprehensive evaluation of CT features.

OBJECTIVE: To predict early intracerebral haemorrhage expansion (HE) by comprehensive evaluation of commonly used noncontrast computed tomography (NCCT) features. METHODS: Two hundred eighty-eight patients who had a spontaneous intracerebral haemorrhage (ICH) were included. All of the patients had undergone baseline NCCT within 6 h after ICH symptom onset. Ten NCCT features were extracted. Univariate analysis and multivariable logistic regression analysis were used to select the features. Using the finally selected features, a logistic regression model was built with a training cohort (n = 202) and subsequently validated in an independent test cohort (n = 86). Additionally, stratification analysis was performed in cases with and without anticoagulant therapy. RESULTS: HE was found in 78 patients (27.1%). The blend sign and black hole sign were finally selected. The logistic regression model built with the two features exhibited accuracies of 76.7% and 75.6%, specificities of 98.6% and 98.4%, and positive predictive values (PPVs) of 83.3% and 75.0% for the training and test cohorts, respectively. The model also showed specificities of 100% and 98.5% and PPVs of 100% and 76.9% for the anticoagulant and non-anticoagulant drug use groups, respectively. These performances were better than those of each of the separate features. CONCLUSIONS: By comprehensive evaluation, the model comprising the blend sign and black hole sign showed good performance for predicting early intracerebral haemorrhage expansion, particularly for high specificity and PPV, regardless of the anticoagulant status. KEY POINTS: • Early identification of patients who are more likely to have haematoma expansion is important for therapeutic intervention. • Many radiological features have been reported to correlate with intracerebral haemorrhage expansion. • By integrating only the blend sign and black hole sign, the logistic regression model showed good performance for predicting early intracerebral haemorrhage expansion.

Alemtuzumab in multiple sclerosis: A retrospective analysis of occult hemorrhagic magnetic resonance imaging lesions and risk factors.

BACKGROUND AND PURPOSE: Alemtuzumab, a monoclonal CD52 antibody, is a high-efficacy disease-modifying-therapy in relapsing-remitting multiple sclerosis (RRMS). Recently, intracerebral hemorrhage (ICH) was reported as a possible treatment-related adverse event. Arterial hypertension during infusion was suggested as a potential cause, although platelet or endothelial dysfunction may also contribute. This study aimed to screen for occult hemorrhagic cerebral lesions after alemtuzumab treatment and to further elucidate risk factors. METHODS: We included 30 RRMS patients who received alemtuzumab treatment at Ghent University Hospital or Sint-Jan Bruges Hospital. Retrospective data concerning vital signs, adverse effects and thrombocyte levels during treatment were collected. The occurrence of occult intracranial hemorrhagic lesions was assessed by magnetic resonance imaging with susceptibility-weighted imaging (SWI). RESULTS: The mean (standard deviation [SD]) systolic blood pressure (SBP) during the morning, afternoon and evening was 120 (3.38) mmHg during first administration and 114 (4.40) mmHg during second administration (N = 13). There was no significant increase in SBP when comparing morning, afternoon and evening per day, nor was there a significant difference in daily mean SBP between consecutive administration days. Thrombocyte count during treatment cycles ranged between 107 × 109 /L and 398 × 109 /L, with a mean (SD) absolute reduction of 59.3 × 109 /L (50.65) or a mean (SD) relative reduction of 25.0 (12.84)% (N = 20). No patient had ICH, nor did SWI show any cerebral microbleeds or other hemorrhagic lesions post-treatment (N = 23). CONCLUSIONS: In our patient population, alemtuzumab treatment was not associated with arterial hypertension, ICH or occult microbleeds. Possible differences in administration regimen (ambulatory vs. in-hospital setting) and patient population (cardiovascular risk) might explain an increased risk in different populations.

Causality assessment between reported fatal cerebral haemorrhage and suspected drugs: developing a new algorithm based on the analysis of the Japanese Adverse Event Report (JADER) database and literature review.

PURPOSE: Cerebral haemorrhage is a life-threatening event with various causes including adverse drug reactions (ADRs). Several methods have been proposed for the causality assessment of ADRs, but none specific for cerebral haemorrhage. The purpose of this study was to develop an algorithm for causality assessment between drugs and fatal cerebral haemorrhage, based on the analysis of data from the Japanese Adverse Drug Event Report (JADER) database and literature review. METHODS: All fatal ADRs reported in the JADER database between April 2004 and March 2020 were searched, and literature on drug-related cerebral haemorrhage or general causality assessment was reviewed to summarise the information on causality between cerebral haemorrhage and ADRs. RESULTS: Of the 50,095 cases identified in the JADER database, cerebral haemorrhage was the fifth most reported cause of fatal ADRs, but the causality of >80% of the events was published as 'Unassessable'. The literature review identified articles on drug-related cerebral haemorrhage and causality assessment methods in general. Based on these articles, information on five categories (temporal relationship, previous knowledge about the relationship between drug action and ADRs, alternative aetiological candidate, appropriateness of drug use, and the relationship between death and ADRs) was determined for causality assessment between a suspected drug and fatal cerebral haemorrhage; a new algorithm was created using this information. CONCLUSION: In this study, the information considered necessary for causality assessment between drugs and fatal cerebral haemorrhage was reviewed and an assessment algorithm was developed. Future studies are needed to validate the usefulness of this method.

Intraventricular hemorrhage as clinical presentation of herpes simplex virus encephalitis. A case report and review of the literature.

OBJECTIVE: Herpes simplex virus encephalitis (HSVE) represents the most common cause of sporadic encephalitis in humans. The development of intracerebral hematomas is rare and late during the course of HSVE. To report a case of a patient with HSVE who initially presented a diffuse intracranial hemorrhage with predominant intraventricular bleeding. CASE REPORT: A 66-year-old man was admitted to the Emergency Department with acute headache. Antecedents: alcohol consumption and ethylic hepatopathy. The brain computed tomography showed acute tetraventricular hemorrhage and hydrocephalus. The blood analysis showed pancytopenia and alteration of all hepatic parameters. After external drainage of cerebrospinal fluid the patient presented a worsening of headache, disorientation, mild left hemiparesis, neck stiffness and temperature of 37.6 °C. The cerebrospinal fluid was hemorrhagic, with 3 lymphocytes/mm3, 60 mg/dL of proteins and PCR positive for Herpes simplex virus type 1. The patient improved with intravenous acyclovir, however he experienced several medical complications which caused his dead. DISCUSSION: The patient presented an atypical cerebral bleeding related to HSVE because the development of hematoma was early and the topography of hemorrhage was basically intraventricular. Probably, both atypical characteristics were related to thrombocytopenia and severe coagulation disorder. This case expands the spectrum of cerebrovascular disorders associated with HSVE.

Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation.

Plasma amyloid-beta (Aß) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aß alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aß measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3-4 years later (NC = 8; MC = 9). Plasma Aß1-40 and Aß1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aß1-40: p = 0.001; Aß1-42: p = 0.0004) and T2 (Aß1-40: p = 0.001; Aß1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aß1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aß1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aß may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required.

Recent silent infarcts do not increase the risk of haemorrhage after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Haemorrhagic transformation (HT) is one of the main risks of intravenous thrombolysis (IVT) for acute ischaemic stroke. Contraindications serve to exclude patients at high risk of HT after IVT. One of these contraindications is a stroke within the preceding 3 months. It is unclear if this contraindication should include recent clinically silent infarcts (RSIs). The aim of this study was to investigate whether RSIs are associated with a higher risk of HT and a worse clinical outcome after IVT for acute ischaemic stroke. METHODS: In a retrospective monocentric cohort study, all patients who received IVT for acute ischaemic stroke based on magnetic resonance imaging were assessed over 5 years. RSIs were defined as lesions with diffusion restriction and positive signal on fluid attenuated inversion recovery sequences. Patients with RSIs (RSI+) were compared to patients without RSIs (RSI-) regarding HT after IVT and clinical outcome. RESULTS: In all, 981 patients who had received IVT for acute ischaemic stroke demonstrated by magnetic resonance imaging were identified. RSIs were detected in 115 patients (11.5%). HT after IVT was observed in 32 (28.3%) RSI+ and 56 (25.8%) RSI- patients (P = 0.624). Symptomatic intracerebral haemorrhage was noted in two (1.8%) RSI+ and five (2.3%) RSI- patients (P = 1.000). No differences in clinical outcome were observed. CONCLUSIONS: The detection of RSIs in patients treated with IVT for acute ischaemic stroke was not associated with a higher risk of HT or a worse clinical outcome. The results of this study argue against considering RSIs as a contraindication for IVT.

Fatal intracranial haemorrhage occurring after oral anticoagulant treatment initiation for secondary stroke prevention in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: In this pooled analysis of seven multicentre cohorts potential differences were investigated in the incidence, characteristics and outcomes between intracranial haemorrhages (ICHs) associated with the use of non-vitamin K antagonist oral anticoagulants (NOAC-ICH) or with vitamin K antagonists (VKA-ICH) in ischaemic stroke patients after oral anticoagulant treatment initiation for atrial fibrillation (AF). METHODS: Data from 4912 eligible AF patients who were admitted in a stroke unit with ischaemic stroke or transient ischaemic attack and who were treated with either VKAs or NOACs within 3 months post-stroke were included. Fatal ICH was defined as death occurring during the first 30 days after ICH onset. A meta-analysis of available observational studies reporting 30-day mortality rates from NOAC-ICH or VKA-ICH onset was additionally performed. RESULTS: During 5970 patient-years of follow-up 71 participants had an ICH, of whom 20 were NOAC-ICH and 51 VKA-ICH. Patients in the two groups had comparable baseline characteristics, except for the higher prevalence of kidney disease in VKA-ICH patients. There was a non-significant higher number of fatal ICH in patients with VKAs (11 events per 3385 patient-years) than in those with NOACs (three events per 2623 patient-years; hazard ratio 0.32, 95% confidence interval 0.09-1.14). Three-month functional outcomes were similar (P > 0.2) in the two groups. The meta-analysis showed a lower 30-day mortality risk for patients with NOAC-ICH compared to VKA-ICH (relative risk 0.70, 95% confidence interval 0.51-0.95). CONCLUSIONS: Non-vitamin K oral anticoagulants for intracranial haemorrhages and VKA-ICH occurring during secondary stroke prevention of AF patients have comparable baseline characteristics and outcomes except for the risk of fatal ICH within 30 days, which might be greater in VKA-ICH.

What clinical practice strategies have been shown to decrease incidence rates of intraventricular haemorrhage in preterm infants?

AIM: To answer the clinical question 'In infants about to be delivered and admitted to neonatal units, what clinical practice strategies, compared to standard care, have been shown to decrease incidence rates of intraventricular haemorrhage (IVH)?' METHODS: MEDLINE via Ovid (1943 to 5 January 2018), Embase via Ovid (1974 to 5 January 2018) and the Cochrane Library (5 January 2018) were searched for relevant articles. RESULTS: A total of 478 articles, after the removal of duplicates, were found and screened by title and abstract. Forty full-text articles were subsequently reviewed, and 19 were included as relevant to the structured clinical question. An additional article was included based on expert advice. CONCLUSION: There are various levels of research evidence for clinical practice strategies to decrease the incidence rates of IVH. Higher-quality evidence suggests that antenatal corticosteroids decrease the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit are associated with decreased rates of IVH.

The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs.

Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVCSal, n = 4; UVCBM, n = 6) were humanely killed without intervention; ventilated lambs (VentSal, n = 5; VentBM, n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVCBM than in UVCSal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in -VentBM lambs (p < 0.05 vs. VentSal). In the subcortical WM, microglial infiltration was increased in the VentSal group compared to UVCSal. The proportion of activated microglia and protein extravasation was higher in the VentBM group compared to VentSal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the VentBM group compared to UVCSal, UVCBM, and VentSal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.

Prevalence of and risk factors for cerebral microbleeds among adult patients with haemophilia A or B.

INTRODUCTION: Cerebral microbleeds (CMBs) represent clinically silent haemorrhagic events. Cerebral microbleeds (CMBs) portend negative neurovascular and cognitive outcomes in the general population and are associated with cognitive impairment in persons with haemophilia (PWH). Prevalence, patterns, and risk factors for CMBs in PWH have not been directly compared to persons without coagulopathy. AIM: To examine prevalence, patterns, and risk factors for CMBs in PWH vs normal controls. METHODS: Adults with haemophilia A or B and haemostatically normal controls were recruited. Subjects were excluded if taking an antithrombotic agent other than low-dose aspirin (<100 mg). All subjects underwent T2*MRI of the brain; scans were reviewed independently by two neuroradiologists blinded to subject group to determine the presence of CMBs. RESULTS: We recruited 31 PWH and 32 controls. Human immunodeficiency virus (HIV) and history of hepatitis C virus (HCV) infection were more prevalent in PWH; smoking was more common among controls. Cardiovascular (CV) risk factors were similar between groups. Prevalence of CMBs was 35% in PWH and 25% in controls (P = .42). Among PWH, advanced age, history of HCV infection, and CV risk factors were associated with CMBs. Multiple and large (>5 mm) CMBs were seen only in PWH. CONCLUSIONS: Cerebral microbleeds (CMBs) are common in adults with haemophilia, but not clearly more prevalent than in haemostatically normal controls. In PWH, older age, HCV infection, CV risk factors, and the presence of an inhibitor were associated with CMBs. Large CMBs and multiple CMBs may be more prevalent in PWH than in the general population. The clinical impact of CMBs in PWH requires further study.

Iodine concentration: a new, important characteristic of the spot sign that predicts haematoma expansion.

OBJECTIVES: The computed tomography angiography (CTA) spot sign is a validated predictor of haematoma expansion (HE) in spontaneous intracerebral haemorrhage (SICH). We investigated whether defining the iodine concentration (IC) inside the spot sign and the haematoma on Gemstone spectral imaging (GSI) would improve its sensitivity and specificity for predicting HE. METHODS: From 2014 to 2016, we prospectively enrolled 65 SICH patients who underwent single-phase spectral CTA within 6 h. Logistic regression was performed to assess the risk factors for HE. The predictive performance of individual spot sign characteristics was examined via receiver operating characteristic (ROC) analysis. RESULTS: The spot sign was detected in 46.1% (30/65) of patients. ROC analysis indicated that IC inside the spot sign had the greatest area under the ROC curve for HE (0.858; 95% confidence interval, 0.727-0.989; p = 0.003). Multivariate analysis found that spot sign with higher IC (i.e. IC > 7.82 100 µg/ml) was an independent predictor of HE (odds ratio = 34.27; 95% confidence interval, 5.608-209.41; p < 0.001) with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 0.81, 0.75, 0.90 and 0.60, respectively; while the spot sign showed sensitivity, specificity, PPV and NPV of 0.81, 0.79, 0.73 and 0.86. Logistic regression analysis indicated that the IC in haematomas was independently associated with HE (odds ratio = 1.525; 95% confidence interval, 1.041-2.235; p = 0.030). CONCLUSIONS: ICs in haematoma and in spot sign were all independently associated with HE. IC analysis in spectral imaging may help to identify SICH patients for targeted haemostatic therapy. KEY POINTS: • Iodine concentration in spot sign and haematoma can predict haematoma expansion • Spectral imaging could measure the IC inside the spot sign and haematoma • IC in spot sign improved the positive predictive value (PPV) cf. CTA.

Acute intraparenchymal cerebral haemorrhage in an Iberian golden eagle - a case report.

BACKGROUND: In birds there are reports of intracranial lesions but not of the clinical, computed tomographic and histopathologic features of acute intraparenchymal cerebral haemorrhage in Iberian golden eagle. CASE PRESENTATION: The following report describes a case of a 30-year-old Iberian golden eagle (Aquila chrysaetos homeyeri) with no history of trauma, presented with acute opisthotonus, left head tilt and circling, anisocoria, positional nystagmus, and ataxia. The main differential diagnosis were hypovitaminosis B or E and intracranial disease due to trauma, infection, toxins or masses. A computed tomography (CT) of the head was performed with an 8-slices scanner and evidenced a hyperdense (63-65 HU) non-enhancing homogeneous well delineated round area in the midbrain, with 6 mm in its highest diameter. The attenuation values and the non-enhancing nature of the lesion strongly suggested the diagnosis of acute intraparenchymal haemorrhage, which was histologically confirmed after necropsy. CONCLUSIONS: In birds with a central neurological dysfunction, the diagnosis of acute brain haemorrhage should be considered when the CT evidences a non-enhancing, homogeneous, well circumscribed hyperattenuated round area.