The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: An important proportion of patients with spontaneous intracerebral hemorrhage (ICH) undergo neurosurgical intervention to reduce mass effect from large hematomas and control the complications of bleeding, including hematoma expansion and hydrocephalus. The Tranexamic acid (TXA) for hyperacute primary IntraCerebral Hemorrhage (TICH-2) trial demonstrated that tranexamic acid (TXA) reduces the risk of hematoma expansion. We hypothesized that TXA would reduce the frequency of surgery (primary outcome) and improve functional outcome at 90 days in surgically treated patients in the TICH-2 data set. METHODS: Participants enrolled in TICH-2 were randomized to placebo or TXA. Participants randomized to either TXA or placebo were analyzed for whether they received neurosurgery within 7 days and their characteristics, outcomes, hematoma volumes (HVs) were compared. Characteristics and outcomes of participants who received surgery were also compared with those who did not. RESULTS: Neurosurgery was performed in 5.2% of participants (121/2325), including craniotomy (57%), hematoma drainage (33%), and external ventricular drainage (21%). The number of patients receiving surgery who received TXA vs placebo were similar at 4.9% (57/1153) and 5.5% (64/1163), respectively (odds ratio [OR] 0.893; 95% CI 0.619-1.289; P-value = .545). TXA did not improve outcome compared with placebo in either surgically treated participants (OR 0.79; 95% CI 0.30-2.09; P = .64) or those undergoing hematoma evacuation by drainage or craniotomy (OR 1.19 95% 0.51-2.78; P-value = .69). Postoperative HV was not reduced by TXA (mean difference -8.97 95% CI -23.77, 5.82; P-value = .45). CONCLUSION: TXA was not associated with less neurosurgical intervention, reduced HV, or improved outcomes after surgery.

Safety and efficacy of adjunctive intra-arterial antithrombotic therapy during endovascular thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Half of patients who achieve successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke experience poor functional outcome. We aim to investigate whether the use of adjunctive intra-arterial antithrombotic therapy (AAT) during EVT is safe and efficacious compared with standard therapy (ST) of EVT with or without prior intravenous thrombolysis. METHODS: Electronic databases were searched (PubMed/MEDLINE, Embase, Cochrane Library) from 2010 until October 2023. Data were pooled using a random-effects model and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using ROBINS-I and ROB-2. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes were successful recanalization (modified Thrombolysis In Cerebral Infarction (TICI) 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: 41 randomized and non-randomized studies met the eligibility criteria. Overall, 15 316 patients were included; 3296 patients were treated with AAT during EVT and 12 020 were treated with ST alone. Compared with ST, patients treated with AAT demonstrated higher odds of functional independence (46.5% AAT vs 42.6% ST; OR 1.22, 95% CI 1.07 to 1.40, P=0.004, I2=48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P<0.0001, I2=20%). The rates of sICH (OR 1.00, 95% CI 0.82 to 1.22,P=0.97, I2=13%) and successful recanalization (OR 1.09, 95% CI 0.84 to 1.42, P=0.52, I2=76%) were not significantly different. CONCLUSION: The use of AAT during EVT may improve functional outcomes and reduce mortality rates compared with ST alone, without an increased risk of sICH. These findings should be interpreted with caution pending the results from ongoing phase III trials to establish the efficacy and safety of AAT during EVT.

Metabolite profiles of medulloblastoma for rapid and non-invasive detection of molecular disease groups.

BACKGROUND: The malignant childhood brain tumour, medulloblastoma, is classified clinically into molecular groups which guide therapy. DNA-methylation profiling is the current classification 'gold-standard', typically delivered 3-4 weeks post-surgery. Pre-surgery non-invasive diagnostics thus offer significant potential to improve early diagnosis and clinical management. Here, we determine tumour metabolite profiles of the four medulloblastoma groups, assess their diagnostic utility using tumour tissue and potential for non-invasive diagnosis using in vivo magnetic resonance spectroscopy (MRS). METHODS: Metabolite profiles were acquired by high-resolution magic-angle spinning NMR spectroscopy (MAS) from 86 medulloblastomas (from 59 male and 27 female patients), previously classified by DNA-methylation array (WNT (n = 9), SHH (n = 22), Group3 (n = 21), Group4 (n = 34)); RNA-seq data was available for sixty. Unsupervised class-discovery was performed and a support vector machine (SVM) constructed to assess diagnostic performance. The SVM classifier was adapted to use only metabolites (n = 10) routinely quantified from in vivo MRS data, and re-tested. Glutamate was assessed as a predictor of overall survival. FINDINGS: Group-specific metabolite profiles were identified; tumours clustered with good concordance to their reference molecular group (93%). GABA was only detected in WNT, taurine was low in SHH and lipids were high in Group3. The tissue-based metabolite SVM classifier had a cross-validated accuracy of 89% (100% for WNT) and, adapted to use metabolites routinely quantified in vivo, gave a combined classification accuracy of 90% for SHH, Group3 and Group4. Glutamate predicted survival after incorporating known risk-factors (HR = 3.39, 95% CI 1.4-8.1, p = 0.025). INTERPRETATION: Tissue metabolite profiles characterise medulloblastoma molecular groups. Their combination with machine learning can aid rapid diagnosis from tissue and potentially in vivo. Specific metabolites provide important information; GABA identifying WNT and glutamate conferring poor prognosis. FUNDING: Children with Cancer UK, Cancer Research UK, Children's Cancer North and a Newcastle University PhD studentship.

CHIASM-Net: Artificial Intelligence-Based Direct Identification of Chiasmal Abnormalities in Albinism.

Purpose: Albinism is a congenital disorder affecting pigmentation levels, structure, and function of the visual system. The identification of anatomical changes typical for people with albinism (PWA), such as optic chiasm malformations, could become an important component of diagnostics. Here, we tested an application of convolutional neural networks (CNNs) for this purpose. Methods: We established and evaluated a CNN, referred to as CHIASM-Net, for the detection of chiasmal malformations from anatomic magnetic resonance (MR) images of the brain. CHIASM-Net, composed of encoding and classification modules, was developed using MR images of controls (n = 1708) and PWA (n = 32). Evaluation involved 8-fold cross validation involving accuracy, precision, recall, and F1-score metrics and was performed on a subset of controls and PWA samples excluded from the training. In addition to quantitative metrics, we used Explainable AI (XAI) methods that granted insights into factors driving the predictions of CHIASM-Net. Results: The results for the scenario indicated an accuracy of 85 ± 14%, precision of 90 ± 14% and recall of 81 ± 18%. XAI methods revealed that the predictions of CHIASM-Net are driven by optic-chiasm white matter and by the optic tracts. Conclusions: CHIASM-Net was demonstrated to use relevant regions of the optic chiasm for albinism detection from magnetic resonance imaging (MRI) brain anatomies. This indicates the strong potential of CNN-based approaches for visual pathway analysis and ultimately diagnostics.

Clinical features and imaging characteristics in achiasmia.

Achiasmia is a rare visual pathway maldevelopment with reduced decussation of the axons in the optic chiasm. Our aim was to investigate clinical characteristics, macular, optic nerve and brain morphology in achiasmia. A prospective, cross-sectional, observational study of 12 participants with achiasmia [8 males and 4 females; 29.6 ± 18.4 years (mean ± standard deviation)] and 24 gender-, age-, ethnicity- and refraction-matched healthy controls was done. Full ophthalmology assessment, eye movement recording, a high-resolution spectral-domain optical coherence tomography of the macular and optic disc, five-channel visual-evoked responses, eye movement recordings and MRI scans of the brain and orbits were acquired. Achiasmia was confirmed in all 12 clinical participants by visual-evoked responses. Visual acuity in this group was 0.63 ± 0.19 and 0.53 ± 0.19 for the right and left eyes, respectively; most participants had mild refractive errors. All participants with achiasmia had see-saw nystagmus and no measurable stereo vision. Strabismus and abnormal head position were noted in 58% of participants. Optical coherence tomography showed optic nerve hypoplasia with associated foveal hypoplasia in four participants. In the remaining achiasmia participants, macular changes with significantly thinner paracentral inner segment (P = 0.002), wider pit (P = 0.04) and visual flattening of the ellipsoid line were found. MRI demonstrated chiasmatic aplasia in 3/12 (25%), chiasmatic hypoplasia in 7/12 (58%) and a subjectively normal chiasm in 2/12 (17%). Septo-optic dysplasia and severe bilateral optic nerve hypoplasia were found in three patients with chiasmic aplasia/hypoplasia on MRI. In this largest series of achiasmia patients to date, we found for the first time that neuronal abnormalities occur already at the retinal level. Foveal changes, optic nerve hypoplasia and the midline brain anomaly suggest that these abnormalities could be part of the same spectrum, with different manifestations of events during foetal development occurring with varying severity.

Automated detection of cerebral microbleeds on MR images using knowledge distillation framework.

Introduction: Cerebral microbleeds (CMBs) are associated with white matter damage, and various neurodegenerative and cerebrovascular diseases. CMBs occur as small, circular hypointense lesions on T2*-weighted gradient recalled echo (GRE) and susceptibility-weighted imaging (SWI) images, and hyperintense on quantitative susceptibility mapping (QSM) images due to their paramagnetic nature. Accurate automated detection of CMBs would help to determine quantitative imaging biomarkers (e.g., CMB count) on large datasets. In this work, we propose a fully automated, deep learning-based, 3-step algorithm, using structural and anatomical properties of CMBs from any single input image modality (e.g., GRE/SWI/QSM) for their accurate detections. Methods: In our method, the first step consists of an initial candidate detection step that detects CMBs with high sensitivity. In the second step, candidate discrimination step is performed using a knowledge distillation framework, with a multi-tasking teacher network that guides the student network to classify CMB and non-CMB instances in an offline manner. Finally, a morphological clean-up step further reduces false positives using anatomical constraints. We used four datasets consisting of different modalities specified above, acquired using various protocols and with a variety of pathological and demographic characteristics. Results: On cross-validation within datasets, our method achieved a cluster-wise true positive rate (TPR) of over 90% with an average of <2 false positives per subject. The knowledge distillation framework improves the cluster-wise TPR of the student model by 15%. Our method is flexible in terms of the input modality and provides comparable cluster-wise TPR and better cluster-wise precision compared to existing state-of-the-art methods. When evaluating across different datasets, our method showed good generalizability with a cluster-wise TPR >80 % with different modalities. The python implementation of the proposed method is openly available.

Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes.

BACKGROUND: We aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes. METHODS: Clinical information and brain MRIs were collected from 221 healthy individuals and 823 people with MS at 8 MAGNIMS centres. The patients were divided into four clinical phenotypes: clinically isolated syndrome, relapsing-remitting, secondary progressive and primary progressive. Advanced tractography methods were used to obtain connectivity matrices. Then, differences in whole-brain and nodal graph-derived measures, and in the fractional anisotropy of connections between groups were analysed. Support vector machine algorithms were used to classify groups. RESULTS: Clinically isolated syndrome and relapsing-remitting patients shared similar network changes relative to controls. However, most global and local network properties differed in secondary progressive patients compared with the other groups, with lower fractional anisotropy in most connections. Primary progressive participants had fewer differences in global and local graph measures compared with clinically isolated syndrome and relapsing-remitting patients, and reductions in fractional anisotropy were only evident for a few connections. The accuracy of support vector machine to discriminate patients from healthy controls based on connection was 81%, and ranged between 64% and 74% in distinguishing among the clinical phenotypes. CONCLUSIONS: In conclusion, brain connectivity is disrupted in MS and has differential patterns according to the phenotype. Secondary progressive is associated with more widespread changes in connectivity. Additionally, classification tasks can distinguish between MS types, with subcortical connections being the most important factor.

Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: a secondary analysis of a large randomised controlled trial.

Background: Tranexamic acid reduced haematoma expansion and early death, but did not improve functional outcome in the tranexamic acid for hyperacute spontaneous intracerebral haemorrhage-2 (TICH-2) trial. In a predefined subgroup, there was a statistically significant interaction between prerandomisation baseline systolic blood pressure (SBP) and the effect of tranexamic acid on functional outcome (p=0.019). Methods: TICH-2 was an international prospective double-blind placebo-controlled randomised trial evaluating intravenous tranexamic acid in patients with acute spontaneous intracerebral haemorrhage (ICH). Prerandomisation baseline SBP was split into predefined ≤170 and >170 mm Hg groups. The primary outcome at day 90 was the modified Rankin Scale (mRS), a measure of dependency, analysed using ordinal logistic regression. Haematoma expansion was defined as an increase in haematoma volume of >33% or >6 mL from baseline to 24 hours. Data are OR or common OR (cOR) with 95% CIs, with significance at p<0.05. Results: Of 2325 participants in TICH-2, 1152 had baseline SBP≤170 mm Hg and were older, had larger lobar haematomas and were randomised later than 1173 with baseline SBP>170 mm Hg. Tranexamic acid was associated with a favourable shift in mRS at day 90 in those with baseline SBP≤170 mm Hg (cOR 0.73, 95% CI 0.59 to 0.91, p=0.005), but not in those with baseline SBP>170 mm Hg (cOR 1.05, 95% CI 0.85 to 1.30, p=0.63). In those with baseline SBP≤170 mm Hg, tranexamic acid reduced haematoma expansion (OR 0.62, 95% CI 0.47 to 0.82, p=0.001), but not in those with baseline SBP>170 mm Hg (OR 1.02, 95% CI 0.77 to 1.35, p=0.90). Conclusions: Tranexamic acid was associated with improved clinical and radiological outcomes in ICH patients with baseline SBP≤170 mm Hg. Further research is needed to establish whether certain subgroups may benefit from tranexamic acid in acute ICH. Trial registration number: ISRCTN93732214.

Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi-based consensus survey of international experts.

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.

Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial.

BACKGROUND: The risk of death from spontaneous intracerebral haemorrhage is increased for people taking antiplatelet drugs. We aimed to assess the feasibility of randomising patients on antiplatelet drug therapy with spontaneous intracerebral haemorrhage to desmopressin or placebo to reduce the antiplatelet drug effect. METHODS: DASH was a phase 2, randomised, placebo-controlled, multicentre feasibility trial. Patients were recruited from ten acute stroke centres in the UK and were eligible if they had an intracerebral haemorrhage with stroke symptom onset within 24 h of randomisation, were aged 18 years or older, and were taking an antiplatelet drug. Participants were randomly assigned (1:1) to a single dose of intravenous desmopressin 20 µg or matching placebo. Treatment allocation was concealed from all staff and patients involved in the trial. The primary outcome was feasibility, which was measured as the number of eligible patients randomised and the proportion of eligible patients approached, and analysis was by intention to treat. The trial was prospectively registered with ISRCTN (reference ISRCTN67038373), and it is closed to recruitment. FINDINGS: Between April 1, 2019, and March 31, 2022, 1380 potential participants were screened for eligibility. 176 (13%) participants were potentially eligible, of whom 57 (32%) were approached, and 54 (31%) consented and were subsequently recruited and randomly assigned to receive desmopressin (n=27) or placebo (n=27). The main reason for eligible patients not being recruited was the patient arriving out of hours (74 [61%] of 122 participants). The recruitment rate increased after the enrolment period was extended from 12 h to 24 h, but it was then impaired due to the COVID-19 pandemic. Of the 54 participants included in the analysis (mean age 76·4 years [SD 11·3]), most were male (36 [67%]) and White (50 [93%]). 53 (98%) of 54 participants received all of their allocated treatment (one participant assigned desmopressin only received part of the infusion). No participants were lost to follow-up or withdrew from the trial. Death or dependency on others for daily activities at day 90 (modified Rankin Scale score >4) occurred in six (22%) of 27 participants in the desmopressin group and ten (37%) of 27 participants in the placebo group. Serious adverse events occurred in 12 (44%) participants in the desmopressin group and 13 (48%) participants in the placebo group. The most common adverse events were expansion of the haemorrhagic stroke (four [15%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group) and pneumonia (one [4%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group). INTERPRETATION: Our results show it is feasible to randomise patients with spontaneous intracerebral haemorrhage who are taking antiplatelet drugs to desmopressin or placebo. Our findings support the need for a definitive trial to determine if desmopressin improves outcomes in patients with intracerebral haemorrhage on antiplatelet drug therapy. FUNDING: National Institute for Health Research.

Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): Study protocol for a multicentre randomised controlled trial.

BACKGROUND: Observational studies have demonstrated improved outcomes with the adjunctive use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) for anterior circulation acute ischaemic stroke (AIS). However, the lack of high-level evidence and global practice heterogeneity justifies a randomised controlled trial (RCT) to investigate the effect of transient proximal blood flow arrest on the procedural and clinical outcomes of patients with AIS following EVT. HYPOTHESIS: Proximal blood flow arrest in the cervical internal carotid artery during EVT for proximal large vessel occlusion is superior to no flow arrest in achieving complete vessel recanalisation. METHODS: ProFATE is an investigator-initiated, pragmatic, multicentre RCT with blinding of participants and outcome assessment. An estimated 124 participants with an anterior circulation AIS due to large vessel occlusion, an NIHSS of ⩾2, ASPECTS ⩾ 5 and eligible for EVT using a first-line combined technique (contact aspiration and stent retriever) or contact aspiration only will be randomised (1:1) to receive BGC balloon inflation or no inflation during EVT. OUTCOMES: The primary outcome is the proportion of patients achieving near-complete/complete vessel recanalisation (eTICI 2c-3) at the end of the EVT procedure. Secondary outcomes include the functional outcome (modified Rankin Scale at 90 days), new or distal vascular territory clot embolisation rate, near-complete/complete recanalisation after the first pass, symptomatic intracranial haemorrhage, procedure-related complications and death at 90 days. DISCUSSION: This is the first RCT to investigate the effect of proximal blood flow arrest during EVT using a BGC on the procedural and clinical outcomes of patients with AIS due to large vessel occlusion.

Incidence and predictors of poor functional outcome despite complete recanalisation following endovascular thrombectomy for acute ischaemic stroke.

BACKGROUND: Numerous ischaemic stroke patients experience poor functional outcome despite successful recanalisation following endovascular thrombectomy (EVT). We aimed to identify the incidence and predictors of futile complete recanalisation (FCR) in a national stroke registry. METHODS: Patients who achieved complete recanalisation (mTICI 3) following EVT, between October 2015 and March 2020, were included from a United Kingdom national stroke registry. Modified Rankin Scale of 4-6 at discharge was defined as a 'poor/futile outcome'. Backward stepwise multivariable logistic regression analysis was performed with FCR as the dependent variable, incorporating all baseline characteristics, procedural time metrics and post-procedural events. RESULTS: We included 2132 of 4383 patients (48.8%) with complete recanalisation post-EVT, of which 948 patients (44.4%) developed FCR. Following multivariable regression analysis adjusted for potential confounders, patients with FCR were associated with multiple baseline patient, imaging and procedural factors: age (p=0.0001), admission NIHSS scores (p=0.0001), pre-stroke disability (p=0.007), onset-to-puncture (p=0.0001) and procedural times (p=0.0001), presence of diabetes (p=0.005), and use of general anaesthesia (p=0.0001). Although not predictive of outcome, post-procedural events including development of any intracranial haemorrhage (ICH) (p=0.0001), symptomatic ICH (sICH) (p=0.0001) and early neurological deterioration (END) (p=0.007) were associated with FCR. CONCLUSION: Nearly half of patients in this national registry experienced FCR following EVT. Significant predictors of FCR included increasing age, admission NIHSS scores, pre-stroke disability, onset-to-puncture and procedural times, presence of diabetes, atrial fibrillation, and use of general anaesthesia. Post procedural development of any ICH, sICH, and END were associated with FCR.

Whole-body MRI for cancer surveillance in ataxia-telangiectasia: A qualitative study of the perspectives of people affected by A-T and their families.

BACKGROUND/OBJECTIVES: Ataxia-telangiectasia (A-T) is a complex inherited disease associated with an increased risk of malignancy. Surveillance guidelines have demonstrated significant health benefits in other cancer predisposition syndromes. However, evidence-based guidelines for cancer screening are not currently used in the United Kingdom for people affected by A-T. This study aims to understand how people with A-T and their parents feel about cancer surveillance using whole-body magnetic resonance imaging (MRI) to inform the future development of cancer surveillance guidelines. DESIGN/METHODS: We conducted semistructured interviews with people affected by A-T. Data were analysed inductively using thematic analysis. RESULTS: Nine parents of children with A-T and four adults with A-T were interviewed. Five main themes emerged from the data, including (1) cancer screening was considered invaluable with the perceived value of early detection highlighted; (2) the cancer fear can increase anxiety; (3) the perceived limitations around current practice, with the responsibility for monitoring falling too strongly on parents and patients; (4) the need for effective preparation for cancer screening, including clear communication and (5) the challenges associated with MRI screening, where specific recommendations were made for improving the child's experience. CONCLUSION: This study suggests that stakeholders are positive about the perceived advantages of a cancer screening programme. Ongoing support and preparation techniques should be adopted to maximise adherence and minimise adverse psychosocial outcomes. PATIENT OR PUBLIC CONTRIBUTION: People with A-T and parents of people with A-T were actively involved in this study by giving their consent to be interviewed. An independent parent representative contributed to the study, supporting the research team in interpreting and commenting on the appropriateness of the language used in this report.

Association between time to treatment and clinical outcomes in endovascular thrombectomy beyond 6 hours without advanced imaging selection.

BACKGROUND: The effectiveness and safety of endovascular thrombectomy (EVT) in the late window (6-24 hours) for acute ischemic stroke (AIS) patients selected without advanced imaging is undetermined. We aimed to assess clinical outcomes and the relationship with time-to-EVT treatment beyond 6 hours of stroke onset without advanced neuroimaging. METHODS: Patients who underwent EVT selected with non-contrast CT/CT angiography (without CT perfusion or MR imaging), between October 2015 and March 2020, were included from a national stroke registry. Functional and safety outcomes were assessed in both early (<6 hours) and late windows with time analyzed as a continuous variable. RESULTS: Among 3278 patients, 2610 (79.6%) and 668 (20.4%) patients were included in the early and late windows, respectively. In the late window, for every hour delay, there was no significant association with shift towards poorer functional outcome (modified Rankin Scale (mRS)) at discharge (adjusted common OR 0.98, 95% CI 0.94 to 1.01, p=0.27) or change in predicted functional independence (mRS ≤2) (24.5% to 23.3% from 6 to 24 hours; aOR 0.99, 95% CI0.94 to 1.04, p=0.85). In contrast, predicted functional independence was time sensitive in the early window: 5.2% reduction per-hour delay (49.4% to 23.5% from 1 to 6 hours, p=0.0001). There were similar rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 4.6%, p=0.54) and in-hospital mortality (12.9% vs 14.6%, p=0.33) in the early and late windows, respectively, without a significant association with time. CONCLUSION: In this real-world study, there was minimal change in functional disability, sICH and in-hospital mortality within and across the late window. While confirmatory randomized trials are needed, these findings suggest that EVT remains feasible and safe when performed in AIS patients selected without advanced neuroimaging between 6-24 hours from stroke onset.

Endovascular thrombectomy beyond 24 hours from ischemic stroke onset: a propensity score matched cohort study.

BACKGROUND: The safety and functional outcome of endovascular thrombectomy (EVT) in the very late (VL; >24 hours) time window from ischemic stroke onset remains undetermined. METHODS: Using data from a national stroke registry, we used propensity score matched (PSM) individual level data of patients who underwent EVT, selected with CT perfusion or non-contrast CT/CT angiography, between October 2015 and March 2020. Functional and safety outcomes were assessed in both late (6-24 hours) and VL time windows. Subgroup analysis was performed of imaging selection modality in the VL time window. RESULTS: We included 1150 patients (late window: 1046 (208 after PSM); VL window: 104 (104 after PSM)). Compared with EVT treatment initiation between 6 and 24 hours, patients treated in the VL window had similar modified Rankin Scale (mRS) scores at discharge (ordinal shift; common OR=1.08, 95% CI 0.69 to 1.47, p=0.70). No significant differences in achieving good functional outcome (mRS ≤2 at discharge; 28.8% (VL) vs 29.3% (late), OR=0.97, 95% CI 0.58 to 1.64, p=0.93), successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b-3) (p=0.77), or safety outcomes of symptomatic intracranial hemorrhage (p=0.43) and inhospital mortality (p=0.23) were demonstrated. In the VL window, there was no significant difference in functional outcome among patients selected with perfusion versus those selected without perfusion imaging (common OR=1.38, 95% CI 0.81 to 1.76, p=0.18). CONCLUSION: In this real world study, EVT beyond 24 hours from stroke onset or last known well appeared to be feasible, with comparable safety and functional outcomes to EVT initiation between 6 and 24 hours. Randomized trials assessing the efficacy of EVT in the VL window are warranted, but may only be feasible with a large international collaborative approach.

Association between anesthesia modality and clinical outcomes following endovascular stroke treatment in the extended time window.

BACKGROUND: There is a paucity of data on anesthesia-related outcomes for endovascular treatment (EVT) in the extended window (>6 hours from ischemic stroke onset). We compared functional and safety outcomes between local anesthesia (LA) without sedation, conscious sedation (CS) and general anesthesia (GA). METHODS: Patients who underwent EVT in the early (<6 hours) and extended time windows using LA, CS, or GA between October 2015 and March 2020 were included from a UK national stroke registry. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, pre-stroke disability, EVT technique, center, procedural time and IV thrombolysis. RESULTS: A total of 4337 patients were included, 3193 in the early window (1135 LA, 446 CS, 1612 GA) and 1144 in the extended window (357 LA, 134 CS, 653 GA). Compared with GA, patients treated under LA alone had increased odds of an improved modified Rankin Scale (mRS) score at discharge (early: adjusted common (ac) OR=1.50, 95% CI 1.29 to 1.74, p=0.001; extended: acOR=1.29, 95% CI 1.01 to 1.66, p=0.043). Similar mRS scores at discharge were found in the LA and CS cohorts in the early and extended windows (p=0.21). Compared with CS, use of GA was associated with a worse mRS score at discharge in the early window (acOR=0.73, 95% CI 0.45 to 0.96, p=0.017) but not in the extended window (p=0.55). There were no significant differences in the rates of symptomatic intracranial hemorrhage or in-hospital mortality across the anesthesia modalities in the extended window. CONCLUSION: LA without sedation during EVT was associated with improved functional outcomes compared with GA, but not CS, within and beyond 6 hours from stroke onset. Prospective studies assessing anesthesia-related outcomes in the extended time window are warranted.

Semantic Segmentation of Spontaneous Intracerebral Hemorrhage, Intraventricular Hemorrhage, and Associated Edema on CT Images Using Deep Learning.

This study evaluated deep learning algorithms for semantic segmentation and quantification of intracerebral hemorrhage (ICH), perihematomal edema (PHE), and intraventricular hemorrhage (IVH) on noncontrast CT scans of patients with spontaneous ICH. Models were assessed on 1732 annotated baseline noncontrast CT scans obtained from the Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (ie, TICH-2) international multicenter trial (ISRCTN93732214), and different loss functions using a three-dimensional no-new-U-Net (nnU-Net) were examined to address class imbalance (30% of participants with IVH in dataset). On the test cohort (n = 174, 10% of dataset), the top-performing models achieved median Dice similarity coefficients of 0.92 (IQR, 0.89-0.94), 0.66 (0.58-0.71), and 1.00 (0.87-1.00), respectively, for ICH, PHE, and IVH segmentation. U-Net-based networks showed comparable, satisfactory performances on ICH and PHE segmentations (P > .05), but all nnU-Net variants achieved higher accuracy than the Brain Lesion Analysis and Segmentation Tool for CT (BLAST-CT) and DeepLabv3+ for all labels (P < .05). The Focal model showed improved performance in IVH segmentation compared with the Tversky, two-dimensional nnU-Net, U-Net, BLAST-CT, and DeepLabv3+ models (P < .05). Focal achieved concordance values of 0.98, 0.88, and 0.99 for ICH, PHE, and ICH volumes, respectively. The mean volumetric differences between the ground truth and prediction were 0.32 mL (95% CI: -8.35, 9.00), 1.14 mL (-9.53, 11.8), and 0.06 mL (-1.71, 1.84), respectively. In conclusion, U-Net-based networks provide accurate segmentation on CT images of spontaneous ICH, and Focal loss can address class imbalance. International Clinical Trials Registry Platform (ICTRP) no. ISRCTN93732214 Supplemental material is available for this article. © RSNA, 2022 Keywords: Head/Neck, Brain/Brain Stem, Hemorrhage, Segmentation, Quantification, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms.

Cerebral Amyloid Angiopathy and the Risk of Hematoma Expansion.

OBJECTIVE: We assessed whether hematoma expansion (HE) and favorable outcome differ according to type of intracerebral hemorrhage (ICH). METHODS: Among participants with ICH enrolled in the TICH-2 (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) trial, we assessed baseline scans for hematoma location and presence of cerebral amyloid angiopathy (CAA) using computed tomography (CT, simplified Edinburgh criteria) and magnetic resonance imaging (MRI; Boston criteria) and categorized ICH as lobar CAA, lobar non-CAA, and nonlobar. The main outcomes were HE and favorable functional outcome. We constructed multivariate regression models and assessed treatment effects using interaction terms. RESULTS: A total of 2,298 out of 2,325 participants were included with available CT (98.8%; median age = 71 years, interquartile range = 60-80 years; 1,014 female). Additional MRI was available in 219 patients (9.5%). Overall, 1,637 participants (71.2%) had nonlobar ICH; the remaining 661 participants (28.8%) had lobar ICH, of whom 202 patients had lobar CAA-ICH (8.8%, 173 participants according to Edinburgh and 29 participants according to Boston criteria) and 459 did not (lobar non-CAA, 20.0%). For HE, we found a significant interaction of lobar CAA ICH with time from onset to randomization (increasing risk with time, pinteraction  < 0.001) and baseline ICH volume (constant risk regardless of volume, pinteraction  < 0.001) but no association between type of ICH and risk of HE or favorable outcome. Tranexamic acid significantly reduced the risk of HE (adjusted odds ratio = 0.7, 95% confidence interval = 0.6-1.0, p = 0.020) without statistically significant interaction with type of ICH (pinteraction  = 0.058). Tranexamic acid was not associated with favorable outcome. INTERPRETATION: Risk of HE in patients with lobar CAA-ICH was not independently increased but seems to have different dynamics compared to other types of ICH. The time window for treatment of CAA-ICH to prevent HE may be longer. ANN NEUROL 2022;92:921-930.

Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland.

Neonatal stroke is a devastating condition that causes brain injury in babies and often leads to lifelong neurological impairment. Recent prospective population studies of neonatal stroke are lacking. Neonatal strokes are different from those in older children and adults. A better understanding of its aetiology, current management, and outcomes could reduce the burden of this rare condition. The study aims to explore the incidence and 2 year outcomes of neonatal stroke across an entire population in the UK and Republic of Ireland. This is an active national surveillance study using a purpose-built integrated case notification-data collection online platform. Over a 13 month period, with a potential 6 month extension, clinicians will notify neonatal stroke cases presenting in the first 90 days of life electronically via the online platform monthly. Clinicians will complete a primary questionnaire via the platform detailing clinical information, including neuroimaging, for analysis and classification. An outcome questionnaire will be sent at 2 years of age via the platform. Appropriate ethics and regulatory approvals have been received. The neonatal stroke study represents the first multinational population surveillance study delivered via a purpose-built integrated case notification-data collection online platform and data safe haven, overcoming the challenges of setting up the study.

Perfusion Imaging for Endovascular Thrombectomy in Acute Ischemic Stroke Is Associated With Improved Functional Outcomes in the Early and Late Time Windows.

BACKGROUND: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice. METHODS: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (<6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2). RESULTS: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; P=0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P=0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage (P=0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P=0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; P=0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; P=0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; P=0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; P=0.047). CONCLUSIONS: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.