ImportanceDual antiplatelet therapy (DAPT) appears to be an effective treatment option for minor (nondisabling) acute ischemic stroke. This conclusion is based on trials that include both transient ischemic attack (TIA) and minor stroke; however, these 2 conditions may differ.ObjectiveTo compare DAPT regimens specifically for minor stroke.Data SourcesPubMed was searched for randomized clinical trials published up to November 4, 2023. Search terms strategy included TIA, transient ischemic attack, minor stroke, or moderate stroke, with the filter randomized controlled trial. Unpublished data on minor stroke were sourced from authors and/or institutions.Study SelectionTrials testing DAPT within the first 24 hours of a minor stroke (defined as a National Institutes of Health Stroke Scale score ≤5) were included by consensus. Of 1508 studies screened, 6 (0.3%) initially met inclusion criteria and were reviewed.Data Extraction and SynthesisThe study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by multiple observers. Bayesian fixed-effect network meta-analysis was conducted. Secondary analysis performed for high-risk TIA alone.Main Outcomes and MeasuresTreatments were ranked using a probability measure called surface under the cumulative rank curve (SUCRA). The primary outcome was subsequent ischemic stroke at 90 days. Secondary outcomes included major hemorrhage, mortality, and hemorrhagic stroke. The number needed to treat (NNT) and number needed to harm (NNH) were obtained.ResultsFive trials were included that described 28 148 patients, of whom 22 203 (78.9%) had a minor stroke. Of these, 13 995 (63.0%) were in DAPT groups and 8208 (37.0%) in aspirin (acetylsalicylic acid) groups. Aspirin and ticagrelor had a 94% probability of being the superior treatment for minor stroke (SUCRA, 0.94) for the primary outcome. Both aspirin and ticagrelor (NNT, 40; 95% CI, 31-64) and aspirin and clopidogrel (NNT, 58; 95% CI, 39-136) were superior to aspirin alone in the prevention of recurrent ischemic stroke at 90 days. Both treatments had higher rates of major hemorrhage than aspirin alone (NNH for aspirin and ticagrelor, 284; 95% CI, 108-1715 vs NNH for aspirin and clopidogrel, 330; 95% CI, 118-3430), but neither had increased risk of hemorrhagic stroke or death. For high-risk TIA, ticagrelor and aspirin had a 60% probability (SUCRA, 0.60) and clopidogrel and aspirin had a 40% probability (SUCRA 0.40) of being a superior treatment; neither was optimum, but both were superior to aspirin alone for the primary outcome.Conclusions and RelevanceThese findings suggest that DAPT with aspirin and ticagrelor has higher probability of being the superior treatment among patients with minor stroke when presence of CYP2C19 loss-of-function alleles has not been excluded. For patients with TIA, the superiority of aspirin and ticagrelor vs aspirin and clopidogrel was not demonstrated.

Introduction: The head impulse test (HIT) and HIT combined with direction-changing Nystagmus-Test of Skew deviation (HINTS) have been proposed as bedside tests to differentiate between peripheral and central causes of vertigo in the emergency department (ED). We conducted a meta-analysis of the HIT and HINTS tests to diagnose peripheral vertigo (PV) and central vertigo. Methods: Pubmed, Google Scholar, EmBase, and articles references published in English up to July 2021 were searched for keywords "vertigo " or "acute vestibular syndrome " or "dizziness " and "head impulse " and "stroke. " The bivariate method for meta-analysis was used to calculate positive (PLR) and negative likelihood ratios (NLR) and summary receiver operating characteristics area under the curve (AUC). Results: A total of 11 studies were included analysing both HIT (8 studies, N = 417) and HINTS (6 studies, N = 405). HIT and HINTS were performed within 24 h in 4 of 11 studies. PLR and NLR for HIT in PV was 4.85 (95% CI: 2.83-8.08) and 0.19 (95% CI: 0.12-0.29, I-2 63.25%), respectively. The AUC for HIT the diagnosis of PV and stroke was 0.90 and 0.92, respectively. PLR and NLR for a negative HIT in stroke was 5.85 (95% CI: 3.07-10.6) and 0.17 (95% CI: 0.08-0.30), respectively. PLR and NLR for peripheral HINTS pattern for PV was 17.3 (95% CI: 8.38-32.1) and 0.15 (95% CI: 0.07-0.26), respectively. PLR and NLR for central HINTS pattern for stroke: 5.61 (95% CI: 4.19-7.7) and 0.06 (95% CI: 0.03-0.12). In all included studies, HIT and HINTS exams were administered by neurology residents or neurology specialists with additional neuro-otology or neuro-ophthalmology subspeciality experience, and two studies included ED physicians. Raters reported high degree of bias and high concern regarding applicability in most domains of the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Meta-regression did not demonstrate a statistically significant effect of publication year, time to test, and type of assessor on sensitivity or false positive rate. Conclusion: The HIT and HINTS exams appear to be moderately good discriminators of central and PV. However, in most papers, the tests were administered by neurologists and were evaluated beyond 24 h, which may limit utility in the ED setting.

Background Post-stroke pneumonia is a frequent complication of stroke and is associated with high mortality. Investigators have described its associations with beta-blocker. However, there has been no evaluation of the role of recombinant tissue plasminogen activator (RTPA). We postulate that RTPA may modify the effect of stroke on pneumonia by reducing stroke disability. We explore this using data from neuroprotection trials in Virtual International Stroke Trials Archive (VISTA)-Acute. Method We evaluated the impact of RTPA and other medications in random forest model. Random forest is a type of supervised ensemble tree-based machine learning method. We used the standard approach for performing random forest and partitioned the data into training (70%) and validation (30%) sets. This action enabled to the model developed on training data to be evaluated in the validation data. We borrowed idea from Coalition Game Theory on fair distribution of marginal profit (Shapley value) to determine proportional contribution of a covariate to the model. Consistent with other analysis using the VISTA-Acute data, the diagnosis of post-stroke pneumonia was based on reports of serious adverse events. Results The overall frequency of pneumonia was 10.9% (614/5652). It was present in 11.5% of the RTPA (270/2358) and 10.4% (344/3295) of the no RTPA groups. There was significant (p<0.05) imbalance in covariates (age, baseline National Institutes of Health Stroke Scale (NIHSS), diabetes, and sex). The AUC for training data was 0.70 (95% CI 0.65–0.76), validation data was 0.67 (95% CI 0.62–0.73). The Shapley value shows that baseline NIHSS (≥10) and age (≥80) made the largest contribution to the model of pneumonia while absence of benzodiazepine may protect against pneumonia. RTPA and beta-blocker had very low effect on frequency of pneumonia. Conclusion In this cohort pneumonia was strongly associated with stroke severity and age whereas RTPA had a much lower effect. An intriguing finding is a possible association between benzodiazepine and pneumonia but this requires further evaluation.

BackgroundWe proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.MethodsThe design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke.ResultsEight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload.ConclusionOur Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.Clinical trial registrationClinicalTrials.gov, identifier ACTRN12618000076279P.

Objectives We conducted a meta-analysis of the HIT and HINT tests to diagnose peripheral vertigo (PV) and central vertigo in the emergency department (ED). Methods Pubmed, Google Scholar, EmBase and articles references published in English up to July 2021 were searched for keywords 'vertigo' or 'acute vestibular syndrome' or 'dizziness' and 'head impulse' and 'stroke'. Bivariate method for meta-analysis was used. Results 11 studies HIT (8 studies, N = 417) and HINT (6 studies, N = 405). HIT and HINT were performed within 24 hours in 4 of 11 studies. Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) for HIT in PV was 4.85 (95% CI 2.83 – 8.08) and 0.19 (95% CI 0.12 – 0.29, I263.25%) respectively. The (area under the curve) AUC for HIT the diagnosis of PV and stroke was 0.90 and 0.92 respectively. PLR and NLR for a negative HIT in stroke was 5.85 (95% CI 3.07 – 10.6) and 0.17 (95% CI 0.08 – 0.30) respectively. PLR and NLR for peripheral HINT pattern for PV was 17.3 (95% CI 8.38 – 32.1) and 0.15 (95% CI 0.07 – 0.26) respectively. PLR and NLR for central HINT pattern for stroke was 5.61 (95% CI 4.19 – 7.7) and 0.06 (95% CI 0.03 – 0.12) respectively. Conclusion The HIT and HINT exams appear moderately good discriminators of central and peripheral vertigo. However, these results may not apply in the ED setting as most papers evaluated these tests beyond 24 hours.

BACKGROUND:The natural history of patients with stroke and cancer remains poorly understood in the modern era of hyperacute stroke therapies (recombinant tissue plasminogen activator and endovascular clot retrieval (ECR)). Prior to these advances in stroke treatment, a highly cited study reported median overall survival (mOS) 4.5 months after stroke in a cohort of patients with cancer (2004, n = 96).AIMS:Our hypothesis is that patients with stroke and cancer have better outcome than in earlier studies.METHODS:Retrospective analysis of admission to a tertiary Stroke Unit between January 2015 and September 2017 (n = 1910), evaluation of hospital records and cancer treatment records. Cancer was categorised as early stage (Stages I and II) and advanced stage (Stage III or IV) using the RD-Staging system. Survival analysis was performed in R.RESULTS:There were 143 stroke patients with cancer (62% male) with mean age 73.2 ± 12.5 years. Ischaemic stroke occurred in 74.1% and 45 of 106 (42.5%) patients received intravenous thrombolysis (34/45) and/or ECR (11/45). One patient who received ECR died within 30 days of stroke. Those with early stage disease had mOS of 19.6 months (interquartile range (IQR) 3.1-31.5 months) and in advanced stage cancer mOS was 2.5 months (IQR 0.4-6.3 months; P < 0.01).CONCLUSION:In the modern era of stroke therapy, our cohort of patients with advanced cancer has lower survival post-stroke compared to those with early stage cancer.

Background: There is emphasis on timely administration of thrombolysis and clot retrieval but not antithrombotic therapy within 48 h for ischemic stroke (frequency of 64% in Australia and 97% in North America). We planned to assess the time metrics and variables associated with delaying antithrombotics (antiplatelet and anticoagulant therapy) administration.Methods: This was a retrospective study at Monash Health over 12 months in 2015. We plotted the cumulative event and mapped the key drivers (dimensionless variable Shapley value/SV) of antithrombotics.Results: There were 42 patients with transient ischemic attack/TIA and 483 with ischemic stroke [mean age was 71.8 ± 15.4; 56.0% male; nil by mouth (NBM) 74.5 and 49.3% of patients received “stat” (immediate and one off) dose antithrombotics]. The median time to imaging for the patients who did not have stroke code activated was 2.3 h (IQR 1.4–3.7), from imaging to dysphagia screen was 14.6 h (IQR 6.2–20.3), and from stopping NBM to antithrombotics was 1.7 h (IQR 0–16.5). TIA patients received antithrombotics earlier than those with ischemic stroke (90.5 vs. 86.5%, p = 0.01). Significant variables in regression analysis for time to antithrombotics were time to dysphagia screen (β 0.20 ± 0.03, SV = 3.2), nasogastric tube (β 19.8 ± 5.9, SV = −0.20), Alteplase (β 8.6 ± 3.6, SV = −1.9), stat dose antithrombotic (β −18.9 ± 2.9, SV = −10.8) and stroke code (β −5.9 ± 2.5, SV = 2.8). The partial correlation network showed that the time to antithrombotics increased with delay in dysphagia screen (coefficient = 0.33) and decreased if “stat” dose of antithrombotics was given (coefficient = −0.32).Conclusion: The proportion of patients receiving antithrombotics within 48 h was higher than previously reported in Australia but remained lower than the standard achieved in North American hospitals. Our process map and network analysis show avenues to shorten the time to antithrombotic.

Transient Ischaemic Attack (TIA) if untreated carries a high risk of early stroke and is associated with poorer long-term survival [1]. There is emerging evidence of a reduction in stroke risk following TIA. Time critical investigations and management, as well as service organisation remain key to achieving good outcomes. Patients are diagnosed with TIA if they have transient, sudden-onset focal neurological symptoms which usually completely and rapidly resolve by presentation. The tissue based definition of TIA guides the fact that patients with residual symptoms should be considered as potentially having a stroke, with urgent evaluation regarding eligibility for thrombolysis and/or endovascular clot retrieval (ECR). Essential investigations for all patients with TIA should include early brain imaging, ECG, and carotid imaging in patients with anterior circulation symptoms. After brain imaging, exclusion of high risk indicators and immediate administration of an antiplatelet agent, subsequent attention to other mechanistic factors can be managed safely as part of a structured clinical pathway supervised by stroke specialists. This is in line with the recently revised Stroke Foundation Clinical Guidelines for Stroke Management (2017). (C) 2019 Elsevier Ltd. All rights reserved.

The Deauville score (DS) is a clinical tool, based on the comparison between lesion and reference organ uptake of 18F-fluorodeoxyglucose (FDG), used to stratify patients with lymphoma into categories reflecting their disease status. With a plethora of positron emission tomography with computed tomography (PET-CT) hard- and software algorithms, standard uptake value (SUV) in lesions and reference organs may differ which affects DS classification and therefore medical treatment. The EANM Research Ltd. (EARL) harmonization program from the European Association of Nuclear Medicine (EANM) partly mitigates this issue, but local preferences are common in clinical practice. We have investigated the discordance in DS calculated from patients with lymphoma referred for 18F-FDG PET-CT reconstructed with three different algorithms: the newly introduced block-sequential regularization expectation-maximization algorithm commercially sold as Q. Clear (QC, GE Healthcare, Milwaukee, WI, USA), compliant with the newly proposed updated EARL recommendations, and two settings compliant with the current EARL recommendations (EARLlower and EARLupper, representing the lower and upper limit of the EARL recommendations). Fifty-two patients with non-Hodgkin and Hodgkin lymphoma were included (18 females and 34 males). Segmentation of mediastinal blood pool and liver were semi-automatically performed, whereas segmentation of lesions was done manually. From these segmentations, SUVmax and SUVpeak were obtained and DS calculated. There was a significant difference in DS between the QC algorithm and EARLlower/EARLupper (p < 0.0001 for both) but not between EARLlower and EARLupper (p = 0.102) when SUVmax was used. For SUVpeak, there was a significant difference between QC and EARLlower (p = 0.001), but not for QC vs EARLupper (p = 0.071) or EARLlower vs EARLupper (p = 0.102). Five non-responders (DS 4–5) for QC were classified as responders (DS 1–3) when EARLlower/EARLupper was used, both when SUVmax and SUVpeak were investigated. Using the proposed updated EARL recommendations compared with the current recommendations will significantly change DS classification. In select cases, the discordance would affect the choice of medical treatment. Specifically, the current EARL recommendations were more often prone to classify patients as responders.

Background and Purpose: Post-stroke pneumonia is a feared complication of stroke as it is associated with greater mortality and disability than in those without pneumonia. Patients are often kept "Nil By Mouth" (NBM) after stroke until after receiving a screen for dysphagia and declared safe to resume oral intake. We aimed to assess the proportional contribution of stroke severity and dysphagia screen to pneumonia by borrowing idea from coalition game theory on fair distribution of marginal profit (Shapley value). Method: Retrospective study of admissions to the stroke unit at Monash Medical Center in 2015. Seventy-five percent of data were partitioned into training set and the remainder (25%) into validation set. Variables associated with pneumonia (p < 0.1) were entered into Shapley value regression and conditional decision tree analysis. Results: In 2015, there were 797 admissions and 617 patients with ischemic and hemorrhagic stroke (age 69.9 ± 16.2, male = 55.0%, National Institute of Health Stroke Scale/NIHSS 8.1 ± 7.9). The frequency of pneumonia was 6.6% (41/617). In univariable analyses NIHSS, time to dysphagia screen, Charlson comorbidity index (CCI), and age were significantly associated with pneumonia but not weekend admission. Shapley value regression showed that the largest contributor to the model was stroke severity (72.8%) followed by CCI (16.2%), dysphagia screen (3.8%), and age (7.2%). Decision tree analysis yielded an NIHSS threshold of 14 for classifying people with (27% of 75 patients) and without pneumonia (2.5% of 308 patients). The area under the ROC curve for training data was 0.83 (95% CI 0.75-0.91) with no detectable difference between the training and test data (p = 0.4). Results were similar when dysphagia was exchanged for the variable dysphagia screen. Conclusion: Stroke severity status, and not dysphagia or dysphagia screening contributed to the decision tree model of post stroke pneumonia. We cannot exclude the chance that using dysphagia screen in this cohort had minimized the impact of dysphagia on development of pneumonia.

Background: Prognostication following hypoxic ischemic encephalopathy (brain injury) is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data. Method: The inclusion criteria were as follows: age >= 17 years, cardio-respiratory arrest, and coma on admission (2003-2011). Decision tree analysis was used to find clinical [ Glasgow Coma Score (GCS), features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume) associates of severe disability and death. We used the area under the ROC (auROC) to determine accuracy of model. There were 41 (63.7% males) patients having MRI imaging with the average age 51.5 +/- 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82-1.00). At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86-1.00). Conclusion: Our findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

Background and Purpose— There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub. Methods— Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval–capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs. Results— In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km 2 and MMC 1164 km 2 ) or with AUS (model 1c, RMH 1244 km 2 and AUS 1685 km 2 ), with no statistical difference between models ( P =0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km 2 and ALF 676 km 2 ), significantly different from both models 1a and 1c (both P <0.05). Model 1a had the greatest proportion of patients arriving within ideal time of 30 minutes followed by model 1c ( P <0.001). In a 3-hub model, the combination of RMH, MMC, and AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability. Conclusions— We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs.

Background and purpose: Cerebral microbleeds (CMBs), cortical superficial siderosis, white matter lesions (WML), and cerebral atrophy may signify greater bleeding risk particularly in patients in whom anticoagulation is to be considered. We investigated their prevalence and associations with stroke type in patients with stroke and atrial fibrillation (AF).Materials and Methods: Cross-sectional sample, Monash Medical Centre (Melbourne, Australia) between 2010 and 2013, with brain MRI. MRI abnormalities were rated using standardized methods. Logistic regression was used to study associations adjusting for age and sex.Results: There were 170 patients, mean age 78 years (SD 9.8), 154 (90.6%) with ischemic stroke. Prevalence of MRI markers were any microbleed 49%, multiple (>= 2) microbleeds 30%, confluent WMLs 18.8%, siderosis 8.9%, severe cerebral atrophy 37.7%. Combinations of the severe manifestations of these markers were much less prevalent (2.9-12.4%). Compared with ischemic stroke, those with hemorrhagic stroke were more likely to have >= 10 microbleeds (OR 5.50 95% CI 1.46-20.77, p = 0.012) and siderosis (OR 6.24, 95% CI 1.74-22.40, p = 0.005). Siderosis was associated with multiple microbleeds (OR 8.14, 95% CI 2.38-27.86, p = 0.001). Patients admitted with hemorrhagic stroke and multiple microbleeds were more frequently anticoagulated prior to stroke (6/7, 85.7%) than in those with single (1/2, 50%) or no microbleeds (4/7, 57%).Conclusion: Multiple CMBs, severe WML, and severe cerebral atrophy were common individually in hospitalized patients with stroke and AF, but less so in combination. A higher burden of CMBs may be associated with intracerebral hemorrhage in stroke patients with AF.

Background and Purpose— Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction–driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time. Methods— Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ≤18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. Results— Forty-seven patients were imaged with 11 C-PiB positron emission tomography. There was an increase in 11 C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, −0.06 to 0.123]; P =0.452). There was no significant increase in the accumulation of 11 C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, −0.02 to 0.10]; P =0.095). We repeated 11 C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of 11 C-PiB between regions of interest (median difference in standardized uptake value ratio, −0.08 [95% confidence interval, −0.23 to −0.03]; P =0.04). Conclusions— There was no significant increase in 11 C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric 11 C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased β-amyloid deposition ≤18 months after stroke.

Background: Lacunar infarcts have been characterized as small subcortical infarcts, resulting from in situ microatheroma or lipohyalinosis in small vessels. Based on this hypothesis, such infarcts should not be associated with large areas of perfusion deficits extending beyond subcortical regions to involve cortical regions. By contrast, selected small subcortical infarcts, as defined by MR imaging in the subacute or chronic stage, may initially have large perfusion deficits or related large vessel occlusions. These infarcts with ‘lacunar’ phenotype may also be caused by disease in the parent vessel and may have very different stroke mechanisms from small vessel disease. Our aim was to describe differences in imaging characteristics between patients with small subcortical infarction with ‘lacunar phenotype’ from those with lacunar mechanism. Methods: Patients undergoing acute CT Perfusion/angiography (CTP/CTA) within 6 hours of symptom onset and follow-up magnetic resonance imaging (MRI) for ischaemic stroke were included (2009-2013). A lacunar infarct was defined as a single subcortical infarct (SSI) ≤20 mm on follow-up MRI. Presence of perfusion deficits, vessel occlusion and infarct dimensions were compared between lacunar infarcts and other topographical infarct types. Results: Overall, 182 patients (mean age 66.4±15.3 years, 66% male) were included. SSI occurred in 31 (17%) patients. Of these, 12 (39%) patients had a perfusion deficit compared with those with any cortical infarction (120/142, 67%), and the smallest SSI with a perfusion deficit had a diameter of <5mm. The majority of patients with SSI (8/12, 66.7%) had a relevant vessel occlusion. A quarter of SSIs had a large-artery stroke mechanism evident on acute CTP/CTA. Lacunar mechanism was present in 3/8 patients with corona radiata, 5/10 lentiform nucleus, 5/6 posterior limb of internal capsule PLIC, 3/5 thalamic infarcts and 1/2 miscellaneous locations. There was a trend toward significance with regard to finding a lacunar mechanism among patients with thalamic and PLIC versus lentiform nucleus and corona radiata infarcts (p=0.13). Conclusion: Diverse stroke mechanisms were present among subcortical infarcts in different locations. Whenever available, acute CTP/CTA should be combined with subacute imaging of subcortical infarcts to differentiate the ‘lacunar phenotype’ from subcortical infarcts with lacunar mechanism.

Background and Purpose Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of -amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger -amyloid deposition, with deposition over time.Methods Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup 18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration.Results Forty-seven patients were imaged with C-11-PiB positron emission tomography. There was an increase in C-11-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, -0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of C-11-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, -0.02 to 0.10]; P=0.095). We repeated C-11-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of C-11-PiB between regions of interest (median difference in standardized uptake value ratio, -0.08 [95% confidence interval, -0.23 to -0.03]; P=0.04).Conclusions There was no significant increase in C-11-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric C-11-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased -amyloid deposition 18 months after stroke.

Background and aim The availability and access of hospital administrative data [coding for Charlson comorbidity index (CCI)] in large data form has resulted in a surge of interest in using this information to predict mortality from stroke. The aims of this study were to determine the minimum clinical data set to be included in models for predicting disability after ischemic stroke adjusting for CCI and clinical variables and to evaluate the impact of CCI on prediction of outcome. Method We leverage anonymized clinical trial data in the Virtual International Stroke Trials Archive. This repository contains prospective data on stroke severity and outcome. The inclusion criteria were patients with available stroke severity score such as National Institutes of Health Stroke Scale (NIHSS), imaging data, and outcome disability score such as 90-day Rankin Scale. We calculate CCI based on comorbidity data in this data set. For logistic regression, we used these calibration statistics: Nagelkerke generalised R2 and Brier score; and for discrimination we used: area under the receiver operating characteristics curve (AUC) and integrated discrimination improvement (IDI). The IDI was used to evaluate improvement in disability prediction above baseline model containing age, sex, and CCI. Results The clinical data among 5,206 patients (55% males) were as follows: mean age 69 ± 13 years, CCI 4.2 ± 0.8, and median NIHSS of 12 (IQR 8, 17) on admission and 9 (IQR 5, 15) at 24 h. In Model 2, adding admission NIHSS to the baseline model improved AUC from 0.67 (95% CI 0.65–0.68) to 0.79 (95% CI 0.78–0.81). In Model 3, adding 24-h NIHSS to the baseline model resulted in substantial improvement in AUC to 0.90 (95% CI 0.89–0.91) and increased IDI by 0.23 (95% CI 0.22–0.24). Adding the variable recombinant tissue plasminogen activator did not result in a further change in AUC or IDI to this regression model. In Model 3, the variable NIHSS at 24 h explains 87.3% of the variance of Model 3, follow by age (8.5%), comorbidity (3.7%), and male sex (0.5%). Conclusion Our results suggest that prediction of disability after ischemic stroke should at least include 24-h NIHSS and age. The variable CCI is less important for prediction of disability in this data set.

ABSTRACT BACKGROUND Cerebral amyloid angiopathy (CAA) has been reported to present as convexity subarachnoid hemorrhage (cSAH). Lesser known is that cSAH can herald intracerebral hemorrhage (ICH) and ischemic lesions. We present seven new cases with 11 C‐Pittsburgh compound B (PiB) positive positron emission tomography (PET) scans including two with biopsy, review the literature and comment on clinical and radiological findings. METHODS Patients with cSAH identified on CT, underwent MR imaging and MR angiography to exclude intracranial aneurysm. Nonaneurysmal cSAH were further prospectively evaluated for amyloid angiopathy using PiB. Clinical and radiological features of cSAH, subsequent ICH and ischemic lesions were characterized. RESULTS Seven patients with nonaneurysmal cSAH fulfilled the Boston criteria for probable CAA. All had PiB PET scans consistent with CAA. Of the 4 patients who had contrast MR Imaging all had enhancement overlying the cSAH, followed by ICH in three cases. All patients presented with transient sensory symptoms. All patients had small punctate subcortical and cortical infarcts on diffusion‐weighted MR imaging. Literature review revealed subsequent ICH in approximately 11/79 patients. CONCLUSION The finding of cSAH and PiB binding in our patients suggest underlying CAA. cSAH may be associated with ischemic lesion as well as future ICH occurrence.

BACKGROUND:It has been described that lacunar infarct is characterized by its smallish size (15-20 mm) in the axial plane. However, the size of the basal ganglia artery responsible for this type of infarct is uncertain. Detection of small arterial occlusion is not possible with current angiography, hindering correlation of arterial occlusion with subcortical infarct size. Recently, investigators have published microangiographic templates of arteries supplying the basal ganglia. These templates display first-order (proximal) to third-order (distal) branching of these arteries and can help with estimating the likely site of arterial disease in subcortical infarcts. We correlated the dimensions of subcortical infarcts with the order of arterial branching described in a microangiographic template. Such data may provide further clues about the type of arteries associated with subcortical infarcts and assist in refining the concept of lacunar infarction.METHOD:Patients with subcortical infarcts on MR imaging (MRI) admitted to our institution between 2009 and 2011 were included in the study. Infarcts were manually segmented and registered to a standard brain template. These segmented infarcts were scaled and overlapped with published microangiographic templates, and used by 6 raters who independently estimated the branching order of arterial disease that might result in these infarcts. We used regression analysis to relate these ratings to infarct dimensions.RESULTS:Among 777 patients, there were 33 (58% male) patients with subcortical infarcts. The mean age was 63.1 ± 15.1 years. Infarct dimensions for the groups were as follows: group 1 (first-order branch): height 37.6 ± 7.4 mm, horizontal width 21.2 ± 11.6 mm, anterior-posterior length 36.8 ± 20.1 mm; group 2 (second-order branch): height 25.2 ± 7.9 mm, horizontal width 16.6 ± 22.8 mm, anterior-posterior length 16.1 ± 8.0 mm; group 3 (third-order branch): height 11.6 ± 5.7 mm, axial width 5.3 ± 3.1 mm, anterior-posterior length 5.5 ± 3.8 mm. Increasing vessel branching order (from large to small vessels) was linearly and negatively associated with infarct height (β = -16.7 mm per change in branching order disease, 95% CI -20.3, -13.1 mm, p < 0.01) and anterior-posterior length (β = -16.8 mm per change in branching order disease, 95% CI -23.2, -10.5 mm, p < 0.01).DISCUSSION:Based on MRI infarct dimensions and a microangiographic template, it may be possible to estimate the branching order of the artery involved in subcortical infarcts. Further, our small data set suggests that reliance on an axial dimension of 15-20 mm may not be the best approach to classifying lacunar infarct. This finding needs to be confirmed in a larger data set.