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Background Spontaneous intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with high morbidity and mortality. Branching pattern of the lenticulostriate arteries from the middle cerebral artery makes them susceptible to formation of microaneurysms, which have been implicated in hypertensive ICH. Recurrence of hematoma due to delayed development of pseudoaneurysm after initial surgical evacuation is uncommon. Case Description Our patient is a 61-year-old gentleman who underwent primary evacuation of a spontaneous right-sided ICH. The initial vascular imaging was unremarkable for any underlying vascular malformation. After initial neurologic recovery, the patient developed another rebleeding in the hematoma cavity nearly 10 days after presentation. A formal angiogram showed the presence of a pseudoaneurysm that was treated via endovascular means. Conclusions The rates of rebleeding have ranged from 10%−40% in various studies and have been directly correlated with mortality. Since follow-up with angiograms are not a usual practice in spontaneous ICH management, such as pseudoaneurysmal rebleeds could go undiagnosed. This case report reinforces the need for a thorough angiographic evaluation in the event of a deviation from expected clinical course, rebleeding not in concordance with intraoperative findings and significantly delayed hematoma recurrence.

Deep cerebral venous thrombosis (CVT) is an uncommon condition with a high morbidity and mortality. The optimal treatment approach for deep CVT remains uncertain and due to its low prevalence, randomized trials are not feasible. We showcase a straight sinus thrombosis treated with a large bore aspiration and performed a meta-analysis of the available literature to characterize and evaluate the various treatment modalities for patients with deep CVT. We conducted a systematic search in PubMed, EMBASE and Ovid Medline using appropriate keywords/MESH terms search strategy. All patients with thrombosis involving the deep venous sinuses were included if treatment records were available. Outcome measures included recanalization of the affected sinus, good functional outcome assessed by a modified Rankin scale (mRS) of 0–2 or reported independent functional outcomes, permanent neurological deficits, further hemorrhage and mortality. A total of 69 studies comprising 120 patients were included in the analysis. Anticoagulation was the most common treatment (85.8%), whilst local intrasinus thrombolysis was performed in 40.0% of the patients and mechanical endovascular modalities were employed in 20.0% of the patients. Recanalization of the occluded sinus was seen in 83.5% of the patients while 62.6% patients achieved good functional outcome. There was considerable morbidity with 60.7% having a permanent neurological deficit, 23.3% having further hemorrhage after admission and 18.6% mortality. In the cohort receiving anticoagulation, 65.3% achieved good outcome but intracranial hemorrhage at presentation was associated with poorer outcome, permanent deficits, further bleeding and mortality. Anticoagulation is an effective treatment strategy for deep CVT; however, patients with intracranial hemorrhage at presentation often have poorer outcomes and early endovascular strategies could be considered in this subgroup.

Background and Purpose: This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive baseline stroke compared with best medical treatment. Methods: This retrospective, multicenter study compares EVT and best medical treatment for computed tomography (CT)–based selection of patients with extensive baseline infarcts (Alberta Stroke Program Early CT Score ≤5) attributed to anterior circulation stroke. Patients were selected from the German Stroke Registry and 3 tertiary stroke centers. Primary functional end points were rates of good (modified Rankin Scale score of ≤3) and very poor outcome (modified Rankin Scale score of ≥5) at 90 days. Secondary safety end point was the occurrence of symptomatic intracerebral hemorrhage. Angiographic outcome was evaluated with the modified Thrombolysis in Cerebral Infarction Scale. Results: After 1:1 pair matching, a total of 248 patients were compared by treatment arm. Good functional outcome was observed in 27.4% in the EVT group, and in 25% in the best medical treatment group ( P =0.665). Advanced age (adjusted odds ratio, 1.08 [95% CI, 1.05–1.10], P P P =0.025) and symptomatic intracerebral hemorrhage (16.1% versus 5.6%, P =0.008) were significantly higher in the EVT group. The lowest rates of good functional outcome (≈15%) were observed in groups of failed and partial recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 0/1–2a), whereas patients with complete recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 3) with recanalization attempts ≤2 benefitted the most (modified Rankin Scale score of ≤3:42.3%, P =0.074) compared with best medical treatment. Conclusions: In daily clinical practice, EVT for CT–based selected patients with low Alberta Stroke Program Early CT Score anterior circulation stroke may not be beneficial and is associated with increased risk for hemorrhage and mortality, especially in the elderly. However, first- or second-pass complete recanalization seems to reveal a clinical benefit of EVT highlighting the vulnerability of the low Alberta Stroke Program Early CT Score subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03356392.

BackgroundEndovascular thrombectomy (EVT) in large vessel occlusion (LVO) in anterior circulation acute ischaemic stroke (AIS) results in good functional outcomes in only approximately 60% of the patients. Internal cerebral veins (ICVs) are easily visible, with a consistent midline location, and are linked to stroke outcomes. We hypothesize that ICV asymmetry on multiphasic CT angiogram (mCTA) can be an adjunctive predictor for poor functional outcomes.MethodsWe studied consecutive AIS patients from 2017 to 2019 with anterior circulation LVO treated with EVT regardless of intravenous thrombolysis. Asymmetrical ICV was defined as the presence of hypodensity (less opacification) on the ipsilateral occlusion side as compared with the contralateral side. The primary outcome was modified Rankin Score (mRS) score at 3 months. Secondary outcomes were good recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3), symptomatic hemorrhage, and mortality.ResultsA total of 185 patients were included with a median age of 70 years (IQR 59–77); 87 patients (47%) were female. 82 patients (44.3%) achieved good functional outcomes (mRS 0–2) at 3 months. On multivariate analysis, National Institutes of Health Stroke Scale (NIHSS) (OR 1.076, 95% CI 1.015 to 1.140; pConclusionICV asymmetry is a novel radiological sign which is independently associated with poor functional outcomes in EVT, even after correction for collateral circulation. Further studies are needed to validate this finding.

Background: The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. Objectives: We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. Methods: This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. Results: We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p =0.004, 95% CI 6.513 - -2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable ( p = 0.519, 95% CI -1.605 - 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 hours (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. Conclusions: The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

Introduction: Endovascular thrombectomy(EVT) is considered standard of care for anterior circulation acute ischemic stroke(AIS) with large vessel occlusion(LVO). Young AIS-LVO patients have distinctly different underlying stroke mechanisms and etiologies. Methods: In this multicenter cohort study conducted from August 2014 to January 2020, we investigated the safety and effectiveness of EVT in young AIS-LVO patients aged≤50 years and evaluated associations between demographics, stroke etiology, neuroimaging factors and clinical outcomes, including functional outcomes, in-hospital mortality and symptomatic intracranial haemorrhage(sICH) in univariable and multivariable regression models. Results: 275 AIS-LVO patients from 10 tertiary centers in Germany, Sweden, Singapore and Taiwan were included. The more common TOAST subtypes included cardioembolism (82/275, 29.8%) and stroke of undetermined etiology (85/275, 30.9%). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%) and had the highest rate of good functional outcomes (29/42, 69.0%). Successful reperfusion was achieved in 85.1% (234/275). Excellent and good functional outcomes were achieved in 48.0% (132/275) and 66.0% (182/275) respectively. sICH occurred in 6.5% (18/275). National Institute of Health Stroke Scale (NIHSS) at presentation was inversely related with good functional outcomes (aOR0.92, 95% CI 0.88- 0.96 per point increase, p Conclusion: While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT.

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p

BackgroundWhether to approach distal occlusions endovascularly or not in medium-sized vessels secondary to proximal large vessel occlusion stroke remains unanswered.ObjectiveTo investigates the technical feasibility and safety of thrombectomy for secondary posterior circulation distal, medium vessel occlusions (DMVO).MethodsTOPMOST (Treatment fOr Primary Medium vessel Occlusion STroke) is an international, retrospective, multicenter, observational registry of patients treated for distal cerebral artery occlusions. This study subanalysis endovascularly treated occlusions of the posterior cerebral artery in the P2 and P3 segment secondary preprocedural or periprocedural thrombus migration between January 2014 and June 2020. Technical feasibility was evaluated with the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Procedural safety was assessed by the occurrence of symptomatic intracranial hemorrhage (sICH) and intervention-related serious adverse events.ResultsAmong 71 patients with secondary posterior circulation DMVO who met the inclusion criteria, occlusions were present in 80.3% (57/71) located in the P2 segment and in 19.7% (14/71) in the P3 segment. Periprocedural migration occurred in 54.9% (39/71) and preprocedural migration in 45.1% (32/71) of cases. The first reperfusion attempt led in 38% (27/71) of all cases to mTICI 3. On multivariable logistic regression analysis, increased numbers of reperfusion attempts (adjusted odds ratio (aOR)=0.39, 95% CI 0.29 to 0.88, p=0.009) and preprocedural migration (aOR=4.70, 95% CI,1.35 to 16.35, p=0.015) were significantly associated with mTICI 3. sICH occurred in 2.8% (2/71).ConclusionThrombectomy for secondary posterior circulation DMVO seems to be safe and technically feasible. Even though thrombi that have migrated preprocedurally may be easier to retract, successful reperfusion can be achieved in the majority of patients with secondary DMVO of the P2 and P3 segment.

Background: Endovascular thrombectomy (ET) has transformed acute ischaemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD as measured by LVEF, and clinical outcomes in patients with anterior cerebral circulation LVO who undergo ET. Methods: This retrospective study examined patients from our AIS endovascular thrombectomy registry from 2013-2018. We included all consecutive patients who had anterior circulation LVO (ICA, M1, M2) who underwent ET, and had transthoracic two-dimensional echocardiography. LVSD was measured by assessment of the LVEF using Simpson’s biplane method of discs according to American Society of Echocardiography guidelines. LVSD was defined as a reduced LVEF of Results: Of 254 AIS patients with anterior circulation LVO, we included 229 patients with complete echocardiography assessment. On multivariate analyses, older age, diabetes mellitus, lower ASPECTS, unsuccessful recanalization, smaller LV outflow tract diameter and LVSD were significantly associated with poor functional outcomes (Table 1). On ordinal (shift) analyses, LVSD was associated with an unfavourable shift in the mRS outcomes (OR 3.09, 95% CI 1.68 - 5.69, p < 0.001) after adjusting for age and ischemic heart disease (Figure). Conclusion: Anterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to tailor peri-procedural management strategies.

Background: Intracranial thrombus characteristics on computed tomography angiography (CTA) in patients undergoing endovascular therapy (ET) for anterior circulation large vessel occlusion (LVO) acute ischemic stroke (AIS) has been shown to be useful in prognosticating functional outcomes. We establish if thrombus characteristics on non-contrast computed tomography (CT) scans and CTA were associated with clinical outcomes. Methods: We included 257 patients with anterior circulation LVO AIS from our Hyper-Acute Stroke Thrombolysis and Endovascular (HASTEN) registry treated at our tertiary academic institution from 2014-2018. We evaluated associations of patient’s characteristics and thrombus imaging characteristics with patients’ functional outcomes, scored with the modified Rankin Scale (MRS) at 3 months. Imaging characteristics were assessed on CT and CTA. Patient characteristics included age, presence of co-morbidities, initial NIHSS and ASPECTS. Thrombus characteristics included presence of hyperdense middle cerebral artery (MCA) sign, CT dense MCA length, CTA location and length of thrombus, CTA clot burden score (CBS) and recanalization status (mTICI). A good functional outcome was defined as patients who achieved an MRS of 0-2 at 3 months. Results: Patient characteristics associated with good functional outcomes were younger age, absence of diabetes mellitus, lower NIHSS, higher ASPECTS and successful recanalization measured by a mTICI 2b/3 (Table 1). Thrombus characteristics associated with good functional outcomes were a shorter CT dense MCA length and a higher CTA CBS (Table 1). Of note, presence of a hyperdense MCA sign on CT and CTA thrombus length were not significantly associated with good functional outcomes. Conclusions: In patients with anterior circulation LVO AIS, a shorter CT dense MCA length and a higher CTA CBS were associated with good functional outcomes, and may aid in improving patient selection.

Studies have shown that the modified thrombolysis in cerebral ischemia (mTICI) 2B score is associated with better functional outcome; however, 50–99% reperfusion is a large range and there may be factors which can differentiate this further. The effects of very late leptomeningeal collaterals (VLLC) on mTICI-2B patients were studied. A prospectively collected registry of anterior circulation AIS patients treated with the EmboTrap revascularization device from 2013 to 2016 was evaluated. Imaging parameters and timings, including the mTICI score were verified by an external core laboratory blinded to the clinical data. The final angiogram was examined for the appearance of VLLC in predicting 3‑month outcomes including excellent functional outcomes, defined as modified Rankin scale (mRS) 0–1, bleeding risk and mortality. A total of 177 consecutive anterior circulation stroke patients were included in the analysis. Of these 94 (53.1%) achieved only mTICI-2B reperfusion, 16/94 (17.0%) patients achieved excellent functional outcomes at 3 months and 26 (27.7%) had hyperdensity on follow-up computed tomography (CT). On univariate analysis, the presence of VLLC was inversely associated with excellent functional outcomes at 3 months and positively associated with mortality in patients with mTICI-2B reperfusion. On multivariate analysis VLLC was inversely associated with excellent outcomes (odds ratio 0.075, 95% confidence interval 0.007–0.765, P = 0.029) but not associated with mortality. The mTICI-2B grade may be further refined by secondary radiological markers. The VLLC sign is associated with the loss of excellent functional outcomes at 3 months. It is a simple sign to discriminate mTICI-2B into different grades but should be verified in larger populations from other centers.

Aneurysmal bone cysts (ABCs) of spine are conventionally treated with en-bloc resection or intralesional excision/curettage and reconstruction or filling of defects with bone cement. For the treatment of upper cervical ABCs, en-bloc resections are often not desirable considering the risk/benefit ratio while the risk of recurrence after intralesional excision is high. Hence, alternative management options are often necessary. We describe our clinical experience with one such treatment alternative-denosumab for the treatment of ABC of Atlas. We present a case of 16-year-old boy who presented with neck pain and restriction of neck movements. A large lytic lesion with multiple fluid–fluid interfaces involving vertebral arch of atlas was identified on further imaging. There was destruction of right lateral mass and the lesion was found encasing the right vertebral artery. Core needle biopsy confirmed the diagnosis of ABC. With no visible CT response after first session of intra-lesional injection of Calcitonin and Methylprednisolone, the patient was treated with denosumab (120 mg SC once-a-month) for a period of 12 months. His symptoms resolved within 7 months of onset of treatment and serial CT scans over 12-month treatment period showed complete ossification of the lesion. Further there was no evidence of recurrence at 12 months after completion of treatment. Our case report contributes to the accruing evidence on the effectiveness of denosumab for the treatment of spinal ABCs. However, long-term safety, risk of recurrence, optimal duration of treatment and consistency of denosumab are yet to be determined.

OBJECTIVEThe goal of this study was to assess the safety and feasibility of PulseRider, a novel endovascular stent, in the treatment of intracranial bifurcation aneurysms with wide necks. The authors present the initial results of the first 10 cases in which the PulseRider device was used.METHODSPatients whose aneurysms were intended to be treated with the PulseRider device at 2 institutions in the United Kingdom were identified prospectively. Patient demographics, procedural details, immediate neurological and clinical status, and immediate angiographic outcomes and 6-month clinical and imaging follow-up were recorded prospectively.RESULTSAt the end of the procedure, all 10 patients showed complete aneurysm occlusion (Raymond Class 1). There were no significant intraprocedural complications except for an occurrence of thromboembolism without clinical sequelae. There was no occurrence of aneurysm rupture or vessel dissection. At 6-month follow-up, 7 and 3 patients had modified Rankin Scale scores of 0 and 1, respectively. All 10 patients had stable aneurysm occlusion (Raymond Class 1) and daughter vessel intraluminal patency on 6-month follow-up catheter angiography.CONCLUSIONSThe authors' early experience with the PulseRider device demonstrates that it is a safe and effective adjunct in the treatment of bifurcation aneurysms with wide necks arising at the middle cerebral artery bifurcation, anterior cerebral artery, basilar apex, and carotid terminus. It works by providing a scaffold at the neck of the bifurcation aneurysm, enabling neck remodeling and coil support while maintaining parent vessel intraluminal patency. Early clinical and radiological follow-up showed good functional outcome and stable occlusion rates, respectively. Further data are needed to assess medium- and long-term outcomes with PulseRider.

A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0-2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.

Thrombectomy is a technique that has completely changed the management of acute stroke and current devices have shown that they can achieve upwards of 90% successful recanalization in selected cohorts. However, despite the effectiveness of these devices, there are a proportion of patients who still fail to achieve reperfusion of the affected vascular territory and an even larger portion of patients who have poor functional outcomes in spite of successful recanalization. There are no guidelines on how to treat these patients when such failures occur. In an effort to understand the underpinnings of how failed thrombectomy occurs, we extensively reviewed the current literature in clot properties, vascular access problems, stroke pathogenic mechanisms, embolic complications, failed procedures and pre-procedural imaging. A short summary of each of these contentious areas are provided and the current state of the art. Together these elements give a cohesive overview of the mechanisms of failed thrombectomy as well as the controversies facing the field. New techniques and devices can then be developed to minimize such factors during stroke thrombectomy.

Journal of stroke : JoS 21(1), 2-9 (2019). doi:10.5853/jos.2018.02026, Published by Korean Stroke Society, Seoul

Background and Purpose— In acute ischemic stroke, large early infarct size estimated by the Alberta Stroke Program Early CT Score (ASPECTS) is associated with poorer outcomes and is a relative contraindication for recanalization therapies. The state of the intracranial collateral circulation influences the functional outcome and may be a variable to consider before thrombolysis. We evaluated the prognostic effect of the collateral circulation in patients with thrombolyzed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS. Materials and Methods— Patients with anterior circulation acute ischemic stroke who received a computed tomographic angiogram and subsequent treatment with intravenous tissue-type plasminogen activator from 2010 to 2013 were studied. Two independent neuroradiologists determined their ASPECTS. We stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS≤7 points) and small volume infarcts (ASPECTS 8–10). In addition, we evaluated a third group with very large volume infarcts (ASPECTS≤5 points). We then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS-collaterals grading systems of the computed tomographic angiogram intracranial collaterals. Good outcomes were defined by modified Rankin Scale score of 0 to 2 at 3 months. Results— A total of 300 patients were included in the final analysis. For patients with very large volume infarcts (ASPECTS≤5 points), univariable analysis showed that younger age, male sex, lower National Institute of Health Stroke Scale (NIHSS), lower systolic blood pressure, and good collaterals by Maas, Tan, or ASPECTS-collaterals grading were predictors of good outcomes. On multivariate analysis, younger age (odds ratio, 0.93; 95% confidence interval, 0.89–0.97; P =0.002) and good collaterals by ASPECTS-collaterals system (odds ratio, 1.34; 95% confidence interval, 1.15–1.57; P Conclusions— In patients with large and very large volume infarcts, good collaterals as measured by the ASPECTS-collaterals system is associated with improved outcomes and can help select patients for intravenous thrombolysis.

Background and Purpose— We assessed the feasibility of obtaining diagnostic quality images of the heart and thoracic aorta by extending the z axis coverage of a non–ECG-gated computed tomographic angiogram performed in the primary evaluation of acute stroke without increasing the contrast dose. Methods— Twenty consecutive patients with acute ischemic stroke within the 4.5 hours of symptom onset were prospectively recruited. We increased the longitudinal coverage to the domes of the diaphragm to include the heart. Contrast administration (Omnipaque 350) remained unchanged (injected at 3–4 mL/s; total 60–80 mL, triggered by bolus tracking). Images of the heart and aorta, reconstructed at 5 mm slice thickness in 3 orthogonal planes, were read by a radiologist and cardiologist, findings conveyed to the treating neurologist, and correlated with the transthoracic or transesophageal echocardiogram performed within the next 24 hours. Results— Of 20 patients studied, 3 (15%) had abnormal findings: a left ventricular thrombus, a Stanford type A aortic dissection, and a thrombus of the left atrial appendage. Both thrombi were confirmed by transesophageal echocardiography, and anticoagulation was started urgently the following day. None of the patients developed contrast-induced nephropathy on follow-up. The radiation dose was slightly increased from a mean of 4.26 mSV (range, 3.88–4.70 mSV) to 5.17 (range, 3.95 to 6.25 mSV). Conclusions— Including the heart and ascending aorta in a routine non–ECG-gated computed tomographic angiogram enhances an existing imaging modality, with no increased incidence of contrast-induced nephropathy and minimal increase in radiation dose. This may help in the detection of high-risk cardiac and aortic sources of embolism in acute stroke patients.

Background and Purpose— Radiological findings play an essential role in therapeutic decision making and prognostication in acute ischemic stroke (AIS). The Boston Acute Stroke Imaging Scale (BASIS) and Middle Cerebral Artery-BASIS (M1-BASIS) methodologies are rapid purely radiological instruments and easily applicable for patients with AIS. We validated these methods in patients with AIS treated with intravenous tissue-type plasminogen activator. Methods— For BASIS, patients were labeled as having major stroke if there was occlusion of distal internal carotid artery, proximal (both M1 and M2 segments) of middle cerebral artery or the basilar artery, or an Alberta Stroke Program Early CT Score ≤7. M1-BASIS differs from BASIS by classifying AIS patients with M2 occlusion as a minor stroke. We evaluated these classification systems for predicting functional outcomes (modified Rankin Scale score 0–1) at 3 months. Results— Two hundred sixty-five consecutive AIS patients treated with intravenous tissue-type plasminogen activator were included. On multivariate analysis, younger age (odds ratio, 1.039, 95% confidence interval, 1.009–1.070; P =0.011), lower National Institutes of Health Stroke Scale score (odds ratio, 1.140; 95% confidence interval, 1.073–1.210; P P =0.039) were independent predictors of good functional outcome. When compared with National Institutes of Health Stroke Scale, the receiver operating characteristic curves for both BASIS (area under the curve, 0.721) and M1-BASIS (area under the curve, 0.795) correlated well with clinical severity scores. M1-BASIS has an additive effect with the National Institutes of Health Stroke Scale score to predict good outcomes. Conclusions— The purely radiological M1-BASIS correlates well with the clinical severity of stroke and can be a reliable prognostication tool in thrombolyzed AIS patients. This system might find an important place in the current era of telestroke.

AIM: To define the role of computed tomography (CT) in identifying and classifying the imaging patterns of diagnostic value in Kimura's disease of the head and neck. METHODS: A retrospective study was undertaken comprising 13 patients with histopathological evidence of Kimura's disease. The patients' clinical and pathological records were reviewed against a detailed analysis of their CT images performed from the base of the skull to the arch of the aorta. RESULTS: Both well-defined, nodular masses, as well as ill-defined plaque-like infiltrative masses were seen in the subcutaneous tissue of the head and neck region. All patients had lesions adjacent to the major salivary glands. The parotid gland was affected in 10 of the 13 cases and the submandibular gland was affected in the rest. Contrast enhancement was variable. More than half of the cases had associated lymphadenopathy. Some of them showed atrophy of the skin and subcutaneous fat overlying the subcutaneous masses. Blood eosinophilia was a consistent feature in all the cases. CONCLUSION: The patterns of distribution, morphology, and enhancement of the lesions in Kimura's disease that can be demonstrated at CT, enables a confident, non-invasive diagnosis of this condition, in an appropriate clinical context.

e14507 Background: Regorafenib, an oral multikinase inhibitor of VEGFR2/3, PDGFRb, KIT, FGFR, RET, RAF and TIE2, is efficacious in refractory mCRC but its mechanism of action is unclear and predictive biomarkers are lacking. Methods: We assessed tumor and circulatory biomarkers in a phase 2 study of regorafenib in refractory mCRC patients. Regorafenib was administered orally at 160mg/d for 3 out of 4 weeks. Post cycle 2 response was assessed by RECIST 1.1. Subjects were scheduled for FDG PET-CT scans (pre + D15) and paired core needle tumor biopsies for IHC analysis (pre + D21) in cycle 1. Archival tumor mutations were evaluated using Sequenom MassARRAY OncoCarta Panel V1.0 assay. Results: 35 patients were treated; 49% received > 4 prior therapies and 43% had prior bevacizumab. Median PFS was 3.45 mths (95% CI: 3.40-3.49), ORR was 3% and disease control rate [DCR] (PR + SD at 8 wks) was 57%. Early PET responses (EORTC criteria) were seen in 49%, but did not predict for DCR (p=1.0). Fatigue, hand foot skin reaction (HFSR), voice change and diarrhea occurred in > 30% of subjects. Grade 3-5 toxicities occurred in 46%, the commonest being HFSR and rash (17% each). Median relative dose intensity was 92%; 43% required > 1 dose reduction, 60% required > 1 dose interruption. KRAS (29%), BRAF (9%), EGFR (9%), NRAS (6%) KIT (3%), PIK3CA (3%), PDGFRA (3%) and CDK (3%) mutations were detected in archival tumors. None predicted for ORR or DCR; PFS was identical in KRAS mutant vs wt patients (3.45 mths, p=0.39) and similar in BRAF mutant vs wt patients (3.48 vs 3.45 mths, p=0.10). The patient with the longest PFS (12.6 mths) had a BRAF mutation. Amongst the 10 paired tumor samples available, IHC markers upregulated in >50% cases were pMEK, pERK, pJun and pJNK, whilst those downregulated/ unchanged in >50% were pKIT, pVEGFR2, CD31 [vascular endothelial cells (ECs)] and podoplanin (lymphatic ECs). The greatest change was observed in podoplanin expression, corresponding to a 60% reduction in lymphatic vessel density. Conclusions: FDG-PET responses in cycle 1 did not predict for regorafenib clinical benefit in mCRC patients. Targeting lymphatic/vascular ECs in the tumor microenvironment may be a more significant antitumor mechanism of regorafenib than MAP kinase pathway inhibition. Clinical trial information: NCT01189903.

Background Regorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events. We aim to elucidate the pharmacodynamic effects of regorafenib in metastatic colorectal cancer and discover potential biomarkers that may predict clinical benefit. Methods Patients with metastatic colorectal adenocarcinoma refractory to standard therapy with tumours amenable to biopsy were eligible for the study. Regorafenib was administered orally at 160 mg daily for 3 out of 4 weeks with tumour assessment every 2 cycles. Metabolic response was assessed by FDG PET-CT scans (pre-treatment and day 15); paired tumour biopsies (pre-treatment and day 21 post-treatment) were sampled for immunohistochemistry and proteomic profiling analyses. Plasma circulating cell free DNA was quantified serially before and after treatment. Results There were 2(6%) partial responses out of 35 patients, and 8(23%) patients had stable disease for more than 7 months. Adverse event profile was similar to reported data. Recurrent somatic mutations in K-RAS, PIK3CA and BRAF were detected in plasma circulating cell free DNA in 14 patients; some mutations were not found in archival tumour. Total plasma circulating cell free DNA inversely correlated with progression free survival (PFS), and presence of KRAS mutations associated with shorter PFS. Immunohistochemistry of pre- and post- treatment biopsies showed majority of patients had downregulation of phosphorylated-VEGFR2, podoplanin, phosphorylated-AKT, Ki-67 and upregulation of the MEK-ERK axis, phosphorylated-C-MET, phosphorylated-SRC, phosphorylated-STAT3 and phosphorylated-JUN. Proteomic analysis of fine needle tumour aspirates showed down-regulation of PI3K was associated with longer PFS. Conclusion Plasma circulating cell free DNA may yield potential predictive biomarkers of regorafenib treatment. Downregulation of the PI3K-AKT axis may be an important predictor of clinical benefit. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0405-4) contains supplementary material, which is available to authorized users.