Phenotypes of Chronic Covert Brain Infarction in Patients With First-Ever Ischemic Stroke: A Cohort Study.

BACKGROUND AND PURPOSE: The aim of this study was to assess the rate of chronic covert brain infarctions (CBIs) in patients with acute ischemic stroke (AIS) and to describe their phenotypes and diagnostic value. METHODS: This is a single-center cohort study including 1546 consecutive patients with first-ever AIS on magnetic resonance imaging imaging from January 2015 to December 2017. The main study outcomes were CBI phenotypes, their relative frequencies, location, and association with vascular risk factors. RESULTS: Any CBI was present in 574/1546 (37% [95% CI, 35%-40%]) of patients with a total of 950 CBI lesions. The most frequent locations of CBI were cerebellar in 295/950 (31%), subcortical supratentorial in 292/950 (31%), and cortical in 213/950 (24%). CBI phenotypes included lacunes (49%), combined gray and white matter lesions (30%), gray matter lesions (13%), and large subcortical infarcts (7%). Vascular risk profile and white matter hyperintensities severity (19% if no white matter hyperintensity, 63% in severe white matter hyperintensity, P<0.001) were associated with presence of any CBI. Atrial fibrillation was associated with cortical lesions (adjusted odds ratio, 2.032 [95% CI, 1.041-3.967]). Median National Institutes of Health Stroke Scale scores on admission were higher in patients with an embolic CBI phenotype (median National Institutes of Health Stroke Scale, 5 [2-10], P=0.025). CONCLUSIONS: CBIs were present in more than a third of patients with first AIS. Their location and phenotypes as determined by MRI were different from previous studies using computed tomography imaging. Among patients suffering from AIS, those with additional CBI represent a vascular high-risk subgroup and the association of different phenotypes of CBIs with differing risk factor profiles potentially points toward discriminative AIS etiologies.

Repeated Intravenous Thrombolysis for Early Recurrent Stroke: Challenging the Exclusion Criterion.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) within 4.5 hours from symptom onset improves functional outcome in patients with acute ischemic stroke. Its use in patients with previous stroke within the preceding 3 months is contraindicated because of the assumed higher risk of intracranial hemorrhage. In addition, tissue-type plasminogen activator may itself promote neurotoxicity and blood-brain barrier disruption. However, safety and effectiveness of repeated IVT is essentially unknown in patients with early (<3 months) recurrent stroke (ERS), because they were excluded from thrombolysis trials. This article reports the largest case series of repeated IVT in ERS. METHODS: We reviewed databases of prospectively collected patient data of 8 European stroke centers for the presence of patients with ERS, who received IVT for both the index stroke and ERS. Demographics, clinical and radiological data, bleeding complications, and functional outcome were analyzed. RESULTS: We identified 19 subjects with repeated IVT in ERS. Mean age was 68±12 years, and 37% of them were female. Median interthrombolysis interval was 30 days (interquartile range, 13-50). Functional independence (modified Rankin scale score ≤2) was achieved in 79% of patients after the first and in 47.4% after repeated IV tissue-type plasminogen activator, respectively. There was no symptomatic intracranial hemorrhage. Median final infarct volume after the first IVT was 1.5 cm(3) (interquartile range, 0.5-3.1). CONCLUSIONS: Patients with small infarct volumes and robust clinical improvement might be considered for repeated IVT within 3 months. Studies following strict protocols and larger registries incorporating these patients might serve to identify selection criteria for the safe use of repeated IVT in ERS.

Occlusion Location of Middle Cerebral Artery Stroke and Outcome after Endovascular Treatment.

BACKGROUND: The aim of this study was to analyze the influence of the location of middle cerebral artery (MCA) occlusion on recanalization, complications and outcome after endovascular therapy. METHODS: Four-hundred sixty-four patients with acute MCA occlusions were treated with endovascular therapy. RESULTS: Two-hundred ninety-three patients had M1 occlusions, 116 had M2, and 55 had M3/4 occlusions. Partial or complete recanalization was more frequently achieved in M1 (76.8%) than in M2 (59.1%) or M3/4 (47.3%, p < 0.001) occlusions, but favorable outcome (modified Rankin Scale 0-2) was less frequent in M1 (50.9%) than M2 (63.7%) or M3/4 (72.7%, p = 0.018) occlusions. Symptomatic intracerebral hemorrhage (ICH) did not differ between occlusion sites, but asymptomatic ICH was more common in M1 (22.6%) than in M2 occlusions (8.6%, p = 0.003). Recanalization was associated with favorable outcome in M1 (p < 0.001) and proximal M2 (p = 0.003) but not in distal M2 or M3/4 occlusions. CONCLUSIONS: Recanalization with endovascular therapy was more frequently achieved in patients with proximal than distal MCA occlusions, but recanalization was associated with favorable outcome only in M1 and proximal M2 occlusions. Outcome was better with distal than proximal occlusions. This study shows that recanalization can be used as a surrogate marker for clinical outcome only in patients with proximal occlusions.

Preexisting cerebral microbleeds on susceptibility-weighted magnetic resonance imaging and post-thrombolysis bleeding risk in 392 patients.

BACKGROUND AND PURPOSE: The question whether cerebral microbleeds (CMBs) visible on MRI in acute stroke increase the risk for intracerebral hemorrhages (ICHs) or worse outcome after thrombolysis is unresolved. The aim of this study was to analyze the impact of CMB detected with pretreatment susceptibility-weighted MRI on ICH occurrence and outcome. METHODS: From 2010 to 2013 we treated 724 patients with intravenous thrombolysis, endovascular therapy, or intravenous thrombolysis followed by endovascular therapy. A total of 392 of the 724 patients were examined with susceptibility-weighted MRI before treatment. CMBs were rated retrospectively. Multivariable regression analysis was used to determine the impact of CMB on ICH and outcome. RESULTS: Of 392 patients, 174 were treated with intravenous thrombolysis, 150 with endovascular therapy, and 68 with intravenous thrombolysis followed by endovascular therapy. CMBs were detected in 79 (20.2%) patients. Symptomatic ICH occurred in 21 (5.4%) and asymptomatic in 75 (19.1%) patients, thereof 61 (15.6%) bleedings within and 35 (8.9%) outside the infarct. Neither the existence of CMB, their burden, predominant location nor their presumed pathogenesis influenced the risk for symptomatic or asymptomatic ICH. A higher CMB burden marginally increased the risk for ICH outside the infarct (P=0.048; odds ratio, 1.004; 95% confidence interval, 1.000-1.008). CONCLUSIONS: CMB detected on pretreatment susceptibility-weighted MRI did not increase the risk for ICH or worsen outcome, even when CMB burden, predominant location, or presumed pathogenesis was considered. There was only a small increased risk for ICH outside the infarct with increasing CMB burden that does not advise against thrombolysis in such patients.

Intracranial Atherosclerotic Stenoses: Pathophysiology, Epidemiology, Risk Factors and Current Therapy Options.

Intracranial atherosclerotic stenoses (ICAS) are one of the most common causes of first and recurrent cerebrovascular ischaemic events worldwide, with highest prevalence in Asian, Hispanic and African populations. Clinical trials have improved the understanding of epidemiology, risk factors and imaging characteristics of patients with ICAS. Current therapeutic approaches concerning these patients include management of risk factors, best medical therapy, potentially endovascular and rarely surgical therapy. In our review, we elucidate the current epidemiology and evidence in evaluation of risk factors and therapeutic options for providing favourable outcome for patients with ICAS.

Calcified vessels in the brain are one of the most common causes of first or recurrent ischaemic stroke or transient ischaemic attack worldwide, with highest occurrence in Asian, Hispanic and African populations. Clinical trials have improved the understanding of this particular disease. Current therapy includes management of risk factors, best medical therapy, potentially therapy with a wire and rarely surgical therapy. In our review, we elucidate current knowledge and recommendations.

Late seizures in cerebral venous thrombosis.

OBJECTIVE: To examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT. METHODS: We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS. RESULTS: We included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0-6.3), 123 patients (11%) experienced ≥1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25-35). Median time to first LS was 5 months (IQR 1-16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9-12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4-7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5-6.5), subdural hematoma (HR 2.3, 95% CI 1.1-4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1-3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS. CONCLUSION: During a median follow-up of 2 years, ≈1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS.

Clinical presentation, diagnostic findings and management of cerebral ischemic events in patients on treatment with non-vitamin K antagonist oral anticoagulants - A systematic review.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOAC) are equally or potentially superior in terms of effectiveness in the prevention of ischemic stroke and carry a lower associated risk of intracranial hemorrhage compared to Vitamin K antagonists. Nevertheless, ischemic strokes also occur in patients who are being treated with NOAC. In those particular patients, knowledge about the underlying stroke etiology, clinical presentation, acute management, and complication rates is scarce. OBJECTIVE: Systematic literature review to provide a comprehensive clinical overview in terms of presentation, laboratory, imaging parameters and outcomes of patients suffering from acute cerebral ischemic events (i.e. TIA and acute ischemic stroke) while on treatment with a NOAC. Only if available, comparison to VKA is presented which was not the primary focus of this analysis. DATA SOURCES: PubMed/MEDLINE, Scopus and EMBASE from January 1, 2006, to November 20, 2018. STUDY ELIGIBILITY CRITERIA: 52 studies providing detailed information on a total of 12247 patients were included. We excluded case reports and case series with less than five patients. STUDY APPRAISAL AND SYNTHESIS METHOD: We systematically assessed study quality using a bias tool and pooled consistent data. RESULTS: Existing data indicates milder stroke severity and smaller infarct size of acute ischemic stroke on treatment with NOAC compared to stroke occurrence on Vitamin K antagonists (VKA). Established risk factors for ischemic events also play a role in stroke while on NOACs, albeit the underlying etiology remains poorly understood. Intravenous thrombolysis and endovascular therapy seem to be safe and effective, but patient selection for recanalization therapies is challenging. LIMITATIONS: Limited quality of published data, duplicate cases, statistical issues of data pooling, possible incomplete retrieval of identified research and reporting bias might have limited our findings. CONCLUSIONS: Acute ischemic events despite treatment with NOAC therapy are insufficiently investigated. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO: CRD42018074853.

Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry.

BACKGROUND AND PURPOSE: In acute ischaemic stroke (AIS) of the anterior circulation (AC) treated with mechanical thrombectomy (MT), data point to a decline of treatment effect with increasing time from symptom onset to treatment. However, the magnitude of the decline will depend on the clinical setting and imaging selection used. The aims of this study were (1) to evaluate the clinical effect of time to reperfusion (TTR); and (2) to assess the safety and technical efficacy of MT according to strata of TTR. METHODS: Using the retrospective multicentre BEYOND-SWIFT registry data (ClinicalTrials.gov identifier: NCT03496064), we compared safety and efficacy of MT in 1461 patients between TTR strata of 0-180 min (n = 192), 180-360 min (n = 876) and >360 min (n = 393). Clinical effect of TTR was evaluated using multivariable logistic regression analyses adjusting for pre-specified confounders [adjusted odds ratios (aOR) and 95% confidence intervals (95% CI)]. Primary outcome was good functional outcome (modified Rankin Scale: mRS 0-2) at day 90. RESULTS: Every hour delay in TTR was a significant factor related to mRS 0-2 (aOR 0.933, 95% CI 0.887-0.981) with an estimated 1.5% decreased probability of good functional outcome per hour delay of reperfusion, and mRS 0-1 (aOR 0.929, 95% CI 0.877-0.985). Patients with late TTR had lower rates of successful and excellent reperfusion, higher complication rates and number of passes. CONCLUSIONS: TTR is an independent factor related to long-term functional outcome. With increasing TTR, interventional procedures become technically less effective. Efforts should be made to shorten TTR through optimized prehospital and in-hospital pathways.

Differentiating enhancing multiple sclerosis lesions, glioblastoma, and lymphoma with dynamic texture parameters analysis (DTPA): A feasibility study.

PURPOSE: MR-imaging hallmarks of glioblastoma (GB), cerebral lymphoma (CL), and demyelinating lesions are gadolinium (Gd) uptake due to blood-brain barrier disruption. Thus, initial diagnosis may be difficult based on conventional Gd-enhanced MRI alone. Here, the added value of a dynamic texture parameter analysis (DTPA) in the differentiation between these three entities is examined. DTPA is an in-house software tool that incorporates the analysis of quantitative texture parameters extracted from dynamic susceptibility contrast-enhanced (DSCE) images. METHODS: Twelve patients with multiple sclerosis (MS), 15 patients with GB, and five patients with CL were included. The image analysis method focuses on the DSCE image time series during bolus passage. Three time intervals were examined: inflow, outflow, and reperfusion time interval. Texture maps were computed. From the DSCE image series, mean, difference, standard deviation, and variance texture parameters were calculated and statistically analyzed and compared between the pathologies. RESULTS: The texture parameters of the original DSCE image series for mean, standard deviation, and variance showed the most significant differences (P-value between <0.00 and 0.05) between pathologies. Further, the texture parameters related to the standard deviation or variance (both associated with tissue heterogeneity) revealed the strongest discriminations between the pathologies. CONCLUSION: We conclude that dynamic perfusion texture parameters as assessed by the DTPA method allow discriminating MS, GB, and CL lesions during the first passage of contrast. DTPA used in combination with classification algorithms has the potential to find the most likely diagnosis given a postulated differential diagnosis.

Characterization of microcirculation in multiple sclerosis lesions by dynamic texture parameter analysis (DTPA).

OBJECTIVE: Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA), a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL), non-enhancing lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis (MS). METHODS: We investigated 18 patients with MS and clinical isolated syndrome (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. RESULTS: Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant differences in the DTPA texture maps were found during inflow (52 parameters), outflow (40 parameters) and reperfusion (62 parameters). The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. CONCLUSION: DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2-hypersignal, on a numeric scale allowing for a more subtle grading of MS-lesions.

Vascular diseases of the spinal cord: a review.

OPINION STATEMENT: • In acute spinal cord ischemia syndrome (ASCIS), treatment recommendations are derived from data of cerebral ischemic stroke, atherosclerotic vascular disease and acute spinal cord injury. Besides acute management, secondary prevention is of major importance. Pathologies affecting the aorta as well as underlying cerebrovascular conditions should be treated whenever possible.• ASCIS may occur after aortic surgery, less often after thoracic endovascular aortic repair (TEVAR). Protocols are proposed.• Acute spinal cord hemorrhage can be treated surgically and/or pharmacologically.• Symptomatic treatment in patients with a spinal cord lesion is of major importance. Depending on level and extension of the lesion, there is a risk for systemic and neurological complications, which may be life-threatening.• Each spinal vascular malformation is a unique lesion that needs an individualized treatment algorithm. In case of a symptomatic vascular malformation, endovascular intervention is the primary treatment option.• Spinal dural Arteriovenous fistula (AVF) may be treated endovascularly or surgically. If preoperative localization of the fistula is possible, surgery is feasible with a low complication rate. In comparison, endovascular approaches are less invasive.• Spinal AVM are rather treated endovascularly than surgically or in a stepwise multidisciplinary approach.• Symptomatic and exophytic spinal cavernous angiomas should be treated surgically. Deep spinal cavernous angiomas that are asymptomatic or only show mild symptoms can be observed.