Vladimir Rohan

Length of Occlusion Predicts Recanalization and Outcome After Intravenous Thrombolysis in Middle Cerebral Artery Stroke

Background and Purpose— The length of large vessel occlusion is considered a major factor for therapy in patients with ischemic stroke. We used 4D-CT angiography evaluation of middle cerebral artery occlusion in prediction of recanalization and favorable clinical outcome and after intravenous thrombolysis (IV-tPA). Methods— In 80 patients treated with IV-tPA for acute complete middle cerebral artery/M1 occlusion determined using CT angiography and temporal maximum intensity projection, calculated from 4D-CT angiography, the length of middle cerebral artery proximal stump, occlusion in M1 or M1 and M2 segment were measured. Univariate and multivariate analyses were performed to define independent predictors of successful recanalization after 24 hours and favorable outcome after 3 months. Results— The length of occlusion was measureable in all patients using temporal maximum intensity projection. Recanalization thrombolysis in myocardial infarction 2 to 3 was achieved in 37 individuals (46%). The extension to M2 segment as a category (odds ratio, 4.58; 95% confidence interval, 1.39–15.05; P=0.012) and the length of M1 segment occlusion (odds ratio, 0.82; 95% confidence interval, 0.73–0.92; P=0.0007) with an optimal cutoff value of 12 mm (sensitivity 0.67; specificity 0.71) were significant independent predictors of recanalization. Favorable outcome (modified Rankin scale 0–2) was achieved in 25 patients (31%), baseline National Institutes of Health Stroke Scale (odds ratio, 0.82; 95% confidence interval, 0.72–0.93; P=0.003) and the length of occlusion M1 in segment (odds ratio, 0.79; 95% confidence interval, 0.69–0.91; P=0.0008) with an optimal cutoff value of 11 mm (sensitivity 0.74; specificity 0.76) were significant independent predictors of favorable outcome. Conclusions— The length of middle cerebral artery occlusion is an independent predictor of successful IV-tPA treatment.

Isocitrate Dehydrogenase-1 Mutations as Prognostic Biomarker in Glioblastoma Multiforme Patients in West Bohemia

Introduction. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. Recent whole-genome studies revealed novel GBM prognostic biomarkers such as mutations in metabolic enzyme IDH—isocitrate dehydrogenases (IDH1 and IDH2). The distinctive mutation IDH1 R132H was uncovered to be a strong prognostic biomarker for glioma patients. We investigated the prognostic role of IDH1 R132H mutation in GBM patients in West Bohemia. Methods. The IDH1 R132H mutation was assessed by the RT-PCR in the tumor samples from 45 GBM patients treated in the Faculty Hospital in Pilsen and was correlated with the progression free and overall survival. Results. The IDH1 R132H mutation was identified in 20 from 44 GBM tumor samples (45.4%). The majority of mutated tumors were secondary GBMs (16 in 18, 89.9%). Low frequency of IDH1 mutations was observed in primary GBMs (4 in 26, 15.3%). Patients with IDH R132H mutation had longer PFS, 136 versus 51 days (P < 0.021, Wilcoxon), and OS, 270 versus 130 days (P < 0.024, Wilcoxon test). Summary. The prognostic value of IDH1 R132H mutation in GBM patients was verified. Patients with mutation had significantly longer PFS and OS than patients with wild-type IDH1 and suffered more likely from secondary GBMs.

Personalized approach to primary and secondary prevention of ischemic stroke.

Primary and secondary prevention of ischemic stroke represents a significant part of stroke management and health care. Although there are official guidelines concerning stroke management, new knowledge are introduced to them with a slight delay. This article provides an overview of current information on primary and secondary prevention of ischemic stroke. It summarizes information especially in the field of cardioembolic stroke, the use of new anticoagulants and the management of carotid stenosis based on the results of recent clinical studies. The optimal approach in stroke management is to follow these recommendations, to know new strategies and to apply an individual personalized approach in our clinical decisions.

Mechanical thrombectomy performs similarly in real world practice: a 2016 nationwide study from the Czech Republic

Background Randomized clinical trials have proven mechanical thrombectomy (MT) to be a highly effective and safe treatment in acute stroke. The purpose of this study was to compare neurothrombectomy data from the Czech Republic (CR) with data from the HERMES meta-analysis. Methods Available nationwide data for the CR from 2016 from the Safe Implementation of Treatments in Stroke–Thrombectomy (SITS-TBY) registry for patients with terminal internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusions were compared with data from HERMES. CR and HERMES patients were comparable in age, sex, and baseline National Institutes of Health Stroke Scale scores. Results From a total of 1053 MTs performed in the CR, 845 (80%) were reported in the SITS-TBY. From these, 604 (72%) were included in this study. Occlusion locations were as follows (CR vs HERMES): ICA 22% versus 21% (P=0.16), M1 MCA 62% versus 69% (P=0.004), and M2 MCA 16% versus 8% (P<0.0001). Intravenous thrombolysis was given to 76% versus 83% of patients, respectively (P=0.003). Median onset to reperfusion times were comparable: 232 versus 285 min, respectively (P=0.66). A modified Thrombolysis in Cerebral Infarction score of 2b/3 was achieved in 74% (433/584) versus 71% (390/549) of patients, respectively (OR 1.17, 95% CI 0.90–1.5, P=0.24). There was no statistically significant difference in the percentage of parenchymalhematoma type 2 (OR 1.12, 95% CI 0.66–1.90, P=0.68). A modified Rankin Scale score of 0–2 at 3 months was achieved in 48% (184/268) versus 46% (291/633) of patients, respectively (OR 0.92, 95% CI 0.71–1.18, P=0.48). Conclusions Data on efficacy, safety, and logistics of MT from the CR were similar to data from the HERMES collaboration.

Prolonged Corrected QT Interval as a Predictor of Clinical Outcome in Acute Ischemic Stroke

BACKGROUND This study aimed to investigate changes of corrected QT (QTc) interval during acute ischemic stroke and its correlation with high-sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP), neurological outcome, and 1-year mortality. METHODS We registered electrocardiogram in 69 patients immediately after admission to the intensive care unit and then after 24 and 48 hours. Computed tomography was performed on admission to determine brain infarct size and localization. Neurological outcome was assessed by modified Rankin scale (mRS) at discharge. RESULTS Forty-five (65.2%) patients had prolonged QTc at baseline; only 18 (26.1%) patients had prolonged QTc after 48 hours. Baseline QTc was not associated with neurological outcome (P = .27). However, prolonged QTc after 48 hours was associated with worse mRS at discharge (4.5 [4.0-6.0] versus 2.0 [1.0-3.0]; P < .0001). Patients who deceased during hospitalization (n = 7 [10.1%]) as compared with survivors had more frequently prolonged QTc after 48 hours (38.9 versus 0%; P < .0001), higher level of hsTnI (48.4 [36.1-75.0] versus 8.6 [3.4-26.5]; P = .003), and BNP (334 [224-866] versus 109 [30-190]; P = .014). In univariate analysis, 1-year mortality was associated with prolonged QTc after 48 hours, hsTnI, and BNP. In multivariate analysis, only BNP remained to be associated with 1-year mortality (odds ratio 3.41, 95% confidence interval 1.06-11.03). CONCLUSIONS QTc interval in patients with acute ischemic stroke is a dynamic parameter. Prolonged QTc after 48 hours, but not baseline QTc, correlated with neurological outcome and 1-year mortality. Patients with prolonged QTc had higher level of hsTnI.

Cerebrovascular diseases research database

Cerebrovascular diseases are one of the most common causes of death worldwide. In this paper, we analyze relationships in heterogeneous collaborating centres medical data to resolve a solution of this complex problem. Data mining is primarily based on clinical data, imaging examinations and therapeutic data stored in various data formats. The raw and mined data can be used by a registered medical doctors in the knowledge base for an evaluation of hypothesis or tests.

Intravenous Thrombolysis in Patients with Acute Ischemic Stroke after a Reversal of Dabigatran Anticoagulation with Idarucizumab: A Real-World Clinical Experience

BACKGROUND Intravenous thrombolysis (IVT) is contraindicated in patients with acute ischemic stroke (AIS) using oral anticoagulants. A specific human monoclonal antibody was introduced to reverse immediately the anticoagulation effect of the direct inhibitor of thrombin, dabigatran. Until now, mostly individual cases presenting with successful IVT after a reversal of dabigatran anticoagulation in patients with AIS were published. Thus, we aimed to report real-world data from clinical practice. METHODS Patients with AIS on dabigatran treated with IVT after antidote reversal were enrolled in the retrospective nationwide study. Neurological deficit was scored using the National Institutes of Health Stroke Scale (NIHSS) and 90-day clinical outcome using modified Rankin scale (mRS) with a score 0-2 for a good outcome. Intracerebral hemorrhage (ICH) was defined as a presence of any sign of bleeding on control imaging after IVT, and symptomatic intracerebral hemorrhage (SICH) was assessed according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. RESULTS In total, 13 patients (7 men, mean age 70.0 ± 9.1 years) with a median NIHSS admission score of 7 points were analyzed. Of these patients, 61.5% used 2 × 150 mg of dabigatran daily. Antidote was administrated 427 ± 235 minutes after the last intake of dabigatran, with a mean activated prothrombin time of 38.1 ± 27.8 seconds and a mean thrombin time of 72.2 ± 56.1 seconds. Of the 13 patients, 2 had ICH and 1 had SICH, and no other bleeding complications were observed after IVT. Of the total number of patients, 76.9% had a good 3-month clinical outcome and 3 patients (23.1%) died. Recurrent ischemic stroke occurred in 2 patients (15.4%). CONCLUSION The data presented in the study support the safety and efficacy of IVT after the reversal of the anticoagulation effect of dabigatran with antidote in a real-world clinical practice.

Atrioesophageal fistula: a rare cause of brain embolization

Radiofrequency catheter ablation is an important part of the treatment algorithm in patients with highly symptomatic atrial fibrillation. The most common strategy involves isolation of the pulmonary veins alone or in combination with additional ablation. Isolation of the pulmonary veins is based on the application of radiofrequency energy direct to the left atrium (to the ostia of pulmonary veins) to achieve complete electrical isolation of the pulmonary veins with minimal damage to the surrounding tissue. The treatment brings low risk of complications which, however, can be life-threatening—cardiac tamponade (1.31%), pseudoaneurysm, arteriovenous fistula (1.5%), pulmonary vein stenosis (1.3%), and phrenic nerve palsy (0.17%). Rare but serious complication is the formation of atrioesophageal fistula (AEF)—incidence 0.1–0.25%. Mortality exceeds 80%. Only a few dozens of cases have been documented worldwide. Case report

The application of personalized medicine in neurooncology

Primary brain tumors form an important public health problem. There were more than 66,000 cases diagnosed in the US in 2012 with 13,700 deaths. The most malignant primary brain tumor in adults - Glioblastoma multiforme (GBM) - is extremely aggressive and invasive cancer, difficult to surgery with high resistance to standard radiotherapy and chemotherapy. The median survival of patient with GBM is 12.1 – 14.6 months and only 3-5% of patients survive longer than 3 years. There is an urgent need for further progress in neurooncology in the area of tumor early diagnosis, accurate characterization and more efficient treatment. The unprecedented progress of recent years in all omics disciplines such as genomics, transcriptomics, proteomics and others together with the improvements of bioinformatics technologies provides new opportunities in current brain cancer research. The human genome was fully sequenced and the improvements of sequencing methods have lately permitted genome-wide association studies in human cancers including primary brain tumors. The new milestones of oncogenesis - abnormalities in signaling pathways, tumor microenvironment, pathological angiogenesis, cancer metabolism and others – were uncovered over the past decade. Currently some novel molecular biomarkers in neurooncology are emerging that could be used as a prognostic and predictive factor of the disease. For glioblastoma multiforme the most promising biomarker, promoter methylation status of the MGMT gene, helps to predict the tumor response to standard chemotherapy with temozolomide. For all astrocytic tumors, there is a strong prognostic effect of mutations in the fundamental metabolic enzymes - Isocitrate dehydrogenases 1 and 2. Also the epigenetic changes of cancer genome, glioma cytosine-guanine island methylator phenotype, show promise like the prognostic biomarker. For oligodendrogliomas, the most promising predictive biomarker in relation to the standard PCV chemotherapy treatment is the loss of 1p/19q due to an unbalanced chromosomal translocation. There are many other potential markers for primary brain tumors in research, such as the amount of CD 133 positive cancer „stem“ cells, small non-coding microRNA’s or tumors gene expression profiles. With the discovery of novel molecular prognostic and predictive markers for various brain tumors, the therapy goal is rapidly changing from treating a class of tumors to the individual therapy plan for each patient according to the molecular characterization of the actual tumor, the real philosophy of personalized medicine. Supported by Ministry of Health, Czech Republic - conceptual development of research organization (Faculty Hospital Pilsen - FNPl, 00669806) and by the project ED2.1.00/03.0076 from European Regional Development Fund.

Stroke care in West Bohemia – personalised medicine approach

Cerebrovascular disease is the third main cause of death and the leading cause of disablement in the Czech Republic. The incidence of stroke is higher than in Western European countries and is one of causes of lower average age in this country. The data of 15880 stroke patients who entered into the IKTA stroke register from 13 Czech stroke centres in the year 2010 and 2011 indicates higher proportion of stroke recurrence and unfavourable patient risk profile than in other Western European countries. Three major risk factors well–defined are arterial hypertension (identified in 86.2% of patients), dyslipidemia (58.2%) and diabetes mellitus (34.9% of stroke patients). Three or more risk factors were found in 80.7% of stroke patients. The incidence of vascular risk factors in stroke patients is significantly higher than stated in the literature and this unfavourable risk profile may be the main cause of the high incidence of stroke and its recurrence in Czech Republic. Stroke is a typical heterogeneous entity. In April 2010 the Ministry of Health published a document “Cerebrovascular Care in the Czech Republic, Constitution of Stroke Centres”. 11 Complex Cerebrovascular Centres and 23 Cerebrovascular Centres covering the whole area of the Czech Republic were constituted with intension to admit, diagnose and, if necessary, treat all new stroke patients, who had been formerly treated in the departments of internal medicine of any hospitals in the country. The aim is to provide complex, optimal and personalised care in acute phase of stroke, provide early rehabilitation and provide or propose optimal second prevention. Faculty Hospital Pilsen incorporates a long-term experience with stroke care and is one of two hospitals where patients with ischaemic stroke were first treated with intravenous thrombolysis in our country. The stroke care is coordinated by the Department of Neurology with its Stroke Unit and Stroke Team. The cooperation with neuroradiology, neurosurgery, cardiology, biochemical and immunoanalytic laboratories, pathology, genetics and some other specialities in Faculty Hospital and in Faculty of Medicine in Pilsen of Charles University in Prague is well established as well as the cooperation with Emergency Medical Service. Due to these facts West Bohemia region with 589 thousands of habitants has only one Complex Cerebrovascular Centre and no one or two smaller Cerebrovascular Centres as is usual in other regions. The advantage of this situation is the concentration of all stroke patients into the best equipped facility. Due to this fact stroke patients in West Bohemia are well diagnosed and treated. Exact data (numbers of thrombolytic, neurosurgical therapy, neuroradiological interventions and their proportion to all stroke patients) are presented. Special research project “Study of Variety Stroke Biomarkers in Acute Stroke Patients in the Context of Personalised Medicine“, supported by Czech Ministry of Health is being solved in our centre from the year 2011. Its main goal is to test the effectiveness of variety of stroke biomarkers and implement them into the personalised stroke care. Supported by Ministry of Health, Czech Republic - conceptual development of research organization (Faculty Hospital Pilsen - FNPl, 00669806) and by the project ED2.1.00/03.0076 from European Regional Development Fund.