Stephan P. Kloska

Anticoagulant Reversal, Blood Pressure Levels, and Anticoagulant Resumption in Patients With Anticoagulation-Related Intracerebral Hemorrhage

IMPORTANCE Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH). OBJECTIVE To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption. EXPOSURES Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment. MAIN OUTCOMES AND MEASURES Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome. RESULTS Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). CONCLUSIONS AND RELEVANCE Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01829581.

Flat Detector CT in the Evaluation of Brain Parenchyma, Intracranial Vasculature, and Cerebral Blood Volume: A Pilot Study in Patients with Acute Symptoms of Cerebral Ischemia

BACKGROUND AND PURPOSE: The viability of both brain parenchyma and vascular anatomy is important in estimating the risk and potential benefit of revascularization in patients with acute cerebral ischemia. We tested the hypothesis that when used in conjunction with IV contrast, FD-CT imaging would provide both anatomic and physiologic information that would correlate well with that obtained by using standard multisection CT techniques. MATERIALS AND METHODS: Imaging of brain parenchyma (FD-CT), cerebral vasculature (FD-CTA), and cerebral blood volume (FD-CBV) was performed in 10 patients. All patients also underwent conventional multisection CT, CTA, CTP (including CBV, CTP-CBV), and conventional catheter angiography. Correlation of the corresponding images was performed by 2 experienced neuroradiologists. RESULTS: There was good correlation of the CBV color maps and absolute values between FD-CBV and CTP-CBV (correlation coefficient, 0.72; P < .001). The Bland-Altman test showed a mean difference of CBV values between FD-CT and CTP-CBV of 0.04 ± 0.55 mL/100 mL. All vascular lesions identified with standard CTA were also visualized with FD-CTA. Visualization of brain parenchyma by using FD-CT was poor compared with that obtained by using standard CT. CONCLUSIONS: Both imaging of the cerebral vasculature and measurements of CBV by using FD-CT are feasible. The resulting vascular images and CBV measurements compared well with ones made by using standard CT techniques. The ability to measure CBV and also visualize cerebral vasculature in the angiography suite may offer significant advantages in the management of patients. FD-CT is not yet equivalent to CT for imaging of brain parenchyma.

Acute stroke magnetic resonance imaging: current status and future perspective

Cerebral stroke is one of the most frequent causes of permanent disability or death in the western world and a major burden in healthcare system. The major portion is caused by acute ischemia due to cerebral artery occlusion by a clot. The minority of strokes is related to intracerebral hemorrhage or other sources. To limit the permanent disability in ischemic stroke patients resulting from irreversible infarction of ischemic brain tissue, major efforts were made in the last decade. To extend the time window for thrombolysis, which is the only approved therapy, several imaging parameters in computed tomography and magnetic resonance imaging (MRI) have been investigated. However, the current guidelines neglect the fact that the portion of potentially salvageable ischemic tissue (penumbra) is not dependent on the time window but the individual collateral blood flow. Within the last years, the differentiation of infarct core and penumbra with MRI using diffusion-weighted images (DWI) and perfusion imaging (PI) with parameter maps was established. Current trials transform these technical advances to a redefined patient selection based on physiological parameters determined by MRI. This review article presents the current status of MRI for acute stroke imaging. A special focus is the ischemic stroke. In dependence on the pathophysiology of cerebral ischemia, the basic principle and diagnostic value of different MRI sequences are illustrated. MRI techniques for imaging of the main differential diagnoses of ischemic stroke are mentioned. Moreover, perspectives of MRI for imaging-based acute stroke treatment as well as monitoring of restorative stroke therapy from recent trials are discussed.

Feasibility of Cerebral Blood Volume Mapping by Flat Panel Detector CT in the Angiography Suite: First Experience in Patients with Acute Middle Cerebral Artery Occlusions

Because of the potential benefits of flat panel CT in assessing perfusion and the brain parenchyma, these investigators correlated studies with multisection and perfusion CT. All 4 techniques were used to study 16 patients with MCA occlusions posttreatment. There was a high correlation for CBV obtained with both flat panel and standard techniques. The authors concluded that this new flat panel CT application allows assessment of CBV in acute stroke patients. Their initial results indicated that these measurements may predict final infarct volume. The ability to assess this key parameter of cerebral perfusion within the angiographic suite may improve the management of these patients. BACKGROUND AND PURPOSE: A new FPCT application offers the possibility of perfusion (FPCT CBV) and parenchymal (FPCT) imaging within the angiography suite. We tested the hypothesis that findings in FPCT CBV and FPCT would correlate with those obtained using MSCT and PCT. MATERIALS AND METHODS: In 16 patients with acute MCA occlusion, FPCT CBV was performed immediately posttreatment. The volume of tissue having abnormal CBV values was determined by FPCT CBV and PCT images. Stroke volume on follow-up MSCT was determined, CBV values in the effected parenchyma were measured, and FPCT images were reviewed. RESULTS: In 6 cases, we found a FPCT CBV value identical or higher (hyperemia) in comparison with the contralateral side. In 10 cases, we found CBV lesions with values lower (oligemia) than the contralateral brain tissue. We found a high correlation of CBV lesion volume on FPCT CBV images to stroke volume on follow-up MSCT (r = 0.9, P < .05) in the oligemia group. Absolute FPCT CBV and PCT CBV values were comparable and showed good correlation (r = 0.9, P < .05). In 8 patients, contrast medium extravasation was visible. CONCLUSIONS: The new FPCT application allows assessment of CBV in acute stroke patients. Our initial results indicate that these measurements may predict final infarct volume. The ability to assess this key parameter of cerebral perfusion within the angiographic suite may improve the management of these patients.

Optimized intravenous Flat Detector CT for non-invasive visualization of intracranial stents: first results

ObjectiveAs stents for treating intracranial atherosclerotic stenosis may develop in-stent re-stenosis (ISR) in up to 30%, follow-up imaging is mandatory. Residual stenosis (RS) is not rare. We evaluated an optimised Flat Detector CT protocol with intravenous contrast material application (i.v. FD-CTA) for non-invasive follow-up.MethodsIn 12 patients with intracranial stents, follow-up imaging was performed using i.v. FD-CTA. MPR, subtracted MIP and VRT reconstructions were used to correlate to intra-arterial angiography (DSA). Two neuroradiologists evaluated the images in anonymous consensus reading and calculated the ISR or RS. Correlation coefficients and a Wilcoxon test were used for statistical analysis.ResultsIn 4 patients, no stenosis was detected. In 6 patients RS and in two cases ISR by intima hyperplasia perfectly visible on MPR reconstructions of i.v. FD-CTA were detected. Wilcoxon’s test showed no significant differences between the methods (p > 0.05). We found a high correlation with coefficients of the pairs DSA/ FD-CT MIP r = 0.91, DSA/ FD-CT MPR r = 0.82 and FD-CT MIP/ FD-CT MPR r = 0.8.ConclusionIntravenous FD-CTA could clearly visualise the stent and the lumen, allowing ISR or RS to be recognised. FD-CTA provides a non-invasive depiction of intracranial stents and might replace DSA for non-invasive follow-up imaging.

Hyponatremia Is an Independent Predictor of In-Hospital Mortality in Spontaneous Intracerebral Hemorrhage

Background and Purpose— Hyponatremia is the most frequent electrolyte disturbance in critical care. Across various disciplines, hyponatremia is associated with increased mortality and longer hospital stay, yet in intracerebral hemorrhage (ICH) no data are available. This the first study that investigated the prevalence and clinical associations of hyponatremia in patients with ICH. Methods— This observational study included all consecutive spontaneous ICH patients (n=464) admitted during a 5-year period to the Department of Neurology. Patient characteristics, in-hospital measures, mortality, and functional outcome (90 days and 1 year) were analyzed to determine the effects of hyponatremia (Na <135 mEq/L). Multivariable regression analyses were calculated for factors associated with hyponatremia and predictors of in-hospital mortality. Results— The prevalence of hyponatremia on hospital admission was 15.6% (n=66). Normonatremia was achieved and maintained in almost all hyponatremia patients <48 hours. In-hospital mortality was roughly doubled in hyponatremia compared with nonhyponatremia patients (40.9%; n=27 versus 21.1%; n=75), translating into a 2.5-fold increased odds ratio (P<0.001). Multivariable analyses identified hyponatremia as an independent predictor of in-hospital mortality (odds ratio, 2.2; 95% confidence interval, 1.05–4.62; P=0.037). Within 90 days after ICH, hyponatremia patients surviving hospital stay were also at greater risk of death (odds ratio, 4.8; 95% confidence interval, 2.1–10.6; P<0.001); thereafter, mortality rates were similar. Conclusions— Hyponatremia was identified as an independent predictor of in-hospital mortality with a fairly high prevalence in spontaneous ICH patients. The presence of hyponatremia at hospital admission is related to an increased short-term mortality in patients surviving acute care, possibly reflecting a preexisting condition that is linked to worse outcome due to greater comorbidity. Correction of hyponatremia does not seem to compensate its influence on mortality, which strongly warrants future research.

Predictors for good functional outcome after neurocritical care

IntroductionThere are only limited data on the long-term outcome of patients receiving specialized neurocritical care. In this study we analyzed survival, long-term mortality and functional outcome after neurocritical care and determined predictors for good functional outcome.MethodsWe retrospectively investigated 796 consecutive patients admitted to a non-surgical neurologic intensive care unit over a period of two years (2006 and 2007). Demographic and clinical parameters were analyzed. Depending on the diagnosis, we grouped patients according to their diseases (cerebral ischemia, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), meningitis/encephalitis, epilepsy, Guillain-Barré syndrome (GBS) and myasthenia gravis (MG), neurodegenerative diseases and encephalopathy, cerebral neoplasm and intoxication). Clinical parameters, mortality and functional outcome of all treated patients were analyzed. Functional outcome (using the modified Rankin Scale, mRS) one year after discharge was assessed by a mailed questionnaire or telephone interview. Outcome was dichotomized into good (mRS ≤ 2) and poor (mRS ≥ 3). Logistic regression analyses were calculated to determine independent predictors for good functional outcome.ResultsOverall in-hospital mortality amounted to 22.5% of all patients, and a good long-term functional outcome was achieved in 28.4%. The parameters age, length of ventilation (LOV), admission diagnosis of ICH, GBS/MG, and inoperable cerebral neoplasm as well as Therapeutic Intervention Scoring System (TISS)-28 on Day 1 were independently associated with functional outcome after one year.ConclusionsThis investigation revealed that age, LOV and TISS-28 on Day 1 were strongly predictive for the outcome. The diagnoses of hemorrhagic stroke and cerebral neoplasm leading to neurocritical care predispose for functional dependence or death, whereas patients with GBS and MG are more likely to recover after neurocritical care.

Dynamic Angiography and Perfusion Imaging Using Flat Detector CT in the Angiography Suite: A Pilot Study in Patients with Acute Middle Cerebral Artery Occlusions

BACKGROUND AND PURPOSE: Perfusion and angiographic imaging using intravenous contrast application to evaluate stroke patients is now technically feasible by flat detector CT performed by the angiographic system. The aim of this pilot study was to show the feasibility and qualitative comparability of a novel flat detector CT dynamic perfusion and angiographic imaging protocol in comparison with a multimodal stroke MR imaging protocol. MATERIALS AND METHODS: In 12 patients with acute stroke, MR imaging and the novel flat detector CT protocol were performed before endovascular treatment. Perfusion parameter maps (MTT, TTP, CBV, CBF) and MIP/volume-rendering technique images obtained by using both modalities (MR imaging and flat detector CT) were compared. RESULTS: Comparison of MIP/volume-rendering technique images demonstrated equivalent visibility of the occlusion site. Qualitative comparison of perfusion parameter maps by using ASPECTS revealed high Pearson correlation coefficients for parameters CBF, MTT, and TTP (0.95–0.98), while for CBV, the coefficient was lower (0.49). CONCLUSIONS: We have shown the feasibility of a novel dynamic flat detector CT perfusion and angiographic protocol for the diagnosis and triage of patients with acute ischemic stroke. In a qualitative comparison, the parameter maps and MIP/volume-rendering technique images compared well with MR imaging. In our opinion, this flat detector CT application may substitute for multisection CT imaging in selected patients with acute stroke so that in the future, patients with acute stroke may be directly referred to the angiography suite, thereby avoiding transportation and saving time.

Increased membrane shedding--indicated by an elevation of CD133-enriched membrane particles--into the CSF in partial epilepsy.

PURPOSE Recent analyses provided evidence that human adult cerebrospinal fluid (CSF) in addition to soluble proteins also contains membrane particles that moreover carry the somatic stem cell marker CD133. The significance of CD133 as a potential marker of cellular proliferation, including neurogenesis, remains unresolved. As adult neurogenesis has been implicated to be induced by epileptic seizures this study investigated whether patients with partial epilepsy show a varying amount of membrane-associated CD133 in CSF as compared to healthy adults. METHODS CSF samples of 34 partial epilepsy patients were analyzed and compared to 61 healthy controls. Following sequential centrifugation up to 200,000 g quantitative immunoblotting was performed using a mouse monoclonal antibody. Antigen-antibody complexes were detected using enhanced chemiluminescence, and visualized and quantified digitally. RESULTS The overall amount of membrane particle-associated CD133 was significantly increased in epilepsy patients compared to healthy controls (9.6±2.9 ng of bound CD133 antibody versus 7.4±3.8 ng; p<0.01). There were no differences according to etiology of epilepsy (cryptogenic, neoplasia, dysplasia, ammons horn sclerosis, and others). Dichotomization of the patients according to temporal versus extratemporal foci revealed a significant increase of membrane particle-associated CD133 in patients with temporal lobe epilepsy (10.88±3.3 ng of bound CD133 antibody versus 8.35±3.48 ng; p<0.05). CONCLUSION The increased amount of membrane particle-associated CD133 in the CSF of patients with partial epilepsy contributes to the ongoing debate of the source of these particles potentially emerging from subventricular zone astrocytes serving as neural stem cells. As neurogenesis in adults is related to the hippocampus, the significance of the increase of membrane particle-associated CD133 especially in temporal lobe epilepsy needs further clinical correlation.

Comparison of Conventional CTA and Volume Perfusion CTA in Evaluation of Cerebral Arterial Vasculature in Acute Stroke

BACKGROUND AND PURPOSE: CTA-like datasets can be reconstructed from whole-brain VPCTA. The aim of our study was to compare VPCTA with CTA for detection of intracranial stenosis and occlusion in stroke patients. Omitting CTA from stroke CT could reduce radiation dose. MATERIALS AND METHODS: One hundred sixty-three patients were included in this retrospective analysis. Inclusion criterion was suspected stroke within 4.5 hours after onset of symptoms. All examinations were performed on a 128-section multidetector CT scanner. Axial, coronal, and sagittal maximum intensity projections were reconstructed from CTA and from peak arterial phase of VPCTA. Images were scored for quality and presence of intracranial stenosis >50% or occlusion. For statistical analysis, the Wilcoxon signed-rank test and Fisher exact test were used, with a 2-tailed P value of .05 or less for statistical significance. RESULTS: Average image quality was superior in CTA (P < .05). However, image quality dichotomized for diagnostic significance was without difference between CTA and VPCTA (P > .05). Comparative statistical analysis revealed no significant difference for detection of intracranial stenosis and occlusion between CTA and VPCTA (P > .05). Substitution of intracranial CTA by VPCTA would lower radiation dose by 0.5 mSv. CONCLUSIONS: VPCTA is suited to assess the intracranial vasculature in patients with stroke and might have the potential to decrease radiation dose by substituting for intracranial CTA in stroke CT. Additional studies are necessary to further evaluate potential benefits of the dynamic nature of VPCTA.