Search

Background and Purpose— Several risk factors are known to increase mid- and long-term mortality of ischemic stroke patients. Information on predictors of early stroke mortality is scarce but often requested in clinical practice. We therefore aimed to develop a rapidly applicable tool for predicting early mortality at the stroke unit. Methods— We used data from the nationwide Austrian Stroke Unit Registry and multivariate regularized logistic regression analysis to identify demographic and clinical variables associated with early (≤7 days poststroke) mortality of patients admitted with ischemic stroke. These variables were then used to develop the Predicting Early Mortality of Ischemic Stroke score that was validated both by bootstrapping and temporal validation. Results— In total, 77 653 ischemic stroke patients were included in the analysis (median age: 74 years, 47% women). The mortality rate at the stroke unit was 2% and median stay of deceased patients was 3 days. Age, stroke severity measured by the National Institutes of Health Stroke Scale, prestroke functional disability (modified Rankin Scale >0), preexisting heart disease, diabetes mellitus, posterior circulation stroke syndrome, and nonlacunar stroke cause were associated with mortality and served to build the Predicting Early Mortality of Ischemic Stroke score ranging from 0 to 12 points. The area under the curve of the score was 0.879 (95% CI, 0.871–0.886) in the derivation cohort and 0.884 (95% CI, 0.863–0.905) in the validation sample. Patients with a score ≥10 had a 35% (95% CI, 28%–43%) risk to die within the first days at the stroke unit. Conclusions— We developed a simple score to estimate early mortality of ischemic stroke patients treated at a stroke unit. This score could help clinicians in short-term prognostication for management decisions and counseling.

The objective of this study was to analyse the Neurothrombectomy Network registry of the Neuromed Campus (NMC) of the Kepler University Hospital in Linz (Austria). The data were compared to the results of recently published thrombectomy trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, REVASCAT and THRACE). We retrospectively studied 246 patients with acute ischemic stroke who underwent thrombectomy between January 2012 and December 2015 at the NMC in Upper Austria. The main outcome measures were modified Rankin scale (mRS) score 0–2 at 90 days, all-cause mortality and stroke or thrombectomy-related mortality at discharge, as well as 90 days postdischarge. The median age was 70.4 years (IQR 59.9–76.9) and the median NIHSS at admission 16 (IQR 13–20). The thrombolysis in cerebral infarction (TICI) scale 2b–3 recanalization was achieved in 87.4%, 11.0% of the patients died in hospital and an additional 6.1% within 90 days after discharge. After 90 days, 56.5% had a mRS score 0–2. These data suggest that the positive results of thrombectomy reported in several randomized controlled studies can be achieved in routine clinical practice; therefore, the setting of an organized, regional stroke network proved an effective and appropriate method for delivering regional thrombectomy stroke treatment.

Summary In 2010, eight Austrian medical societies proposed a joint position statement on the management of metabolic lipid disorders for the prevention of vascular complications. An updated and extended version of these recommendations according to the current literature is presented, referring to the primary and secondary prevention of vascular complications in adults, taking into consideration the guidelines of other societies. The “Austrian Lipid Consensus – 2016 update” provides guidance for individualized risk stratification and respective therapeutic targets, and discusses the evidence for reducing vascular endpoints with available lipid-lowering therapies. Furthermore, specific management in key patient groups is outlined, including subjects presenting with coronary, cerebrovascular, and/or peripheral atherosclerosis; diabetes mellitus and/or metabolic syndrome; nephropathy; and familial hypercholesterolemia.

Background and Purpose- Several risk factors are known to increase mid- and long-term mortality of ischemic stroke patients. Information on predictors of early stroke mortality is scarce but often requested in clinical practice. We therefore aimed to develop a rapidly applicable tool for predicting early mortality at the stroke unit. Methods- We used data from the nationwide Austrian Stroke Unit Registry and multivariate regularized logistic regression analysis to identify demographic and clinical variables associated with early (≤7 days poststroke) mortality of patients admitted with ischemic stroke. These variables were then used to develop the Predicting Early Mortality of Ischemic Stroke score that was validated both by bootstrapping and temporal validation. Results- In total, 77 653 ischemic stroke patients were included in the analysis (median age: 74 years, 47% women). The mortality rate at the stroke unit was 2% and median stay of deceased patients was 3 days. Age, stroke severity measured by the National Institutes of Health Stroke Scale, prestroke functional disability (modified Rankin Scale0), preexisting heart disease, diabetes mellitus, posterior circulation stroke syndrome, and nonlacunar stroke cause were associated with mortality and served to build the Predicting Early Mortality of Ischemic Stroke score ranging from 0 to 12 points. The area under the curve of the score was 0.879 (95% CI, 0.871-0.886) in the derivation cohort and 0.884 (95% CI, 0.863-0.905) in the validation sample. Patients with a score ≥10 had a 35% (95% CI, 28%-43%) risk to die within the first days at the stroke unit. Conclusions- We developed a simple score to estimate early mortality of ischemic stroke patients treated at a stroke unit. This score could help clinicians in short-term prognostication for management decisions and counseling.

Objective A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion. Methods ENDOSTROKE is an investigator-initiated multicenter registry for patients undergoing EVT. This analysis includes 148 consecutive patients with BA occlusion, with 59% having received intravenous thrombolysis prior to EVT. Recanalization (defined as Thrombolysis in Cerebral Infarction [TICI] score 2b–3) and collateral status (using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system) were assessed by a blinded core laboratory. Good (moderate) outcome was defined as a modified Rankin Scale score of 0 to 2 (0–3) assessed after at least 3 months (median time to follow-up = 120 days). Results Thirty-four percent had good and 42% had moderate clinical outcome; mortality was 35%. TICI 2b–3 recanalization was achieved by 79%. Age, hypertension, National Institutes of Health Stroke Scale scores, collateral status, and the use of magnetic resonance imaging prior to EVT predicted clinical outcome, the latter 3 remaining independent predictors in multivariate analysis. Independent predictors of recanalization were better collateral status and the use of a stent retriever. However, recanalization did not significantly predict clinical outcome. Interpretation Beside initial stroke severity, the collateral status predicts clinical outcome and recanalization in BA occlusion. Our data suggest that the use of a stent retriever is associated with high recanalization rates, but recanalization on its own does not predict outcome. The role of other modifiable factors, including the choice of pretreatment imaging modality and time issues, warrants further investigation. Ann Neurol 2015;77:415–424

International journal of stroke 12(4), 412-415 (2017). doi:10.1177/1747493016677986, Published by Sage, London

Introduction: The endovascular treatment (EVT) of cerebral ischemia in the case of large vessel occlusion has been established over recent years. Randomized trials showed a positive impact on the clinical outcome of endovascular treatment in addition to thrombolysis with respect to clinical outcome and safety, so that this therapeutic option will be implemented in future guidelines. The role of EVT in patients treated with oral anticoagulants remains uncertain. Hypothesis: We assessed the hypothesis that application of EVT is safe with regard to the occurrence of intracranial bleeding and clinical outcome in patients taking anticoagulants. Methods: The ENDOSTROKE-Registry is a commercially independent, prospective observational study in 12 stroke centers in Germany and Austria launched in January 2011. An online tool served for data acquisition of pre-specified variables concerning endovascular stroke therapy. Results: Data from 815 patients (median age 70, 57% male) undergoing EVT and known anticoagulation status were analyzed. A total of 85 (median age 76, 52% male) patients (10.4%) took oral anticoagulants prior to EVT. Anticoagulation status as measured with INR was 2.0-3.0 in 24 patients (29%), Conclusion: The application of endovascular treatment in patients taking oral anticoagulants is safe and should be considered in acute stroke treatment as an important alternative to contraindicated intravenous thrombolysis.

GRUNDLAGEN: Die intravenose Thrombolyse (IVT) gilt in der klinischen Routine als sichere und effektive Therapie des akuten ischamischen Schlaganfalls. Unser Ziel war die Identifikation von Baseline-Pradiktoren eines exzellenten 3-Monats-Outcomes (modified Rankin Scale Score ≤1). METHODIK: Wir analysierten Daten des Osterreichischen Stroke Unit Registers (Eingaben bis 28. Februar 2007). ERGEBNISSE: Von 812 Patienten, die innerhalb 3 Stunden nach Einsetzen der Schlaganfallsymptome auf eine Stroke Unit aufgenommen und in der Folge mit IVT behandelt wurden, lag bei 386 ein 3-Monats-follow-up vor. 201 der 386 (52,1 %) Patienten hatten dabei ein exzellentes Outcome. Multivariate Regressionsanalysen identifizierten Alter (odds ratio [OR] 0,96; 95 % Konfidenzintervalle [CI] 0,94–0,98; p < 0,0005) und initialen National Institute of Health Stroke Scale (NIHSS) Score (OR 0,87; 95 % CI 0,84–0,91; p < 0,0005) als unabhangige Pradiktoren eines exzellenten 3-Monats-Outcomes. SCHLUSSFOLGERUNGEN: Alter und initialer NIHSS-Score sind starke Pradiktoren fur das Outcome nach Thrombolyse. Unsere Ergebnisse werden durch den hohen Verlust an Follow-up-Daten geschmalert.

The introduction of new direct oral anticoagulants has changed the treatment of nonvalvular atrial fibrillation. However, these changes are not yet fully reflected in current guidelines.This consensus statement, endorsed by six Austrian medical societies, provides guidance to current prophylactic approaches of thromboembolic events in nonvalvular atrial fibrillation on the basis of current evidence and published guidelines. Furthermore, some special subjects are treated, like changes in laboratory parameters and their interpretation under treatment with direct oral anticoagulants, treatment of bleedings, approach to operations, cardioversion and ablation, and specific neurological aspects. For a CHA2DS2-VASc-Score of ≥ 2, anticoagulation is recommended with a high level of evidence (1A). At the end of the consensus statement, recommendations for a number of specific patient subgroups can be found, in order to help treating physicians to arrive at appropriate therapeutic decisions.

The integrity of cerebral microvessels requires the close apposition of the endothelium to the astrocyte endfeet. Integrins α1β1 and α6β4 are cellular matrix receptors that may contribute to cerebral microvascular integrity. It has been hypothesized that focal ischemia alters integrin expression in a characteristic time-dependent manner consistent with neuron injury. The effects of middle cerebral artery occlusion (MCAO) and various periods of reperfusion on microvasclar integrin α1β1 and α6β4 expression were examined in the basal ganglia of 17 primates. Integrin subunits α1 and β1 colocalized with the endothelial cell antigen CD31 in nonischemic microvessels and with glial fibrillary acidic protein on astrocyte fibers. Rapid, simultaneous, and significant disappearance of both integrin α1 and β1 subunits and integrin α6β4 occurred by 2 hours MCAO, which was greatest in the region of neuron injury (ischemic core, Ic), and progressively less in the peripheral (Ip) and nonischemic regions (N). Transcription of subunit β1 mRNA on microvessels increased significantly in the Ic/Ip border and in multiple circular subregions within Ic. Microvascular integrin α1β1 and integrin α6β4 expression are rapidly and coordinately lost in Ic after MCAO. With loss of integrin α1β1, multiple regions of microvascular β1 mRNA up-regulation within Ic suggest that microvessel responses to focal ischemia are dynamic, and that multiple cores, not a single core, are generated. These changes imply that microvascular integrity is modified in a heterogeneous, but ordered pattern.

Background and Purpose —No neuroradiological markers have been characterized that support a timely decision for decompressive surgery in malignant middle cerebral artery (MCA) infarction (mMCAI). This case-control study was designed to analyze whether early cerebral CT (CCT) scanning provides reliable information for the prospective selection of stroke patients at risk of developing mMCAI. Methods —Thirty-one pairs (n=62) were formed with cases (mMCAI) and controls (acute but not malignant MCA infarction) closely matched in terms of age, sex, and stroke etiology. CCT was performed within 18 hours of stroke onset and analyzed by a blinded neuroradiologist according to a defined panel of 12 CCT criteria. Results —In terms of predicting mMCAI, the criteria of extended MCA territory hypodensities >67% and >50%, hemispheric brain swelling, midline shift, and hyperdense MCA sign exhibited high specificity (100%, 93.5%, 100%, 96.7%, and 83.9%, respectively) but low sensitivity (45.2%, 58.1%, 12.9%, 19.4%, and 70.9%, respectively). Two criteria yielded high sensitivity (subarachnoid space compressed, 100%; cella media compressed, 80.6%) but low specificity (29% and 74.2%, respectively). The criterion of attenuated corticomedullary contrast yielded both high specificity (96.8%) and sensitivity (87.1%). The latter remained as the crucial criterion [Exp(B)=90.8; 95% CI, 5.8 to 1427.5] in a 2-tailed logistic regression analysis with the strongest correlating parameters (Spearman correlation factor ≥0.6 or ≤−0.6). Conclusions —The analysis of CCT scans within 18 hours of stroke onset revealed an attenuated corticomedullary contrast as the crucial CCT criterion, which, with both sufficient sensitivity and specificity, predicted mMCAI with 95% certainty.

For the treatment of acute ischemic stroke (AIS), IV recominant tissue plasminogen activator (rtPA) has proven efficacy n eligible patients, but carries an increased risk of intracereral hemorrhage [1]. Preexisting anticoagulation, including the irect thrombin inhibitor dabigatran, usually contraindicates the se of rtPA. This notwithstanding, several single cases of IV tPA treatment in patients with AIS under dabigatran have een reported, with mixed results [2]. Endovascular therapy has merged as a potential, yet still experimental, alternative treatment ption for a number of clinical scenarios with contraindications o IV rtPA [3]. We report successful rescue thrombectomy in two patients who uffered AIS under treatment with dabigatran for atrial fibrillation AF).

The objective of this immunohistochemical study was to detail the distribution patterns of α and β integrin subunit expression in non-ischemic non-human primate brain in comparison to that reported for rodents and humans. For this purpose cerebral specimens were obtained from 3 adolescent male baboons by direct perfusion and immediate processing. Well-characterized monoclonal and polyclonal antibodies against human α and β integrin subunit antigens were used to define their location and distribution relative to the markers for vascular basal lamina, laminin (LM), and astrocytic fibers or glial fibrillic acid protein (GFAP). Quantitation of microvascular epitopes required computerized videoimaging microscopy and laser confocal microscopy (LCM). Each subunit was categorized into one of four microvascular patterns relative to LM antigen : (a) all microvascular diameter categories-α 1 , α 6 , and β 1 ; (b) antigen-sparing capillaries α 2 , α 4 , α 5 , α v , and β 3 ; (c) a subset of all microvascular diameter classes-α 3 , β 4 , and β 5 ; and (d) no antigen apparent, β 2 . Subunit antigens α 1 , α 2 , β 1 , and β 5 were detected on perivascular astrocytes. Subunits α 1 and β 1 , and GFAP colocalized (LCM). This quantitative survey detailed specific microvascular and astrocyte associations of certain α and β integrin subunits in non-human primate brain. Specific reproducible and consistent distributions of α and β subunits form the basis for further investigation of their responses to focal ischemia in a human relevant system.

Background: Clinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion. Methods: ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later. Results: The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization (‘futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with ‘futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile). Conclusions: This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).

Intravenous thrombolysis (IVT) for acute ischaemic stroke is safe and effective in routine clinical use. We aimed to identify baseline predictors of excellent outcome after 3 months, defined by a modified Rankin Scale scoreor=1.We analysed data entered in the Austrian Stroke Unit Registry up to February 28th 2007.Eight hundred and twelve patients received IVT after admission to a stroke unit within 3 hours of stroke onset. Of 386 patients with complete follow-up at 3 months, 201 (52.1%) had an excellent outcome. Multivariate regression analyses identified age (odds ratio (OR) 0.96; 95% confidence intervals (CI) 0.94-0.98; p0.0005) and admission score on the National Institute of Health Stroke Scale (NIHSS; OR 0.87; 95% CI 0.84-0.91; p0.0005) to be independent predictors of excellent outcome.Age and admission NIHSS score were found to powerfully predict outcome after IVT. However, results may be compromised by the loss to follow-up bias.

To test the hypothesis that pre-treatment Creactive protein (CRP) predicts outcome in stroke patients undergoing intravenous thrombolysis (IVT) treatment. We analyzed the data of 111 consecutive patients with IVT within 6 hours of stroke onset for stroke involving the middle cerebral artery territory and admission CRP ≤ 6 mg/dl. CRP levels were consistently, yet non-significantly lower in patients with unfavourable outcome definitions. Median (range) CRP levels were 0.3 (0–5.9) mg/dl vs. 0.4 (0–5.7) mg/dl (p = 0.13) in patients dependent or dead after 3 months (modified Rankin Scale score > 2; n = 59) vs. independent patients (n = 52); 0.2 (0.1–1.5) mg/dl vs. 0.4 (0–5.9) mg/dl (p = 0.28) in patients dead after 3 months (n = 14) versus survivors (n = 97); and 0.2 (0.1–0.7) mg/dl vs. 0.4 (0–5.9) mg/dl (p = 0.09) in patients with significant neurological deterioration within 24 hours (increase in ≥ 4 points on National Institute of Health Stroke scale; n = 9) vs. patients without early deterioration (n = 102). Independent predictors of dependency/death after 3 months, identified by multivariate logistic regression analyses, were baseline NIHSS score (OR = 1.31, 95 % CI 1.16–1.48, p < 0.001), time from onset to treatment (OR = 1.01, 95 % CI 1.0–1.02, p = 0.024), and presence of diabetes (OR = 8.16, 95 % CI 1.18–56.5, p = 0.033). Pre-treatment CRP clearly failed to predict outcome in stroke patients treated with IVT. Our findings contradict previously published work and highlight the need for further research on this topic.

Background and Purpose— We report the first case of 2 intravenous thrombolysis treatments within 90 hours in a patient with early recurrent stroke. Summary of Review— A 50-year-old man had improved significantly after intravenous thrombolysis for acute stroke. On the fourth day, he deteriorated dramatically because of recurrent stroke. Evidence of vessel reocclusion and profound perfusion/diffusion mismatch constituted the rationale for a second thrombolysis treatment, which resulted in vessel recanalization and significant neurologic improvement. Conclusion— The pathophysiological information obtained by multimodal magnetic resonance imaging may suit as a brain clock when repeat thrombolysis treatment is considered for early recurrent stroke.

Eine nicht-kommerzielle (akademische) Studie ist ein Forschungsprojekt, das nicht auf die Wahrung von Interessen einer kommerziell ausgerichteten Institution abzielt. Die Einstufung einer klinischen Studie als akademisch oder kommerziell ist sinnvoll bzw. vor allem fur die forschende Arzteschaft, Ethikkommissionen und Trager von Krankenanstalten wichtig, da durchaus relevante Unterschiede im Image- und Kostenbereich bestehen. Eine Unterstutzung von akademischen Studien durch kommerzielle Institutionen wie z. B. pharmazeutische Unternehmen ist unproblematisch, sofern damit nicht Auflagen verbunden sind, die eine Beeintrachtigung der objektiven Studienplanung, der Ergebnisveroffentlichung oder der Rechte des akademischen Studieninitiators an den erhobenen Daten darstellen. Relevante direkte oder indirekte Verknupfungen mit einem potentiell von den Projektergebnissen profitierenden Unternehmen der Gesundheitsbranche (z. B. grosere Beteiligungen oder finanzielle Abhangigkeiten) sprechen fur die Einstufung einer Studie als kommerziell. Ohne Offenlegung aller Unterstutzungen, Interessenkonflikte und Sondervereinbarungen ist die verlassliche Einstufung einer Studie als akademisch nicht moglich.

The concept of vascular dementia is undergoing revision. The multi-infarct model and the Alzheimer's model of dementia, usually referred to as 'multi-infarct dementia', are gradually being replaced by a much broader concept of vascular cognitive impairment. This conceptual evolution reflects a more profound understanding of the pathogenic mechanisms that underlie this complex syndrome. As a consequence of this revision new diagnostic criteria have been established during the past 25 years, resulting in new problems with regard to precise disease definition and limited inter-rater reliability. The particular criteria chosen by a clinician or investigator to diagnose vascular dementia have a major impact on epidemiology, disease management and health economic estimates.

In 15 patients (median age 33 years; range 17–74 years) suffering from acute pneumococcal (10 cases) and meningococcal (five cases) meningitis, cerebral blood flow velocity (CBFV) was measured in the M1– segment of the middle cerebral artery (MCA) by transcranial Doppler sonography, and cerebral perfusion changes were evaluated by 99m-Tchexamethylpropylene amine oxime single photon emission computed tomography (HMPAO SPECT). The objective of the study was to test whether increased CBFV during the acute phase of purulent meningitis reflects hyperemia, and to evaluate focal perfusion abnormalities and their correlation to CBFV changes. In eight patients with marked side-differences in CBFVs during the acute phase of the disease SPECT scans were normal in five. In three patients unilateral perfusion defects correlated with the side of higher CBFV. In seven patients presenting with symmetrically elevated CBFV, SPECT scans were normal in four and revealed focal abnormalities in the remaining three. Follow up SPECT scans were normal in 14/15 patients. The results of our study suggest that elevated CBFV in acute bacterial meningitis does not reflect cerebral hyperemia. Focal cerebral perfusion defects occur independently from functional alterations in the cerebral macrovasculature. A causative pathophysiologic relationship of high CBFV and focal perfusion defects cannot be drawn from these data.

Summary Background The early post-traumatic vegetative state (VS) is compatible with recovery. Various clinical and laboratory tests have failed to predict recovery so we assessed the value of cerebral magnetic-resonance imaging (MRI) in prediction of recovery. Methods 80 adult patients in post-traumatic VS had cerebral MRI between 6 weeks and 8 weeks after injury. MRIs were reviewed by three neuroradiologists for the number, sizes, and location of brain lesions. Three neurologists assessed the patients at the time of MRI and at 2 months, 3 months, 6 months, 9 months, and 12 months after injury using the Glasgow Outcome Scale. Findings At 12 months, 38 patients had recovered while 42 patients remained in the VS. The demographic characteristics and causes and severity of injury were similar in patients in persistent VS (PVS) and those who recovered (NPVS). An average of 6·1 different brain areas were injured in patients in PVS compared with 4·6 areas in patients who had NPVS. Patients in PVS revealed a significantly higher frequency of corpus callosum, corona radiata, and dorsolateral brainstem injuries than did patients who recovered. Logistic regression analysis showed that corpus callosum and dorsolateral brainstem injuries were predictive of non-recovery. The adjusted odds ratios for non-recovery of patients with a corpus callosum lesion and dorsolateral brainstem injury were 213·8 (95% Cl 14·2–3213·3), and 6·9 (1·1–42·9), respectively. In contrast, clinical characteristics, such as initial score on the Glasgow Coma Scale, age, and pupillary abnormalities failed to predict recovery. Interpretation Cerebral MRI findings in the subacute stage after head injury can predict the outcome of the post-traumatic VS. Corpus callosum and dorsolateral brainstem lesions are highly significant in predicting non-recovery.

Object. In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. Methods. Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. Conclusions. The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.

We studied the efficacy and pharmacokinetics of intraventricularly administered vancomycin in three patients with shunt-associated staphylococcal ventriculitis. We instilled 10 mg of the drug intraventricularly every 24 hours. Cerebrospinal fluid (CSF) levels were measured 1 hour after instillation and then every 2 hours. Peak vancomycin levels reached a mean of 292.9 microg/mL. The mean trough levels, measured immediately before readministration of vancomycin, were 7.6 microg/mL; this level has proved to be sufficient for maintaining the necessary steady-state serum concentration of vancomycin. All three patients were cured clinically and bacteriologically, and CSF parameters returned to normal within 5-13 days. No side effects were observed. Our results suggest that intraventricularly administered vancomycin is a valuable therapeutic strategy for treating shunt-associated staphylococcal ventriculitis. In addition, we provide evidence that 10 mg of vancomycin, administered intraventricularly every 24 hours, allows maintenance of therapeutic drug levels in the CSF for at least 24 hours.

Serial single photon emission computed tomography (SPECT), near-infrared spectroscopy (NIRS), and transcranial doppler (TCD) sonography examinations were performed to investigate changes of cerebral perfusion and tissue oxygenation in a patient with complicated cerebral malaria that have been acquired in Nigeria. On admission to the Neurologic Intensive Care Unit in Innsbruck, Austria, SPECT and NIRS revealed focal right hemispheric hypoperfusion and decreased oxygen saturation, respectively, correlating exactly to the patient's right hemispheric localizing signs. In contrast, TCD examinations of the basal cerebral vessels revealed normal flow patterns. The patient showed an initial Plasmodium falciparum parasitemia rate of 30% and was cured by intravenous quinine and oral mefloquine therapy. He was discharged without neurologic symptoms. Follow-up SPECT and NIRS examinations revealed regular cerebral perfusion and oxygenation patterns in both cortical hemispheres. In summary, the presented findings provide first evidence that noninvasive SPECT and NIRS may be important diagnostic tools in the evaluation of impaired cerebral microcirculation in patients with P. falciparum malaria.

Background and Purpose E-selectin participates in leukocyte-endothelial adhesion and the inflammatory processes that follow focal cerebral ischemia and reperfusion. The temporal and topographical patterns of microvascular E-selectin presentation after experimental focal cerebral ischemia are relevant to microvascular reactivity to ischemia. Methods The upregulation and fate of E-selectin antigen during 2 hours of middle cerebral artery occlusion (n=4) and 3 hours of occlusion with reperfusion (1 hour, n=4; 4 hours, n=6; 24 hours, n=6) were evaluated in the nonhuman primate. E-selectin and E:P-selectin immunoreactivities were semiquantitated with the use of computerized light microscopy video imaging and laser confocal microscopy. Results Three patterns of microvascular E-selectin expression, defined by the antibody E-1E4, were confirmed by complete elimination of E-1E4 binding after incubation with soluble recombinant human E-selectin: (1) Low immunoperoxidase intensity was observed in ischemic microvessels at 2 hours of occlusion extending to 4 hours of reperfusion (E-selectin/laminin=0.32±0.10). (2) A significant fraction of ischemic microvessels displayed high-intensity E-selectin signal by 24 hours of reperfusion (0.61±0.17) compared with control and nonischemic tissues (2 P P =.0005). The latter were further confirmed by an E:P-selectin immunoprobe. Conclusions E-selectin antigen is distinctively and significantly upregulated in nonhuman primate brain after focal ischemia and reperfusion. The late appearance of E-selectin in nonischemic cerebral tissues suggests stimulation by transferable factors generated during brain injury.

• In a 3-year period, 110 patients with central nervous system infections of various causes were examined serially by means of transcranial Doppler sonography. In viral-induced infections, no changes of flow velocity in basal cerebral arteries were seen, whereas in bacterial meningitis, a significant increase of blood flow velocity in the middle cerebral artery was recorded. Its extent was mainly associated with the type of the infectious agent, most frequently observed in pneumococcal meningitis (77%). The increase was up to 100% of the baseline values and was reversible in all cases. All patients were offered full-scale neurointensive care, and all subjects with bacterial meningitis were fully heparinized.

To the Editor: We read with interest the article by Montaner et al1 in which the authors claim that poststroke C-reactive protein (CRP) is a powerful prognostic tool among candidates for intravenous thrombolysis. The study raises several methodological and clinical questions. Patients with baseline CRP >6 mg/dL were excluded from the study because of probable infection before stroke. The rationale behind this arbitrary cut-point was …

We read with interest the article by Fries and Krishnan about equipoise, design bias and randomized controlled trials [1]. It is important to stress that equipoise is not the principle underlying company-driven clinical trials, which are doubtlessly necessary and useful for medical progress. As a rule, companies' clinical research departments cannot afford the risk that their hypotheses are invalid and, thus, that their trials will fail. Furthermore, equipoise in non-commercial trials is a very complex issue, which we do not intend to discuss here. So, "positive expected outcomes" seems to be an interesting and realistic alternative to equipoise. We cannot, however, agree with the authors' control group considerations. From our point of view, it is not acceptable for subjects assigned to a control group to be denied standard treatment, even if the mean expected outcome (expected outcome in the verum group plus expected outcome in the control group divided by two) is positive. One of the authors' arguments for the admissibility of control group treatments below clinical standard is that patients are autonomous and can make decisions on their own. In the case of most health problems, patients are under enormous mental pressure and are not necessarily able to weigh-up the pros and cons in an objective way. Furthermore, the feasibility of a placebo-controlled trial should not depend on a company's estimation of by how far the new treatment will exceed standard treatment. Finally, and this is the essential point, it is dangerous to undermine the patients' right to get the best possible treatment. In most European countries, social security systems enable patients to get the best possible treatment. It is hard to understand why this level of treatment should be neglected in clinical trials. In conclusion, we think that the principle of "positive expected outcomes" is an interesting and realistic approach but we should not ignore the ethical principle of "best possible treatment for every patient".

In reply Responding to Goldman's comment, we, indeed, assume that heparinization was one strategy for favorable outcome in our patients.1Both bacterial and venous cerebrovascular complications account for still high mortality rates and long-term sequelae in bacterial meningitis, in particular in pneumococcal meningitis.2,3Our data point to an obstructive process of the basal cerebral blood vessels with highest risk of developing brain ischemia throughout the first 5 days. There is strong evidence that these hemodynamic changes reflect secondary vasculitis4; additionally, following initial inflammatory damage of endothelium, the endogenous coagulation cascade might be activated, converting prothrombin into thrombin. Heparin as a thrombin antagonist should, thus, counteract possible development of local thrombosis, which—in addition to narrowing of the blood vessel—could lead to cerebral ischemia or even infarction. However, anticoagulant therapy is associated with some risk due to well-known side effects. Heparin causes transient mild thrombocytopenia in up to 25%

Summary Background Stroke is one of the leading causes of acquired epilepsy in adults. An instrument to predict whether people are at high risk of developing post-stroke seizures is not available. We aimed to develop and validate a prognostic model of late (>7 days) seizures after ischaemic stroke. Methods In this multivariable prediction model development and validation study, we developed the SeLECT score based on five clinical predictors in 1200 participants who had an ischaemic stroke in Switzerland using backward elimination of a multivariable Cox proportional hazards model. We externally validated this score in 1169 participants from three independent international cohorts in Austria, Germany, and Italy, and assessed its performance with the concordance statistic and calibration plots. Findings Data were complete for 99·2% of the predictors (99·2% for Switzerland, 100% for Austria, 97% for Germany, and 99·7% for Italy) and 100% of the outcome parameters. Overall, the risk of late seizures was 4% (95% CI 4–5) 1 year after stroke and 8% (6–9) 5 years after stroke. The final model included five variables and was named SeLECT on the basis of the first letters of the included parameters (severity of stroke, large-artery atherosclerotic aetiology, early seizures, cortical involvement, and territory of middle cerebral artery involvement). The lowest SeLECT value (0 points) was associated with a 0·7% (95% CI 0·4–1·0) risk of late seizures within 1 year after stroke (1·3% [95% CI 0·7–1·8] within 5 years), whereas the highest value (9 points) predicted a 63% (42–77) risk of late seizures within 1 year (83% [62–93] within 5 years). The model had an overall concordance statistic of 0·77 (95% CI 0·71–0·82) in the validation cohorts. Calibration plots indicated high agreement of predicted and observed outcomes. Interpretation This easily applied instrument was shown to be a good predictor of the risk of late seizures after stroke in three external validation cohorts and is freely available as a smartphone app. The SeLECT score has the potential to identify individuals at high risk of seizures and is a step towards more personalised medicine. It can inform the selection of an enriched population for antiepileptogenic treatment trials and will guide the recruitment for biomarker studies of epileptogenesis. Funding None.