Pulse pressure variability is associated with unfavorable outcomes in acute ischaemic stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. METHODS: Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models. RESULTS: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90-day mortality (P < 0.001). Every 5-mmHg increase in the 24-h PP variability was independently associated with a 36% decrease in the likelihood of 90-day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52-0.80) and a 60% increase in the odds of 90-day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23-2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. CONCLUSIONS: Increased PP variability appears to be independently associated with adverse short-term and long-term functional outcomes of AIS patients treated with IVT.

Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH. METHODS: We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following symptom onset. RESULTS: Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58] with no heterogeneity (I2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I2 = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001]. CONCLUSIONS: Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH.

Differential leukocyte counts on admission predict outcomes in patients with acute ischaemic stroke treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: To determine the association of differential leukocyte counts on admission with efficacy and safety outcomes in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS: Consecutive patients with AIS receiving IVT were evaluated at two stroke centers. Differential leukocyte counts and neutrophil:lymphocyte ratio (NLR) were determined during the initial 12 h of admission. Efficacy outcomes were favorable functional outcome (FFO) (modified Rankin Scale scores of 0-1) and functional independence (FI) (modified Rankin Scale scores of 0-2) at 3 months, whereas safety outcomes were symptomatic intracranial hemorrhage and 3-month mortality. RESULTS: Among 657 IVT-treated patients with AIS, the mean age was 64 ± 14 years, 50% were female and median National Institutes of Health Stroke Scale score was 7 points (interquartile range, 4-13). Lower neutrophil and leukocyte counts and NLR counts were observed in patients with 3-month FFO and FI, whereas higher counts were observed in patients who died at 3 months. The best discriminative factors for 3-month FFO and FI were NLR < 2.2 (sensitivity 51.4%, specificity 63.1%) and leukocyte count <8100/µL (sensitivity 57.5%, specificity 55.1%), respectively. After adjustment for potential confounders, NLR < 2.2 was associated with higher odds of FFO [odds ratio (OR), 1.56; 95% confidence interval (CI), 1.08-2.24; P = 0.018], whereas leukocyte count <8100/µL demonstrated higher odds of 3-month FI (OR, 1.69; 95% CI, 1.11-2.57; P = 0.014) and lower odds of 3-month mortality (OR, 0.31; 95% CI, 0.16-0.60; P = 0.001). Combined neutrophil (<6800/µL) and leukocyte (<8100/µL) counts demonstrated a strong interaction for 3-month FI (OR, 1.73; 95% CI, 1.13-2.67; P interaction = 0.012). CONCLUSIONS: Differential leukocyte counts on admission were independently associated with clinical outcomes in patients with AIS treated with IVT. These inflammatory biomarkers are potential targets for adjunctive neuroprotection in this stroke subgroup.

Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. METHODS: Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. RESULTS: A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. CONCLUSIONS: High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.

[Biomechanical Analysis of Posture and Movement Coordination in Standing Human During Trunk Bending in the Sagittal Plane].

In most motor acts to achieve a behavioral goal requires coordination of posture and movement. In this paper, such coordination is studied by the example of human trunk bending in. the sagittal plane. Such movements are difficult to study because both components of this motor act (main - bending per se, and "accessory" - posture aimed on equilibrium. maintenance) involve massive movements of body segments, which complicates separation of these components. Their separation is based on the modem ideas about the special features of the posture component as compared with the main component. It is shown that the main and posture components correspond to the move- ments along eigenvectors of the dynamic equation. These movements are unique because they demonstrate at the same time "kinematic" as well as "dynamic" synergies. They were called there- fore "natural synergies". The coordination of natural synergies is investigated in human during standing on the wide and narrow supports. It is shown that the experimentally observed coordination is close to optimal, providing minimum movement of the center of pressure. This ensures the center of pressure Position keeping inside the support area that is necessary for equilibrium maintenance.

[Mitochondrial DNA Polymorphism in Different Populations of Spangled Orloff Chickens].

For the first time, the genetic diversity of the Spangled Orloff chickens was studied by analyzing the polymorphism of the hypervariable region in the D-loop of mitochondrial DNA (mtDNA). Samples for the analysis were collected at the farms ofthe All-Russia Poultry Research and Technological Institute (VNITIP), the All-Russia Institute of Farm Animal Genetics and Breeding (VNIIGRZh), and the Moscow Zoo. The D-loop partial sequences (between nucleotide positions 57 and 523) were determined according to the reference sequence of Gallus gallus spadiceus mtDNA, NC_007235 in 39 individuals obtained from these populations (GenBank Accession Nos. KM391754-KM391792). In the analyzed mtDNA fragment, a total of 20 polymorphic sites localized between positions 167 and 368, as well as at position 446, were described in Spangled Orloff chickens. One polymorphic site at position 221 (haplogroup E, haplotype ORL-2) was unique. All of the identified nucleotide changes were transition-type substitutions. Overall, based on the analysis of poly- morphic sites in the hypervariable fragment of the D-loop of Spangled Orloff chicken mtDNA, we found seven haplotypes belonging to four haplogroups (A, B, C, and E). Haplogroup E (haplotypes ORL-1, ORL-2, and ORL-3) was present in the majority of the studied individual, with the frequencies of 0.77 in the total sample and 0.47 in the VNIIGRZh farm population. Haplogroups A (haplotypes ORL-4 and ORL-7), B (ORL-6), and C (ORL-5) were found only in samples from the VNIIGRZh farm. The studied mtDNA region revealed a lower level of polymorphism in the VNITIP and Moscow Zoo populations, which only had the ORL-1 and ORL-3 haplotypes belonging to Haplogroup E, respectively. Our data suggested that the studied Spangled Orloff chicken populations differed in the composition and frequencies of mtDNA haplogroups and haplotypes.

Closed-loop and open-loop control of posture and movement during human trunk bending.

Closed-loop (CL) and open-loop (OL) types of motor control during human forward upper trunk bending are investigated. A two-joint (hip and ankle) biomechanical model of the human body is used. The analysis is performed in terms of the movements along eigenvectors of the motion equation ("eigenmovements" or "natural synergies"). Two analyzed natural synergies are called "H-synergy" (Hip) and "A-synergy" (Ankle) according to the dominant joint in each of these synergies. Parameters of CL control were estimated using a sudden support platform displacement applied during the movement execution. The CL gain in the H-synergy increased and in the A-synergy decreased during the movement as compared with the quiet standing. The analysis of the time course of OL control signal suggests that the H-synergy (responsible for the prime movement, i.e. bending per se) is controlled according to the EP theory whereas for the associated A-synergy (responsible for posture adjustment, i.e. equilibrium maintenance) muscle forces and gravity forces are balanced for any its final amplitude and therefore the EP theory is not applicable to its control.

Emulsive polymerization as a method of enzyme modification preserving biological properties of nanostructures.

The proposed method of emulsive polymerization provides the possibility of modifying and obtaining insoluble forms of superoxide dismutase (SOD), glutathione reductase, and streptolysin-O preserving nanoobjects (conformationally active centers and antigenic determinants) in their native states. Apart from enzymatic and immunological properties, the samples acquired some new features: resistance to high temperature, resistance to 3 M KCNS solution and buffer solutions with high concentration of hydrogen ions, and resistance to preserving solutions. Magnetic properties provide the possibility of simplifying enzyme-linked immunosorbent and immunofluorescence assays. In addition, sensitivity of these assays was by an order of magnitude higher and the specificity fully preserved. Taking all the facts into account, we prepared agents for long-term and repeated use. Due to preserved enzymatic properties, insoluble forms of SOD and glutathione reductase can be considered as a tool for correction of peroxide-antioxidant balance and associated immunological abnormalities.

Current and future recanalization strategies for acute ischemic stroke.

In a quest for stroke treatment, reperfusion proved to be the first key to the puzzle. Systemic tissue plasminogen activator (tPA), the first and currently the only approved treatment, is also the fastest way to initiate thrombolyis for acute ischemic stroke. tPA works by induction of mostly partial recanalization since stroke patients often have large thrombus burden. Thus, early augmentation of fibrinolysis and multi-modal approach to improve recanalization are desirable. This review focuses on the following strategies available to clinicians now or being tested in clinical trials: (a) faster initiation of tPA infusion; (b) sonothrombolysis; (c) intra-arterial revascularization, bridging intravenous and intra-arterial thrombolysis, mechanical thrombectomy and aspiration; and (d) novel experimental approaches. Despite these technological advances, no single strategy was yet proven to be a 'silver bullet' solution to reverse acute ischemic stroke. Better outcomes are expected with faster treatment leading to early, at times just partial flow improvement rather than achieving complete recanalization with lengthy procedures. Arterial re-occlusion can occur with any of these approaches, and it remains a challenge since it leads to poor outcomes and no clinical trial data are available yet to determine safe strategies to prevent or reverse re-occlusion.

Effect of body positioning during transcranial Doppler detection of right-to-left shunts.

We adopted an expanded transcranial Doppler (TCD) protocol to evaluate if additional injections of agitated saline in different positions would improve shunt detection or grading. We report the safety and feasibility of this expanded contrast TCD protocol. Patients with ischemic stroke were evaluated. The standard protocol for RLS detection was followed and expanded after the initial injection in the supine position to the right lateral decubitus, upright sitting, and sitting with right lateral leaning. Changes in blood pressure, heart rate, and any subjective complaints were noted. Changes in body position and additional agitated saline injections were tolerated. Right-to-left shunt (RLS) was detected in 35% of patients (n = 55). If the initial supine testing was negative, all subsequent positions/injections were also negative for RLS. However, if the supine injection was positive for RLS, the change in body positions increased the microbubble (microB) count in eight of 19 (42%) RLS-positive patients. The mean microB count in RLS-positive patients was 20 (95% CI: 9-32). The use of three additional body positions increased the microB count to 73 (95% CI: 13-132). The highest microB yield was achieved in the upright sitting position. Our findings support the safety and feasibility of the expanded TCD protocol. If the initial supine Valsalva-aided contrast TCD test is negative, there may be no need to study the patient in additional positions. However, if microB are detected in the supine position, additional testing for RLS in alternative positions may be found to be worthwhile.

Thrombotic occlusion of the common carotid artery (CCA) in acute ischemic stroke treated with intravenous tissue plasminogen activator (TPA).

Although common carotid artery (CCA) occlusions are rare, acute clinical presentations vary from mild to devastating strokes primarily due to tandem occlusions in the intracranial arteries. Three patients with acute CCA occlusions were treated with systemic tissue plasminogen activator (TPA). Blood pressures were kept at the upper limits allowed with TPA therapy with fluid balance and the 'head-down' position. Recanalization occurred in intracranial vessels only. Marked early neurological improvement occurred in two of three patients. CCA occlusions should not be considered contra-indication to systemic thrombolysis.

Diagnostic Accuracy of Transcranial Doppler for Brain Death Confirmation: Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Transcranial Doppler is a useful ancillary test for brain death confirmation because it is safe, noninvasive, and done at the bedside. Transcranial Doppler confirms brain death by evaluating cerebral circulatory arrest. Case series studies have generally reported good correlations between transcranial Doppler confirmation of cerebral circulatory arrest and clinical confirmation of brain death. The purpose of this study is to evaluate the utility of transcranial Doppler as an ancillary test in brain death confirmation. MATERIALS AND METHODS: We conducted a systematic review of the literature and a diagnostic test accuracy meta-analysis to compare the sensitivity and specificity of transcranial Doppler confirmation of cerebral circulatory arrest, by using clinical confirmation of brain death as the criterion standard. RESULTS: We identified 22 eligible studies (1671 patients total), dating from 1987 to 2014. Pooled sensitivity and specificity estimates from 12 study protocols that reported data for the calculation of both values were 0.90 (95% CI, 0.87-0.92) and 0.98 (95% CI, 0.96-0.99), respectively. Between-study differences in the diagnostic performance of transcranial Doppler were found for both sensitivity (I(2) = 76%; P < .001) and specificity (I(2) = 74.3%; P < .001). The threshold effect was not significant (Spearman r = -0.173; P = .612). The area under the curve with the corresponding standard error (SE) was 0.964 ± 0.018, while index Q test ± SE was estimated at 0.910 ± 0.028. CONCLUSIONS: The results of this meta-analysis suggest that transcranial Doppler is a highly accurate ancillary test for brain death confirmation. However, transcranial Doppler evaluates cerebral circulatory arrest rather than brain stem function, and this limitation needs to be taken into account when interpreting the results of this meta-analysis.

Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement.

BACKGROUND: Arterial recanalization precedes clinical improvement or may lead to hemorrhage or reperfusion injury. Speed of clot lysis was not previously measured in human stroke. METHODS AND RESULTS: Transcranial Doppler (TCD) and the National Institutes of Health Stroke Scale (NIHSS) were used to monitor consecutive patients receiving intravenous tissue plasminogen activator (tPA), before tPA bolus and at 24 hours. Patients with complete or partial recanalization of the middle cerebral or basilar artery on TCD were studied. Recanalization was classified a priori as sudden (abrupt appearance of a normal or stenotic low-resistance signal), stepwise (flow improvement over 1 to 29 minutes), or slow (>/=30 minutes). Recanalization was documented in 43 tPA-treated patients (age 68+/-17 years; NIHSS score 16.8+/-6, median 15 points). tPA bolus was given at a mean of 135+/-61 minutes after symptom onset. Recanalization began at a median of 17 minutes and was completed at 35 minutes after tPA bolus, with mean duration of recanalization of 23+/-16 minutes. Recanalization was sudden in 5, stepwise in 23, and slow in 15 patients. Faster recanalization predicted better short-term improvement (P=0.03). At 24 hours, 80%, 30%, and 13% of patients in these respective recanalization groups had NIHSS scores of 0 to 3. Symptomatic hemorrhage occurred in only 1 patient, who had stepwise recanalization 5.5 hours after stroke onset. Slow or partial recanalization with dampened flow signal was found in 53% of patients with total NIHSS scores >10 points at 24 hours (P=0.01). Complete recanalization (n=25) occurred faster (median 10 minutes) than partial recanalization (n=18; median 30 minutes; P=0.0001). CONCLUSIONS: Rapid arterial recanalization is associated with better short-term improvement, mostly likely because of faster and more complete clot breakup with low resistance of the distal circulatory bed. Slow (>/=30 minutes) flow improvement and dampened flow signal are less favorable prognostic signs. These findings may be evaluated to assist with selection of patients for additional pharmacological or interventional treatment.

Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator.

BACKGROUND AND PURPOSE: TIMI angiographic classification measures coronary residual flow and recanalization. We developed a Thrombolysis in Brain Ischemia (TIBI) classification by using transcranial Doppler (TCD) to noninvasively monitor intracranial vessel residual flow signals. We examined whether the emergent TCD TIBI classification correlated with stroke severity and outcome in patients treated with intravenously administered tPA (IV-tPA). METHODS: TCD examination occurred acutely and on day 2. TIBI flows were determined at distal MCA and basilar artery depths, depending on occlusion site. TIBI waveforms were graded as follows: 0, absent; 1, minimal; 2, blunted; 3, dampened; 4, stenotic; and 5, normal. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours after administration of tPA. RESULTS: One hundred nine IV tPA patients were studied. Mean+/-SD age was 68+/-16 years; median NIHSS score before administration of tPA (pre-tPA) was 17.5. The tPA bolus was administered 143+/-58 minutes and the TCD examination 141+/-57 minutes after symptom onset. Pre-tPA NIHSS scores were higher in patients with TIBI grade 0 than TIBI grade 4 or 5 flow. TIBI flow improvement to grade 4 or 5 occurred in 35% of patients (19/54) with an initial grade of 0 or 1 and in 52% (12/23) with initial grade 2 or 3. The 24-hour NIHSS scores were higher in follow-up in patients with TIBI grade 0 or 1 than those with TIBI grade 4 or 5 flow. TIBI flow recovery correlated with NIHSS score improvement. Lack of flow recovery predicted worsening or no improvement. In-hospital mortality was 71% (5/7) for patients with posterior circulation occlusions; it was 22% (11/51) for patients with pre-tPA TIBI 0 or 1 compared with 5% (1/19) for those with pre-tPA TIBI 2 or 3 anterior circulation occlusions. CONCLUSIONS: Emergent TCD TIBI classification correlates with initial stroke severity, clinical recovery, and mortality in IV-tPA-treated stroke patients. A flow-grade improvement correlated with clinical improvement.

Seizures after stroke: a prospective multicenter study.

BACKGROUND: Studies of seizures after stroke have largely been retrospective, with small patient numbers and limited statistical analysis. Much of the doctrine about seizures after stroke is not evidenced based. OBJECTIVE: To determine the incidence, outcome, and risk factors for seizures after stroke. DESIGN: International, multicenter, prospective, analytic inception cohort study conducted for 34 months. PATIENTS AND SETTING: There were 2021 consecutive patients with acute stroke admitted to university teaching hospitals with established stroke units. After exclusion of 124 patients with previous epilepsy or without computed tomographic diagnosis, 1897 were available for analysis. Mean follow-up was 9 months. MAIN OUTCOME MEASURES: Occurrence of 1 or more seizures after stroke, stroke disability, and death after stroke. RESULTS: Seizures occurred in 168 (8.9%) of 1897 patients with stroke (28 [10.6%] of 265 with hemorrhagic and 140 [8.6%] of 1632 with ischemic stroke). On Kaplan-Meier survival analysis, patients with hemorrhagic stroke were at significantly greater risk of seizures (P =.002), with an almost 2-fold increase in risk of seizure after stroke (hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.26-2.73; P =.002). On multivariate analysis, risk factors for seizures after ischemic stroke were cortical location of infarction (HR, 2.09; 95% CI, 1. 19-3.68; P<.01) and stroke disability (HR, 2.10; 95% CI, 1.16-3.82; P<.02). The only risk factor for seizures after hemorrhagic stroke was cortical location (HR, 3.16; 95% CI, 1.35-7.40; P<.008). Recurrent seizures (epilepsy) occurred in 47 (2.5%) of 1897 patients. Late onset of the first seizure was an independent risk factor for epilepsy after ischemic stroke (HR, 12.37; 95% CI, 4.74-32.32; P<. 001) but not after hemorrhagic stroke. CONCLUSIONS: Seizures occur more commonly with hemorrhagic stroke than with ischemic stroke. Only a small minority later develop epilepsy. Patients with a disabling cortical infarct or a cortical hemorrhage are more likely to have seizures after stroke; those with late-onset seizures are at greater risk of epilepsy.

Intravenous tissue-type plasminogen activator therapy for ischemic stroke: Houston experience 1996 to 2000.

CONTEXT: Intravenous tissue-type plasminogen activator (tPA) therapy using the National Institute of Neurological Disorders and Stroke criteria has been given with variable safety to less than 5% of the patients who have ischemic strokes nationwide. Our center is experienced in treating large numbers of stroke patients with intravenous tPA. OBJECTIVE: To report our total 4-year experience in the treatment of consecutive patients who had an ischemic stroke. DESIGN: Prospective inception cohort registry of all patients seen by our stroke team and an additional retrospective medical record review of all patients treated between January 1, 1996, and June 1, 2000. SETTING: A veteran stroke team composed of fellows and stroke-specialty faculty servicing 1 university and 3 community hospitals in a large urban setting. PATIENTS: Consecutive patients with ischemic stroke treated within the first 3 hours of symptom onset. INTERVENTION: According to the National Institute of Neurological Disorders and Stroke protocol, 0.9 mg/kg of intravenous tissue-type plasminogen activator was administered. MAIN OUTCOME MEASURES: Number and proportion treated, patient demographics, time to treatment, hemorrhage rates, and clinical outcome. RESULTS: A total of 269 patients were treated between January 1, 1996, and June 1, 2000. Their mean age was 68 years (age range, 24-93 years); 48% were women. This represented 9% of all patients admitted with symptoms of cerebral ischemia at our most active hospital (over the final 6 months, 13% of all patients with symptoms of cerebral ischemia and 15% of all acute ischemic stroke patients). Before treatment the mean +/- SD National Institutes of Health Stroke Scale (NIHSS) score was 14.4 +/- 6.1 points (median, 14 points; range, 4-33 points). A tPA bolus was given at 137 minutes (range, 30-180 minutes); 28% of the patients were treated within 2 hours. The mean door-to-needle time was 70 minutes (range, 10-129 minutes). The symptomatic intracerebral hemorrhage rate was 5.6% of those patients with a second set of brain scans (4.5% of all patients), with a declining trend from 1996 to 2000. Protocol violations were found in 13% of all patients; the symptomatic intracerebral hemorrhage rate in these patients was 15%. At 24 hours, the NIHSS score was 10 +/- 8 points (median, 8 points; range, 0-36 points). In-hospital mortality was 15% and the patients' discharge NIHSS scores were 7 +/- 7 points (median, 3 points; range, 0-35 points). CONCLUSIONS: Intravenous tPA therapy can be given to up to 15% of the patients with acute ischemic stroke with a low risk of symptomatic intracerebral hemorrhage. Successful experience with intravenous tPA therapy depends on the experience and organization of the treating team and adherence to published guidelines.

Do-not-resuscitate orders in acute stroke.

Although the general guidelines for do-not-resuscitate (DNR) orders apply to acute stroke patients, few data are available to aid decision-making. With a view to developing specific guidelines for use in patients with acute stroke, we decided to evaluate the clinical factors associated with DNR orders at our university teaching hospital. We prospectively studied 450 consecutive patients with acute hemispheric strokes (237 men and 213 women, mean age 75 +/- 12 years). Thirty-six patients (8%) had intracerebral hemorrhage (ICH) and 414 (92%) had ischemic strokes. Overall inhospital mortality was 26%. DNR status was given to 31% of all patients at some time during their admission (83% of those died). DNR decision-making was closely associated with the severity of the neurologic deficit (Canadian Neurological Scale score < or = 5); the patient's incapacity for informed DNR decision-making; age (> 60 years); and devastating ICH unsuitable for surgery (p < 0.001). Fifty-three percent of DNR orders were given on admission (first 24 hours of the hospital stay), 35% during the first week of the hospital stay, due to brain damage, and 12% at any time between days 8 and 44 due to systemic complications. Once DNR status was given, 53% of patients continued to receive normal nutrition and 60% still received medical or surgical treatment. Although the current practice of DNR orders in patients with acute stroke is generally satisfactory, some criteria (eg, age and operable ICH) need revision.(ABSTRACT TRUNCATED AT 250 WORDS)

Mass effect and death from severe acute stroke.

BACKGROUND: In severe acute stroke, the degree of midline cerebral displacement is related to level of consciousness but not to survival. Early identification of patients at high risk of death from mass effect would assist patient management decisions. METHODS: We measured lesion volume, horizontal pineal displacement (PD), and horizontal septum pellucidum displacement (SD) on axial CT of consecutive patients with severe (Canadian Neurological Scale score < or = 5) acute hemispheric stroke. We correlated CT measurements with the probability of 14-day survival. RESULTS: Forty-six (39%) of 118 patients died within 14 days and 72 (61%) died within 1 year following stroke. Crude risk factors for 14-day mortality were as follows: lesion volume > or = 400 ml, SD > or = 9 mm, PD > or = 4 mm, intraventricular hemorrhage, and coma on admission. Only SD (p = 0.001) and coma on admission (p = 0.019) remained significant in multivariate analysis, but PD was highly correlated with SD (r = 0.82). PD of > or = 4 mm on a scan performed within 48 hours of stroke onset identified patients with a low probability of 14-day survival (0.16; CI 0 to 0.32) with a specificity of 89% and a sensitivity of 46%. CONCLUSIONS: The degree of horizontal midline cerebral displacement correlates with the likelihood of death following stroke. Patients with > or = 4 mm PD on CT performed within 48 hours of stroke onset are at high risk for early death.