Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke.

BACKGROUND: Early decompressive hemicraniectomy reduces mortality without increasing the risk of very severe disability among patients 60 years of age or younger with complete or subtotal space-occupying middle-cerebral-artery infarction. Its benefit in older patients is uncertain. METHODS: We randomly assigned 112 patients 61 years of age or older (median, 70 years; range, 61 to 82) with malignant middle-cerebral-artery infarction to either conservative treatment in the intensive care unit (the control group) or hemicraniectomy (the hemicraniectomy group); assignments were made within 48 hours after the onset of symptoms. The primary end point was survival without severe disability (defined by a score of 0 to 4 on the modified Rankin scale, which ranges from 0 [no symptoms] to 6 [death]) 6 months after randomization. RESULTS: Hemicraniectomy improved the primary outcome; the proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, as compared with 18% in the control group (odds ratio, 2.91; 95% confidence interval, 1.06 to 7.49; P=0.04). This difference resulted from lower mortality in the surgery group (33% vs. 70%). No patients had a modified Rankin scale score of 0 to 2 (survival with no disability or slight disability); 7% of patients in the surgery group and 3% of patients in the control group had a score of 3 (moderate disability); 32% and 15%, respectively, had a score of 4 (moderately severe disability [requirement for assistance with most bodily needs]); and 28% and 13%, respectively, had a score of 5 (severe disability). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group. CONCLUSIONS: Hemicraniectomy increased survival without severe disability among patients 61 years of age or older with a malignant middle-cerebral-artery infarction. The majority of survivors required assistance with most bodily needs. (Funded by the Deutsche Forschungsgemeinschaft; DESTINY II Current Controlled Trials number, ISRCTN21702227.).

Clinical Presentation and Multi-Parametric Screening Surrogates of Ischemic Stroke Patients Suffering from Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) represents a life-threatening condition due to complications like cardiac failure and thromboembolism. In ischemic stroke, IE formally excludes patients from approaches addressing the recanalization of occluded vessels, challenging decision-making in the early phase of hospitalization. This study aimed at the rate and clinical course of stroke patients with IE and explored clinical, imaging-based and serum parameters, which would allow early identification. METHODS: A hospital-based registry containing 1,531 ischemic stroke patients was screened for IE identified by echocardiography. In addition to clinical parameters, patterns of cerebral manifestation as well as a variety of inflammatory serum and myocardial markers were analyzed concerning their predictive impact for identifying affected patients. RESULTS: IE was found in 26 patients (1.7%) and was associated with an increased body temperature and cardiac murmurs. Patients suffering from IE demonstrated a more severe clinical affection at hospital discharge and an impaired symptom decline during hospitalization, further deteriorated by the use of systemic thrombolysis. Distribution of cerebral infarction patterns did not differ between the groups. C-reactive protein (CRP) and leukocyte count as well as troponin and myoglobin, taken at hospital admission, were found to be significantly associated with IE. CONCLUSIONS: IE in stroke patients is associated with worse clinical outcome, complicated by intravenously applied thrombolysis, and therefore needs to be screened during the early phase of hospitalization. Increased serum levels of CRP and leukocyte count in combination with an increased body temperature or abnormal cardiac murmurs should entail rapid initiation of further diagnostics, that is, transoesophageal echocardiography.

Distance to Thrombus in Acute Middle Cerebral Artery Occlusion Predicts Target Mismatch and Ischemic Penumbra.

BACKGROUND AND PURPOSE: In patients with occlusion of the middle cerebral artery (MCA) treated by intravenous thrombolysis (IVT), the distance to thrombus (DT) has been proposed as a predictor of outcome. The purpose of the present study was to investigate how DT relates to dynamic susceptibility contrast perfusion metrics. METHODS: Retrospective analysis was undertaken of patients who were diagnosed with acute MCA occlusion by magnetic resonance imaging and treated with IVT. Volumes of time-to-maximum (Tmax) perfusion deficits and diffusion-weighted imaging (DWI) lesions, diffusion-perfusion mismatch volumes, and the presence of target mismatch were determined. Correlations between the above stoke measures and DT were then calculated. RESULTS: Fifty-five patients were included. DT showed significant inverse correlations with Tmax greater than 4, 6, 8, and 10 seconds, respectively, and mismatch volumes. Using the DT group median (14 mm) as a separator, significant intergroup differences were observed for Tmax greater than 4, 6, and 8 seconds, respectively, and for mismatch volumes. Grouping DT into quartiles showed significant intergroup differences regarding mismatch volumes and Tmax values greater than 4 and 6 seconds. Binary logistic regression identified DT (odds ratio [OR] = .89; 95% confidence interval [CI], .81-.99) and DWI lesion volumes (OR = .92; 95% CI, .86-.97) as independent predictors of target mismatch. A low DT predicted target mismatch with an area under the curve of .69. CONCLUSIONS: DT correlates inversely with Tmax perfusion deficits and mismatch volumes and acts as an independent predictor of target mismatch.

Distance to thrombus in acute middle cerebral artery occlusion: a predictor of outcome after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: In patients with acute middle cerebral artery (MCA) stroke, therapeutic decisions are influenced by the location of the occlusion. This study aimed to analyze clinical outcomes in patients with acute ischemic MCA stroke treated with systemic intravenous thrombolysis (IVT) using recombinant tissue plasminogen activator, according to the location of the occlusion. METHODS: Of 621 patients screened, 136 with acute stroke and MCA occlusion confirmed by CT angiography were retrospectively included in this study. The distance from the carotid T to the thrombus (DT) on coronal maximum intensity projection images and the thrombus length were measured. The correlation between DT and the modified Rankin Scale score at 90 days was analyzed. RESULTS: DT was an independent predictor of clinical outcome in stroke patients treated with IVT. A long DT was significantly correlated with a good clinical outcome (modified Rankin Scale score at 90 days ≤2). A poor clinical outcome was exponentially more likely than a good outcome when the DT was <16 mm (P<0.001). The thrombus length was not correlated with the modified Rankin Scale score at 90 days. A long thrombus (>8 mm) occurred significantly more often in the proximal MCA than the distal MCA (P<0.001). CONCLUSION: DT is an independent predictor of clinical outcome in patients with acute MCA occlusion treated with IVT. In acute stroke with MCA occlusion confirmed by CT angiography and DT <16 mm, the likelihood of a good clinical outcome after treatment with IVT was exponentially <50%. This might warrant the evaluation of other therapy forms than IVT in patients with proximal MCA occlusion.

Distance to thrombus on MR angiography predicts outcome of middle cerebral artery occlusion treated with IV thrombolysis.

INTRODUCTION: The distance to thrombus (DT) on CT angiography was recently proposed as a predictor of outcome in patients treated by intravenous thrombolysis (IVT) for stroke due to occlusion of the middle cerebral artery (MCA). The purpose of the present study was to validate its inter-rater reliability and its prognostic value on contrast-enhanced magnetic resonance angiography (CE-MRA). Furthermore, we investigated the relation between DT and FLAIR-vascular hyperintensities (FVH) as a surrogate of collateral circulation and hypoperfusion. METHODS: Patients with acute MCA occlusions treated by IVT and diagnosed with magnetic resonance imaging (MRI) were included. Two readers measured DT. FVH and acute DWI lesion volumes were quantified. Clinical status was determined using the initial NIH stroke scale (NIHSS) and 90-day modified Rankin Scale (90d mRS). RESULTS: Sixty-one patients showed a lesion on diffusion-weighted magnetic resonance images and an occlusion of the MCA on CE-MRA. We found significant inverse correlations between DT and NIHSS scores at admission (ρ = -0.29; P = 0.02), DT and mRS at 90 days (ρ = -0.29; P = 0.04), and between DT and FVH (ρ = -0.32; P = 0.01). For a DT <22 mm, the likelihood of an unfavorable outcome (90d mRS 3-6 or NIHSS score improvement of ≤10 points at discharge) was >50 %. Initial DWI lesion volumes showed no correlation with the outcome. Excellent inter-rater agreement for DT was observed (Cronbach's α = 0.98; P < 0.001). CONCLUSIONS: DT on CE-MRA is reliably measurable, correlates inversely with FLAIR-vascular hyperintensities, and predicts outcome in patients with acute MCA occlusion treated with IVT.

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.

Remote or extraischemic intracerebral hemorrhage--an uncommon complication of stroke thrombolysis: results from the safe implementation of treatments in stroke-international stroke thrombolysis register.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage after treatment with intravenous recombinant tissue-type plasminogen activator for ischemic stroke can occur in local relation to the infarct, as well as in brain areas remote from infarcted tissue. We aimed to describe risk factors, 3-month mortality, and functional outcome in patients with the poorly understood complication of remote intracerebral hemorrhage, as well as local intracerebral hemorrhage. METHODS: In this study, 43 494 patients treated with intravenous recombinant tissue-type plasminogen activator, with complete imaging data, were enrolled in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) during 2002 to 2011. Baseline data were compared among 970 patients (2.2%) with remote parenchymal hemorrhage (PHr), 2325 (5.3%) with PH, 438 (1.0%) with both PH and PHr, and 39 761 (91.4%) without PH or PHr. Independent risk factors for all hemorrhage types were obtained by multivariate logistic regression. RESULTS: Previous stroke (P=0.023) and higher age (P<0.001) were independently associated with PHr, but not with PH. Atrial fibrillation, computed tomographic hyperdense cerebral artery sign, and elevated blood glucose were associated with PH, but not with PHr. Female sex had a stronger association with PHr than with PH. Functional independence at 3 months was more common in PHr than in PH (34% versus 24%; P<0.001), whereas 3-month mortality was lower (34% versus 39%; P<0.001). CONCLUSIONS: Differences between risk factor profiles indicate an influence of previous vascular pathology in PHr and acute large-vessel occlusion in PH. Additional research is needed on the effect of pre-existing cerebrovascular disease on complications of recanalization therapy in acute ischemic stroke.

Mechanical thrombectomy in patients with acute vertebrobasilar occlusion using the Trevo device: a single-centre experience.

INTRODUCTION: The purpose of this study is to investigate the efficacy and safety of mechanical thrombectomy in patients with acute vertebrobasilar artery occlusion (VBAO) using the Trevo Stentriever™ device. METHODS: Twenty patients diagnosed with VBAO underwent digital subtraction angiography (DSA) with the intention to perform mechanical thrombectomy with stent-retrievers between August 2011 and October 2013. Two patients were excluded because another device was primarily used; in two other patients, thrombectomy was not possible. RESULTS: Thrombectomy with the Trevo device was performed in 16 patients. The Stentriever™ was used either as the sole device (56.3 %) or in conjunction with up to four additional devices or techniques. Thirty-three clot retrieval manoeuvres were performed (mean 2.1 ± 1.3, range 1-5); the device could be deployed and retrieved in all manoeuvres (100 %). No device-related complications occurred. Mean duration of the endovascular intervention was 71.8 min (±39.9; range 22-144). Complete or near complete recanalization (thrombolysis in cerebral infarction (TICI) ≥2b) was achieved in 13 patients (81.3 %). Eleven patients (68.8 %) survived and seven patients (43.8 %) showed a good clinical outcome at discharge, defined as modified Rankin Scale (mRS) 0-2 or National Institute of Health Stroke Scale (NIHSS) improvement ≥10 points. Including the two patients in whom thrombectomy was not possible, successful recanalization, good clinical outcome and survival were achieved in 72.2, 38.9 and 61.1 %, respectively. CONCLUSIONS: Thrombectomy in patients with acute VBAO using the Trevo Stentriever™-either as the sole device or in conjunction with other devices-is feasible and seems to be similarly effective and safe as in the anterior circulation compared to reported data in the literature.

Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.

BACKGROUND: Rivaroxaban and dabigatran were not superior to aspirin in trials of patients with embolic stroke of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin in patients with ESUS and known risk factors for cardioembolism. METHODS: We conducted a multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale. Cardiac monitoring was mandatory, and aspirin treatment was switched to apixaban in case of atrial fibrillation detection. The primary outcome was any new ischemic lesion on brain magnetic resonance imaging (MRI) during 12-month follow-up. Secondary outcomes included major and clinically relevant nonmajor bleeding. RESULTS: A total of 352 patients were randomly assigned to receive apixaban (178 patients) or aspirin (174 patients) at a median of 8 days after ESUS. At 12-month follow-up, MRI follow-up was available in 325 participants (92.3%). New ischemic lesions occurred in 23 of 169 (13.6%) participants in the apixaban group and in 25 of 156 (16.0%) participants in the aspirin group (adjusted odds ratio, 0.79; 95% confidence interval, 0.42 to 1.48; P=0.57). Major and clinically relevant nonmajor bleeding occurred in five and seven participants, respectively (1-year cumulative incidences, 2.9 and 4.2; hazard ratio, 0.68; 95% confidence interval, 0.22 to 2.16). Serious adverse event rates were 43.9 per 100 person-years in those given apixaban and 45.7 per 100 person-years in those given aspirin. The Apixaban for the Treatment of Embolic Stroke of Undetermined Source trial was terminated after a prespecified interim analysis as a result of futility. CONCLUSIONS: Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers Squibb and Medtronic Europe; ClinicalTrials.gov number, NCT02427126.)

Combined systemic thrombolysis with alteplase and early hyperbaric oxygen therapy in experimental embolic stroke in rats: relationship to functional outcome and reduction of structural damage.

INTRODUCTION: The only causal therapy in ischemic stroke is thrombolysis with recombinant tissue plasminogen activator (rtPA), but it is feasible only for few patients, and new therapies are needed. This study investigates the effects of systemic thrombolysis with rtPA combined with hyperbaric oxygen therapy (HBOT) in embolic stroke in rats. METHODS: In 22 male Wistar rats, an embolic ischemic stroke was induced. The animals were randomized to one of four groups: control, thrombolysis alone, HBOT sequential or HBOT parallel with thrombolysis. HBOT (2.4 ATA, 1 h) started 45 min (sequential) or 120 min (parallel) after stroke. rtPA was given intravenously 120 min after stroke onset. Functional tests were performed after stroke induction and after treatment. After 6 h infarct volume and intracerebral hemorrhagic complications were assessed. RESULTS: Compared to the control group only the combination of HBOT and thrombolysis significantly improved the functional outcome (p=0.03) and reduced the infarct volume (p=0.01), whereas thrombolysis alone did not show a significant benefit. In all treatment groups there was a trend towards fewer hemorrhagic transformations. CONCLUSION: Hyperbaric oxygen in combination with thrombolysis shows neuroprotection in acute ischemic stroke in rats by reducing infarct volume and improving functional outcome in the early poststroke period.

Acute and long-term impairments regarding emotional symptoms and quality of life in patients suffering from transient ischemic attack and stroke.

Objectives: Ischemic stroke (IS) is often associated with long-lasting physical deficits, linked to emotional symptoms (ES) and lowered quality of life (QoL). However, recent observations raised doubts regarding the traditional perspective of solely impairment-driven ES. In fact, anxiety and depression were also reported after transient ischemic attack (TIA) with a per definition absence of infarction and thus lacking physical deficits. This study follows the hypothesis that TIA patients might exhibit non-physical symptoms affecting individual QoL.Methods: In a prospective single-center observational study, IS patients (n = 73) were compared with TIA patients (n = 24) regarding their neurological deficit, ES and QoL, whereas the latter were evaluated by the Hospital Anxiety and Depression Scale (HADS) and the Short Form 36 Heath Survey (SF-36). Assessments were conducted six times within a one-year follow-up period.Results: Overall, anxiety and depression decreased over time, while anxiety decreased more substantially. TIA patients showed similar levels of anxiety and depression when compared to IS patients. ES were detectable very early after the event and remained throughout the follow-up period in both groups. ES were associated with an impaired QoL including non-functional dimensions, while the strongest interrelations were observed for TIA patients, emphasizing interrelations between QoL and anxiety.Discussion: This study indicates that ES after TIA are comparable to the emotional burden after IS. ES after TIA were associated with QoL, pointing out their crucial role for individual well-being. Although confirmation in larger studies is necessary, these data underpin the need for early clinical awareness regarding non-physical symptoms in TIA patients.

A Combined Clinical and Serum Biomarker-Based Approach May Allow Early Differentiation Between Patients With Minor Stroke and Transient Ischemic Attack as Well as Mid-term Prognostication.

Background: Early differentiation between transient ischemic attack (TIA) and minor ischemic stroke (MIS) impacts on the patient's individual diagnostic work-up and treatment. Furthermore, estimations regarding persisting impairments after MIS are essential to guide rehabilitation programs. This study evaluated a combined clinical- and serum biomarker-based approach for the differentiation between TIA and MIS as well as the mid-term prognostication of the functional outcome, which is applicable within the first 24 h after symptom onset. Methods: Prospectively collected data were used for a retrospective analysis including the neurological deficit at admission (National Institutes of Health Stroke Scale, NIHSS) and the following serum biomarkers covering different pathophysiological aspects of stroke: Coagulation (fibrinogen, antithrombin), inflammation (C reactive protein), neuronal damage in the cellular [neuron specific enolase], and the extracellular compartment [matrix metalloproteinase-9, hyaluronic acid]. Further, cerebral magnetic resonance imaging was performed at baseline and day 7, while functional outcome was evaluated with the modified Rankin Scale (mRS) after 3, 6, and 12 months. Results: Based on data from 96 patients (age 64 ± 14 years), 23 TIA patients (NIHSS 0.6 ± 1.1) were compared with 73 MIS patients (NIHSS 2.4 ± 2.0). In a binary logistic regression analysis, the combination of NIHSS and serum biomarkers differentiated MIS from TIA with a sensitivity of 91.8% and a specificity of 60.9% [area under the curve (AUC) 0.84]. In patients with NIHSS 0 at admission, this panel resulted in a still acceptable sensitivity of 81.3% (specificity 71.4%, AUC 0.69) for the differentiation between MIS (n = 16) and TIA (n = 14). By adding age, remarkable sensitivities of 98.4, 100, and 98.2% for the prediction of an excellent outcome (mRS 0 or 1) were achieved with respect to time points investigated within the 1-year follow-up. However, the specificity was moderate and decreased over time (83.3, 70, 58.3%; AUC 0.96, 0.92, 0.91). Conclusion: This pilot study provides evidence that the NIHSS combined with selected serum biomarkers covering pathophysiological aspects of stroke may represent a useful tool to differentiate between MIS and TIA within 24 h after symptom onset. Further, this approach may accurately predict the mid-term outcome in minor stroke patients, which might help to allocate rehabilitative resources.

Outcomes of Hypothermia in Addition to Decompressive Hemicraniectomy in Treatment of Malignant Middle Cerebral Artery Stroke: A Randomized Clinical Trial.

Importance: Moderate hypothermia in addition to early decompressive hemicraniectomy has been suggested to further reduce mortality and improve functional outcome in patients with malignant middle cerebral artery (MCA) stroke. Objective: To investigate whether moderate hypothermia vs standard treatment after early hemicraniectomy reduces mortality at day 14 in patients with malignant MCA stroke. Design, Setting, and Participants: This randomized clinical trial recruited patients from August 2011 through September 2015 at 6 German university hospitals with dedicated neurointensive care units. Of the patients treated with hemicraniectomy and assessed for eligibility, patients were randomly assigned to either standard care or moderate hypothermia. Data analysis was completed from December 2016 to June 2018. Interventions: Moderate hypothermia (temperature, 33.0 ± 1.0°C) was maintained for at least 72 hours immediately after hemicraniectomy. Main Outcomes and Measures: The primary outcome was mortality rate at day 14 compared with the Fisher exact test and expressed as odds ratio (ORs) with 95% CIs. Rates of patients with serious adverse events were estimated for the period of the first 14 days after hemicraniectomy and 12 months of follow-up. Secondary outcome measures included functional outcome at 12 months. Results: Of the 50 study participants, 24 were assigned to standard care and 26 to moderate hypothermia. Twenty-eight were male (56%); the mean (SD) patient age was 51.3 (6.6) years. Recruitment was suspended for safety concerns: 12 of 26 patients (46%) in the hypothermia group and 7 of 24 patients (29%) receiving standard care had at least 1 serious adverse event within 14 days (OR, 2.05 [95% CI, 0.56-8.00]; P = .26); after 12 months, rates of serious adverse events were 80% (n = 20 of 25) in the hypothermia group and 43% (n = 10 of 23) in the standard care group (hazard ratio, 2.54 [95% CI, 1.29-5.00]; P = .005). The mortality rate at day 14 was 19% (5 of 26 patients) in the hypothermia group and 13% (3 of 24 patients) in the group receiving standard care (OR, 1.65 [95% CI, 0.28-12.01]; P = .70). There was no significant difference regarding functional outcome after 12 months of follow-up. Interpretation: In patients with malignant MCA stroke, moderate hypothermia early after hemicraniectomy did not improve mortality and functional outcome compared with standard care, but may cause serious harm in this specific setting. Trial Registration: http://www.drks.de, identifier DRKS00000623.

Author Correction: Identifying long-term stable refugia for relict plant species in East Asia.

In the original version of this Article, an incorrect sample size was provided for the number of relict species (443 instead of 442) and the number of relict forests (423 instead of 422). These errors have been corrected in both the PDF and HTML versions of the Article.

Identifying long-term stable refugia for relict plant species in East Asia.

Today East Asia harbors many "relict" plant species whose ranges were much larger during the Paleogene-Neogene and earlier. The ecological and climatic conditions suitable for these relict species have not been identified. Here, we map the abundance and distribution patterns of relict species, showing high abundance in the humid subtropical/warm-temperate forest regions. We further use Ecological Niche Modeling to show that these patterns align with maps of climate refugia, and we predict species' chances of persistence given the future climatic changes expected for East Asia. By 2070, potentially suitable areas with high richness of relict species will decrease, although the areas as a whole will probably expand. We identify areas in southwestern China and northern Vietnam as long-term climatically stable refugia likely to preserve ancient lineages, highlighting areas that could be prioritized for conservation of such species.

Mechanical thrombectomy versus systemic thrombolysis in MCA stroke: a distance to thrombus-based outcome analysis.

BACKGROUND: Acute ischemic stroke due to occlusion of the middle cerebral artery (MCA) has a poor outcome. The distance to thrombus (DT) from the carotid T can predict the outcome after intravenous thrombolysis (IVT). With a DT <16 mm, fewer than 50% of patients treated with IVT have a favorable outcome. OBJECTIVE: To compare stent retriever-based endovascular mechanical thrombectomy (MT) plus additional IVT (IVT-MT) with IVT alone. MATERIALS AND METHODS: Patients with MCA occlusion proved by CT angiography with a DT <16 mm, treated with either IVT alone or with stent retriever-based endovascular IVT-MT, were included in this study. Changes in National Institutes of Health Stroke Scale (NIHSS), the 7-day NIHSS, and the 90-day modified Rankin Scale (mRS) scores were analyzed by treatment modality. RESULTS: Of 621 patients, 87 fulfilled all inclusion criteria. Fifty-nine patients were treated with IVT and 28 with IVT-MT. Although patients treated with IVT-MT had had significantly more severe strokes than those treated with IVT alone (initial NIHSS 16 (7-18) vs 14 (5-22); p=0.032), both the short- and long-term outcomes were significantly better in this patient group (NIHSS improvement on day 7: 10.9±6.3 vs 6.7±6.7; p=0.008/90-day mRS: 2 (0.75-2.5) vs 4 (2-6); p=0.003). CONCLUSIONS: In patients with an acute MCA occlusion and a DT <16 mm, IVT-MT leads to a significantly better outcome than in patients treated with IVT alone.

Does treatment with t-PA increase the risk of developing epilepsy after stroke?

Patients suffering from ischemic stroke carry an enhanced risk of developing secondary epilepsy. We sought to clarify whether thrombolytic treatment with recombinant tissue plasminogen activator (t-PA) is independently associated with post-stroke epilepsy (PSE). In this observational study, data from 302 stroke patients treated at a single academic neurological department were analyzed retrospectively. Median follow-up was 42 months (maximum 80). Variables included presence of comorbidity, stroke severity, neurological presentation, complications, infarct characteristics, and treatment with t-PA. After univariate analyses, a multivariate analysis was performed to create a model of factors that were significantly associated with PSE, including treatment with t-PA. 13.9 % of patients developed PSE during follow-up. Multivariate analysis identified 5 independent factors for PSE: low Barthel Index at discharge; hemianopia; infection acquired during the hospital stay; involvement of the temporal lobe; involvement of the perirolandic cortex. While the incidence of PSE was higher in patients treated with t-PA (20.6 vs. 10.7 %, univariate analysis; p = 0.020), the effect was lost after adjusting for several factors associated with t-PA treatment [odds ratio for PSE after treatment with t-PA 1.3 (95 % CI 0.6-2.9), p = 0.489]. This study failed to identify treatment with t-PA as an independent risk factor for PSE.

A novel approach for mechanical tissue characterization indicates decreased elastic strength in brain areas affected by experimental thromboembolic stroke.

As treatment of ischemic stroke remains a challenge with respect to the failure of numerous neuroprotective attempts, there is an ongoing need for better understanding of pathophysiological mechanisms causing tissue damage. Although ischemic outcomes have been studied extensively at the cellular and molecular level using histological and biochemical methods, properties of ischemia-affected brain tissue with respect to mechanical integrity have not been addressed so far. As a novel approach, this study used fluorescence-based detection of regions affected by experimental thromboembolic stroke in combination with scanning force microscopy to examine mechanical alterations in selected rat brain areas. Twenty-five hours after onset of ischemia, a decreased elastic strength in the striatum as the region primarily affected by ischemia was found compared with the contralateral nonaffected hemisphere. Additional intrahemispheric analyses showed decreased elastic strength in the ischemic border zone compared with the more severely affected striatum. In conclusion, these data strongly indicate a critical alteration in mechanical tissue integrity caused by focal cerebral ischemia. Further, on the basis of data that have been obtained in relation to the ischemic border zone, a shell-like pattern of mechanical tissue damage was found in good accordance with the penumbra concept. These findings might enable the development of specific therapeutic interventions to protect affected areas from critical loss of mechanical integrity.

DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke (DEPTH-SOS): a protocol of a multicenter randomized controlled clinical trial and a literature review.

RATIONALE: Although decompressive hemicraniectomy clearly reduces mortality in severe space-occupying middle cerebral artery infarction (so-called malignant middle cerebral artery infarction), every fifth patient still dies in the acute phase and every third patient is left with moderate to severe disability. Therapeutic hypothermia is a neuroprotective and antiedematous treatment option that has shown promising effects in severe stroke. A combination of both treatment strategies may have the potential to further reduce mortality and morbidity in malignant middle cerebral artery infarction, but needs evaluation of its efficacy within the setting of a randomized clinical trial. AIMS: The DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke (DEPTH-SOS) trial aims to investigate safety and feasibility of moderate therapeutic hypothermia (33°C ± 1) over at least 72 h in addition to early decompressive hemicraniectomy (≤48 hours after symptom onset) in patients with malignant middle cerebral artery infarction. DESIGN: The DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke is a prospective, multicenter, open, two-arm (1:1) comparative, randomized, controlled trial. STUDY OUTCOMES: The primary end-point is mortality at day 14. The secondary end-points include functional outcome at day 14 and at 12 months follow-up, and complications related to hypothermia. DISCUSSION: The results of this trial will provide data on safety and feasibility of moderate hypothermia in addition to decompressive hemicraniectomy in malignant middle cerebral artery infarction. Furthermore, efficacy data on early mortality and long-term functional outcome will be obtained, forming the basis of subsequent trials.