Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke.

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS: Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

Topographical distribution of perioperative cerebral infarction associated with transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is associated with a high incidence of cerebrovascular injury. As these injuries are thought to be primarily embolic, neuroprotection strategies have focused on embolic protection devices. However, the topographical distribution of cerebral emboli and how this impacts on the effectiveness of these devices have not been thoroughly assessed. Here, we evaluated the anatomical characteristics of magnetic resonance imaging (MRI)-defined cerebral ischemic lesions occurring secondary to TAVI to enhance our understanding of the distribution of cardioembolic phenomena. METHODS: Forty patients undergoing transfemoral TAVI with an Edwards SAPIEN-XT valve under general anesthesia were enrolled prospectively in this observational study. Participants underwent brain MRI preprocedure, and 3 ± 1 days and 6 ± 1 months postprocedure. RESULTS: Mean ± SD participant age was 82 ± 7 years. Patients had an intermediate to high surgical risk, with a mean Society of Thoracic Surgeons score of 6.3 ± 3.5 and EuroSCORE of 18.1 ± 10.6. Post-TAVI, there were no clinically apparent cerebrovascular events, but MRI assessments identified 83 new lesions across 19 of 31 (61%) participants, with a median ± interquartile range number and volume of 1 ± 2.8 lesions and 20 ± 190 µL per patient. By volume, 80% of the infarcts were cortical, 90% in the posterior circulation and 81% in the right hemisphere. CONCLUSIONS: The distribution of lesions that we detected suggests that cortical gray matter, the posterior circulation, and the right hemisphere are all particularly vulnerable to perioperative cerebrovascular injury. This finding has implications for the use of intraoperative cerebral embolic protection devices, particularly those that leave the left subclavian and, therefore, left vertebral artery unprotected.

Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study.

Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. Study design EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. Study outcomes The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration ClinicalTrials.gov NCT02388061.

UV-Vis spectrophotometry of quinone flow battery electrolyte for in situ monitoring and improved electrochemical modeling of potential and quinhydrone formation.

Quinone-based aqueous flow batteries provide a potential opportunity for large-scale, low-cost energy storage due to their composition from earth abundant elements, high aqueous solubility, reversible redox kinetics and their chemical tunability such as reduction potential. In an operating flow battery utilizing 9,10-anthraquinone-2,7-disulfonic acid, the aggregation of an oxidized quinone and a reduced hydroquinone to form a quinhydrone dimer causes significant variations from ideal solution behavior and of optical absorption from the Beer-Lambert law. We utilize in situ UV-Vis spectrophotometry to establish (a), quinone, hydroquinone and quinhydrone molar attenuation profiles and (b), an equilibrium constant for formation of the quinhydrone dimer (KQHQ) ∼ 80 M-1. We use the molar optical attenuation profiles to identify the total molecular concentration and state of charge at arbitrary mixtures of quinone and hydroquinone. We report density functional theory calculations to support the quinhydrone UV-Vis measurements and to provide insight into the dimerization conformations. We instrument a quinone-bromine flow battery with a Pd-H reference electrode in order to demonstrate how complexation in both the negative (quinone) and positive (bromine) electrolytes directly impacts measured half-cell and full-cell voltages. This work shows how accounting for electrolyte complexation improves the accuracy of electrochemical modeling of flow battery electrolytes.

Neurological Injury in Intermediate-Risk Transcatheter Aortic Valve Implantation.

BACKGROUND: The application of transcatheter aortic valve implantation (TAVI) to intermediate-risk patients is a controversial issue. Of concern, neurological injury in this group remains poorly defined. Among high-risk and inoperable patients, subclinical injury is reported on average in 75% undergoing the procedure. Although this attendant risk may be acceptable in higher-risk patients, it may not be so in those of lower risk. METHODS AND RESULTS: Forty patients undergoing TAVI with the Edwards SAPIEN-XT™ prosthesis were prospectively studied. Patients were of intermediate surgical risk, with a mean±standard deviation Society of Thoracic Surgeons score of 5.1±2.5% and a EuroSCORE II of 4.8±2.4%; participant age was 82±7 years. Clinically apparent injury was assessed by serial National Institutes of Health Stroke Scale assessments, Montreal Cognitive Assessments (MoCA), and with the Confusion Assessment Method. These identified 1 (2.5%) minor stroke, 1 (2.5%) episode of postoperative delirium, and 2 patients (5%) with significant postoperative cognitive dysfunction. Subclinical neurological injury was assessed using brain magnetic resonance imaging, including diffusion-weighted imaging (DWI) sequences preprocedure and at 3±1 days postprocedure. This identified 68 new DWI lesions present in 60% of participants, with a median±interquartile range of 1±3 lesions/patient and volumes of infarction of 24±19 µL/lesion and 89±218 µL/patient. DWI lesions were associated with a statistically significant reduction in early cognition (mean ΔMoCA -3.5±1.7) without effect on cognition, quality of life, or functional capacity at 6 months. CONCLUSIONS: Objectively measured subclinical neurological injuries remain a concern in intermediate-risk patients undergoing TAVI and are likely to manifest with early neurocognitive changes. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Australian & New Zealand Clinical Trials Registry: ACTRN12613000083796.

The epidemiology of silent brain infarction: a systematic review of population-based cohorts.

BACKGROUND: Cerebral infarction is a commonly observed radiological finding in the absence of corresponding, clinical symptomatology, the so-called silent brain infarction (SBI). SBIs are a relatively new consideration as improved imaging has facilitated recognition of their occurrence. However, the true incidence, prevalence and risk factors associated with SBI remain controversial. METHODS: Systematic searches of the Medline and EMBASE databases from 1946 to December 2013 were performed to identify original studies of population-based adult cohorts derived from community surveys and routine health screening that reported the incidence and prevalence of magnetic resonance imaging (MRI)-determined SBI. RESULTS: The prevalence of SBI ranges from 5% to 62% with most studies reported in the 10% to 20% range. Longitudinal studies suggest an annual incidence of between 2% and 4%. A strong association was seen to exist between epidemiological estimates of SBI and age of the population assessed. Hypertension, carotid stenosis, chronic kidney disease and metabolic syndrome all showed a strong association with SBI. Heart failure, coronary artery disease, hyperhomocysteinemia and obstructive sleep apnea are also likely of significance. However, any association between SBI and gender, ethnicity, tobacco or alcohol consumption, obesity, dyslipidemia, atrial fibrillation and diabetes mellitus remains unclear. CONCLUSIONS: SBI is a remarkably common phenomenon and endemic among older people. This systematic review supports the association of a number of traditional vascular risk factors, but also highlights disparities between clinically apparent and silent strokes, potentially suggesting important differences in pathophysiology and warranting further investigation.

Vertebrobasilar dissections: case series comparing patients with and without dissecting aneurysms.

Vertebrobasilar dissections are being increasingly diagnosed due to better awareness and increased availability of modern imaging techniques of the intracranial and extracranial arteries. The clinical presentation and outcome in patients with vertebrobasilar dissections may be complicated by dissecting aneurysms. The aim of this retrospective study was to compare the clinical profile of patients with vertebrobasilar dissections with and without dissecting aneurysms, and to determine predisposing factors to the development of aneurysms. Thirty patients (19 [63%] male; median age 44.5 years) were identified. The patients were divided into two groups, an aneurysmal dissection group with seven patients and a non-aneurysmal dissection group with 23 patients. Eight (27%) patients presented with dissection after trivial trauma, three (10%) following high-speed vehicular trauma, two (7%) were associated with infection, but most (57%) were apparently spontaneous. Migraine with aura (p=0.008) and female sex (p=0.03) were observed more frequently in the aneurysmal dissection group. Though vascular risk factors other than hypertension and atrial fibrillation were seen in a greater percentage of patients in the non-aneurysmal dissection group, this was not statistically significant. Patients were treated with antiplatelet agents (n=8) or warfarin (n=13) or underwent an endovascular intervention (n=6). Post-discharge data were available in 19 patients, of whom 14 (74%) were independent at a median follow-up of 4 months. Female sex and migraine with aura may predispose to the formation of acute dissecting aneurysms and this requires further research. Larger, prospective studies are required to ascertain epidemiologic and etiologic factors predisposing patients to the development of both intracranial and extracranial dissecting aneurysms in the vertebrobasilar circulation.

A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA).

BACKGROUND AND HYPOTHESIS: Thrombolysis with tissue plasminogen activator is proven to reduce disability when given within 4·5 h of ischemic stroke onset. However, tissue plasminogen activator only succeeds in recanalizing large vessel arterial occlusion in a minority of patients. We hypothesized that anterior circulation ischemic stroke patients, selected with 'dual target' vessel occlusion and evidence of salvageable brain using computed tomography or magnetic resonance imaging 'mismatch' within 4·5 h of onset, would have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone. STUDY DESIGN: EXTEND-IA is an investigator-initiated, phase II, multicenter prospective, randomized, open-label, blinded-endpoint study. Ischemic stroke patients receiving standard 0·9 mg/kg intravenous tissue plasminogen activator within 4·5 h of stroke onset who have good prestroke functional status (modified Rankin Scale <2, no upper age limit) will undergo multimodal computed tomography or magnetic resonance imaging. Patients who also meet dual target imaging criteria: vessel occlusion (internal carotid or middle cerebral artery) and mismatch (perfusion lesion : ischemic core mismatch ratio >1·2, absolute mismatch >10 ml, ischemic core volume <70 ml) will be randomized to either clot retrieval with the Solitaire FR device after full dose intravenous tissue plasminogen activator, or tissue plasminogen activator alone. STUDY OUTCOMES: The coprimary outcome measure will be reperfusion at 24 h and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1) at day 3. Secondary outcomes include modified Rankin Scale at day 90, death, and symptomatic intracranial hemorrhage.

Cobalt toxicity--an emerging clinical problem in patients with metal-on-metal hip prostheses?

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market.

Early changes in physiological variables after stroke.

Several aspects of physiology, notably blood pressure, body temperature, blood glucose, and blood oxygen saturation, may be altered after an ischemic stroke and intracerebral hemorrhage. Generally, blood pressure and temperature rise acutely after a stroke, before returning to normal. Blood glucose and oxygen levels may be abnormal in individuals, but they do not follow a set pattern. Several aspects of these physiological alterations remain unclear, including their principal determinants - whether they genuinely affect prognosis (as opposed to merely representing underlying processes such as inflammation or a stress response), whether these effects are adaptive or maladaptive, whether the effects are specific to certain subgroups (e.g. lacunar stroke) and whether modifying physiology also modifies its prognostic effect. Hypertension and hyperglycemia may be helpful or harmful, depending on the perfusion status after an ischemic stroke; the therapeutic response to their lowering may be correspondingly variable. Hypothermia may provide benefits, in addition to preventing harm through protection from hyperthermia. Hypoxia is harmful, but normobaric hyperoxia is unhelpful or even harmful in normoxic patients. Hyperbaric hyperoxia, however, may be beneficial, though this remains unproven. The above-mentioned uncertainties necessitate generally conservative measures for physiology management, although there are notably specific recommendations for thrombolysis-eligible patients. Stroke unit care is associated with better outcome, possibly through better management of poststroke physiology. Stroke units can also facilitate research to clarify the relationship between physiology and prognosis, and to subsequently clarify management guidelines.

The time course and determinants of blood pressure within the first 48 h after ischemic stroke.

BACKGROUND AND PURPOSE: Previous research suggests that blood pressure falls acutely after ischemic stroke. We aimed to further characterize this fall with a statistical technique that allows the application of regression techniques to serial blood pressure outcome data. METHODS: In a prospectively recruited ischemic stroke cohort, systolic (SBP) and diastolic (DBP) blood pressure was recorded every 4 h until 48 h after stroke. Potential determinants of blood pressure, including stroke severity and acute infection, were also recorded. Mixed effects models were used to model serial blood pressure measurements over time, adjusted for significant determinants. RESULTS: In 156 patients, SBP and DBP fell by 14.9 mm Hg (95% CI 6.2-22.6 mm Hg) and 6.2 mm Hg (95% CI 1.4-10.6 mm Hg), respectively, over the first 48 h after stroke. SBP was higher in patients with premorbid hypertension, a previous history of stroke or TIA, current alcohol use, increasing age, stroke of mild to moderate severity (NIHSS 3-13) and in patients treated with antihypertensives. SBP was lower in smokers. There was a progressive rise in SBP in patients with acute infection. No factors other than time were associated with DBP. CONCLUSIONS: The use of mixed effects models has identified a linear SBP and DBP fall over the first 48 h after stroke. The timing and magnitude of this fall should be accounted for in the design of future prognostic and intervention studies.

The time course and determinants of temperature within the first 48 h after ischaemic stroke.

BACKGROUND AND PURPOSE: Previous research has attempted to analyze the relationship between post-stroke hyperthermia and prognosis. These analyses have been hindered by a lack of information about the time course and determinants of temperature change after stroke. METHODS: Serial temperatures were measured until 48 h after ischaemic stroke in a prospectively recruited cohort. Potential determinants of temperature, including stroke severity [measured using the National Institutes of Health Stroke Scale (NIHSS)], infection and paracetamol use were recorded. Mixed-effects models were used to model serial temperature measurements over time, adjusted for significant determinants. RESULTS: In 155 patients the mean temperature rose from 36.5 degrees C at the time of stroke to 36.7 degrees C approximately 36 h later. The factors with significant multivariable associations with serial temperatures were: first- and second-order time components, infection, paracetamol administration and the interaction between stroke severity (NIHSS > or =6) and time (all p < 0.1). Patients with admission NIHSS > or =6 had a mean temperature rise of 0.35 degrees C during the first 36 h after stroke, compared with a rise of 0.17 degrees C in those with NIHSS < or =5. CONCLUSIONS: Temperature spontaneously rises during the first 36 h after stroke, particularly after severer stroke and in the presence of infection.

Circadian blood pressure variation after acute stroke.

We aimed to characterise the patterns of circadian blood pressure (BP) variation after acute stroke and determine whether any relationship exists between these patterns and stroke outcome. BP was recorded manually every 4 h for 48 h following acute stroke. Patients were classified according to the percentage fall in mean systolic BP (SBP) at night compared to during the day as: dippers (fall > or = 10-<20%); extreme dippers (> or = 20%); non-dippers (> or = 0-<10%); and reverse dippers (<0%, that is, a rise in mean nocturnal SBP compared to mean daytime SBP). One hundred and seventy-three stroke patients were included in the study (83 men, 90 women; mean age 74.3 years). Four patients (2.3%) were extreme dippers, 25 (14.5%) dippers, 80 (46.2%) non-dippers and 64 (36.9%) reverse dippers. There was a non-significant trend in the proportion of patients who were dead or dependent at 3 months in the extreme dipper (p=0.59) and reverse dipper (p=0.35) groups. Non-dipping and reverse-dipping were relatively common patterns of circadian BP variation seen in acute stroke patients. These patterns were not clearly associated with outcome.

The effect of admission physiological variables on 30 day outcome after stroke.

INTRODUCTION: Potentially modifiable physiological variables may influence stroke prognosis but their independence from modifiable factors remains unclear. METHODS: Admission physiological measures (blood pressure, heart rate, temperature and blood glucose) and other unmodifiable factors were recorded from patients presenting within 48 hours of stroke. These variables were compared with the outcomes of death and death or dependency at 30 days in multivariate statistical models. RESULTS: In the 186 patients included in the study, age, atrial fibrillation and the National Institutes of Health Stroke Score were identified as unmodifiable factors independently associated with death and death or dependency. After adjusting for these factors, none of the physiological variables were independently associated with death, while only diastolic blood pressure (DBP) > or = 90 mmHg was associated with death or dependency at 30 days (p = 0.02). CONCLUSIONS: Except for elevated DBP, we found no independent associations between admission physiology and outcome at 30 days in an unselected stroke cohort. Future studies should look for associations in subgroups, or by analysing serial changes in physiology during the early post-stroke period.

Impact of premorbid undernutrition on outcome in stroke patients.

BACKGROUND AND PURPOSE: To assess the prevalence of premorbid undernutrition and its impact on outcomes 1 month after stroke. METHODS: The study recruited from consecutive stroke admissions during a 10-month period. Premorbid nutritional status (using the subjective global assessment [SGA]), premorbid functioning (modified Rankin scale [MRS]), and stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) were assessed at admission. The associations between premorbid nutritional status, poor outcome (defined as MRS > or =3), and mortality were examined before and after adjustment for confounding variables, including age, gender, stroke risk factors, stroke severity, and admission serum albumin. RESULTS: Thirty of 185 patients were assessed as having undernutrition at admission. Significant unadjusted associations were observed between undernutrition and poor outcome (odds ratio [OR], 3.4; 95% CI, 1.3 to 8.7; P=0.01), and mortality (OR, 3.1, 95% CI, 1.3 to 7.7; P=0.02) at 1 month. NIHSS, age, and premorbid MRS were also significantly associated with poor outcomes. After adjustment for these factors, the effect size of associations remained important but not significant (poor outcome: OR, 2.4; 95% CI, 0.7 to 9.0, P=0.18; mortality: OR, 3.2; 95% CI, 1.0 to 10.4, P=0.05). CONCLUSIONS: Premorbid undernutrition, as assessed using the SGA, appears to be an independent predictor of poor stroke outcome. Stroke prevention strategies should target undernutrition in the population at risk for stroke to improve outcomes.