Blood pressure declines and less favorable outcomes in the NINDS tPA stroke study

BACKGROUND AND PURPOSE: Hypertension is the most important modifiable risk factor for secondary stroke prevention but the immediate management of blood pressure after stroke is uncertain. We evaluated outcomes in the NINDS tPA stroke study in relation to blood pressure declines during the first 24 h after randomization. METHODS: Declines in blood pressure compared to baseline and preceding time points were analyzed in relationship to favorable outcomes (by a global test), poor outcomes (Rankin scale >3) and death at 3 months. RESULTS: 551 patients did not receive immediate pre-randomization anti-hypertensive treatment and had available blood pressures. Multivariate analysis showed significantly and progressively reducing likelihoods of a favorable outcome with each 10 mmHg decline in systolic blood pressure (SBP) >50 mmHg compared to any preceding measurement. Poor outcomes were significantly more likely in patients with >50 mmHg SBP reduction (or >30 mmHg compared to any immediately preceding measurement). There was an increased risk of death with blood pressure declines >60 mmHg. tPA treatment still produced favorable outcomes compared with placebo even with blood pressure declines. The median largest SBP reduction from baseline in patients treated with tPA was 35 mmHg compared to 30 mmHg in placebo-treated patients (p<0.01). CONCLUSIONS: In this post hoc analysis, progressively reducing likelihoods of a favorable outcome were seen with increasing declines in SBP. Despite a greater likelihood of favorable outcomes, tPA treatment was associated with a greater reduction in blood pressure than placebo. Randomized trials of blood pressure management are needed.     

Hyperglycemia during ischemia rapidly accelerates brain damage in stroke patients treated with tPA.

To evaluate impact of glucose burden on diffusion-weighted imaging (DWI)-lesion evolution according to ischemia duration in stroke. We studied 47 patients with transcranial Doppler (TCD)-documented artery occlusion treated with intravenous tissue plasminogen activator. Hyperglycemia (HG) was defined as glucose>140 mg/dL. A subcutaneous device continuously monitored glucose during 24 h. Magnetic resonance imaging was performed pretreatment (1) and at 24 to 36 h (2) in 30 patients. We measured initial PWI lesion (PW1) and DWI growth: DW2-DW1 (DWg). Serial TCD during 24 h determined occlusion time (OT). National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 48 h. Poor short-term clinical course defined as <50% recovery of initial NIHSS. Baseline NIHSS was 18. On admission 10 patients (21.3%) were hyperglycemic and presented similar NIHSS, DW1, and PW1 lesion extension as those without HG. During monitoring 24 patients (51%) had HG, 21 (45%) of them during OT (median OT 12 h). Median 48 h-NIHSS was 10; 15 patients presented poor outcome. 48 h-NIHSS was higher in patients with HG during OT (15 versus 3; P<0.001). Patients with favorable outcome had shorter OT (8.4 versus 17.4 h; P<0.001). However, the only independent predictor of poor outcome was HG during OT (OR: 20.3; 95% CI: 3.77 to 108.8; P<0.001). At 24 h mean DWg was 52 cm(3). A receiver operating characteristic curve identified DWg>14 cm(3) best predictor of poor outcome (sensitivity, 85.7%; specificity, 75%). Total OT (P=0.007) and HG during OT (P=0.01) showed the strongest correlation with DWg. DWI lesion grew 2.7 times faster in patients with HG than without HG during OT (1.73 versus 4.63 cm(3)/h of occlusion; P=0.07). In a regression model the only independent predictor of DWg was HG during OT (OR: 10.83; 95% CI: 1.96 to 59.83; P=0.006). Hyperglycemia, especially during OT, has a powerful deleterious effect after stroke accelerating brain damage.     

Pavia Memory Project: Study design and first results

This paper describes the design and first results of the cross-sectional phase of a study on memory impairment in elderly subjects (Pavia Memory Project). The target population consisted of the 1,046 subjects born in 1925 and currently living in Pavia. Four hundred and thirty-six subjects (plus 287 interviewed at home) participated in the first stage, which consisted of a semistructured anamnestic interview. The 400 interviewed subjects with none of the exclusion criteria participated in the second stage, which consisted of a memory test battery, a standardized neurological examination and screening procedures for depression (GDS) and dementia (MMSE). On the basis of the memory scores, three groups were defined: memory impairment (MI: 8.8%), mild memory impairment (MMI: 39.8%); normal (N: 51.3%). There were more failures on the visuo-spatial memory tests. Depression was equally distributed in the N and MI groups (about 15%), but was more frequent in the MMI group (27%). Abnormal neurological signs were largely independent of memory performance. Two cohorts (of MI and N subjects) underwent neuropsychological and instrumental (CT-scan, EEG, ERPs, eye movements) assessment, which will be regularly repeated in the longitudinal phase.

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Sommario Viene presentato il disegno di uno studio sui disturbi mnesici del soggetto anziano (Progetto Pavia Memoria) e vengono riportati i primi risultati relativi alla fase trasversale. La popolazione in studio era rappresentata dai 1046 soggetti nati nel 1925 e residenti a Pavia. 436 soggetti (più 287 intervistati a domicilio) hanno partecipato al primo stadio che consisteva in una intervista semistrutturata per la raccolta di dati anamnestici. 400 soggetti che non presentavano criteri di esclusione hanno partecipato al secondo stadio che consisteva in una batteria di test di memoria, in un esame neurologico standardizzato e in procedure di screening per la depressione (GDS) e la demenza (MMSE). Sulla base dei punteggi ottenuti ai test mnesici sono stati definiti tre gruppi di soggetti: disturbo mnesico (MI: 8.8%); disturbo mnesico lieve (MMI: 39.8%) e normali (N: 51.3%). I test di memoria visuo-spaziale sono risultati alterati con maggiore frequenza. La depressione era ugualmente distribuita nei gruppi MI e N (circa 15%), ma era più frequente nel gruppo MMI. La presenza di segni patologici all'esame neurologico era per lo più indipendente dalle prestazioni mnesiche.Due coorti (di soggetti MI e N) sono state sottoposte a valutazioni neuropsicologiche e strumentali (TC, EEG, potenziali evento-correlati, movimenti oculari) che verranno ripetute a regolari intervalli nella fase longitudinale.

     

Non-convulsive status epilepticus after ischemic stroke: a hospital-based stroke cohort study

To evaluate in the setting of a stroke unit ward the usefulness of a prolonged (>6 h) video-EEG recording (PVEEG) in identifying non-convulsive status epilepticus (NCSE) in patients with an acute ischemic stroke. Predictors of NCSE were also evaluated. Patients with an acute ischemic stroke, referred to our unit, were included in this prospective observational study. A PVEEG recording was implemented after stroke in all patients during the first week: (a) promptly in those exhibiting a clear or suspected epileptic manifestation; (b) at any time during the routine activity in the remaining patients. After the first week, a standard EEG/PVEEG recording was hooked up only in presence of an evident or suspected epileptic manifestation or as control of a previous epileptic episode. NCSE was identified in 32 of the 889 patients (3.6 %) included in the study. It occurred early (within the first week) in 20/32 (62.5 %) patients and late in the remaining 12. Diagnosis was made on the basis of a specific clinical suspect (n = 19, 59.4 %) or without any suspect (n = 13, 40.6 %). In a multivariate analysis, a significant association of NCSE was observed with NIHSS score, infarct size and large atherothrombotic etiology. NCSE is not a rare event after an acute ischemic stroke and a delayed diagnosis could worsen patient prognosis. Since NCSE can be difficult to be diagnosed only on clinical grounds, implementation of a prompt PVEEG should be kept available in a stroke unit whenever a patient develop signs, although subtle, consistent with NCSE.     

Argatroban plus aspirin versus aspirin in acute ischemic stroke

Objectives: Anticoagulant therapy in the acute phase of AIS remains controversial. The aim of this study was to investigate whether argatroban benefited early stroke outcomes compared with antiplatelet treatment.

Methods: We reviewed data from 1,485 patients with AIS hospitalized at Tianjin Union Medical Center (TUMC) between 1 January 2013 and 31 December 2015 from the TUMC registry database. Patients were divided into two groups: an antiplatelet group (aspirin 300 mg daily) and an argatroban group (argatroban 60 mg for 2 days followed by 20 mg daily; or 20 mg daily – both regimens combination with aspirin 100 mg daily). Two primary outcomes, change in NIHSS score (baseline–discharge) and intracerebral hemorrhage, were investigated.

Results: No major symptomatic intracerebral hemorrhages were observed in either group. Both groups had significantly decreased NIHSS scores at discharge (Z = ?14.617, P < 0.001 and Z = ?6.385, P < 0.001, respectively), and there were no significant group differences in NIHSS score change (Z = ?1.888, P = 0.059). In the mild stroke subgroup, the argatroban group had a worse NIHSS score at discharge (Z = ?6.148, P = 0.002), while the aspirin group had an improved NIHSS score (Z = ?4,423, P < 0.001). In the moderate stroke subgroup, both groups had significantly decreased NIHSS scores at discharge (Z = ?13.260, P < 0.001 and Z = ?7.108, P < 0.001, respectively) and there were no significant group differences in NIHSS score changes (Z = ?1.888, P = 0.059).

Conclusion: Argatroban is effective and safe for the treatment of moderate AIS with similar efficacy to high-dose aspirin in the acute phase of AIS, although no additional benefit on short-term outcome was observed. For patients with mild AIS, argatroban may be inferior to high-dose aspirin.     

High risk cohort study for psychiatric disorders in childhood: rationale,design, methods and preliminary results

The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders. We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random =958; high risk =1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high‐risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub‐sample with “high risk” for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information. Copyright © 2014 John Wiley & Sons, Ltd.     

Age at school entry and reported symptoms of attention-deficit/hyperactivity in first graders: results of the prospective cohort study ikidS

Young age at school entry (ASE) is related to attention-deficit/hyperactivity disorder in higher grades. The reason for this association is unclear, but medical oversupply and stress-related factors are discussed. We aimed to investigate whether ASE is associated with reported symptoms of attention-deficit/hyperactivity (ADH) already in first grade. Data of a population-based prospective cohort study (N = 2003; Mainz-Bingen region; Rhineland-Palatinate; Germany) with baseline assessments prior to school entry and two follow-ups during first grade were analysed. ADH symptoms were assessed by parent and teacher versions of the Strengths and Difficulties Questionnaire. Associations between ASE and scores of the hyperactivity/inattention subscale (range 0–10) were investigated by regression analysis and adjusted for potential confounders and baseline symptoms prior to school entry. In total, 1633 children (52% boys, mean ASE 6.5 years) were included. There were no relationships between ASE and parent-reported scores of the hyperactivity/inattention subscale prior to school entry and 3 months thereafter. However, at the end of first grade, ASE was negatively associated with the hyperactivity/inattention subscale in parent (− 0.7 subscale points per year ASE, standard error = 0.16, p < 0.0001) and teacher reports (− 1.2 subscale points per year ASE, standard error = 0.25, p < 0.0001). This ASE effect appeared more pronounced in girls than in boys. Young ASE is related to more reported symptoms of ADH at the end of first grade, but not before. The evolvement of this effect during first grade may be a clue to ASE-related stress factors.

     

tPA by telephone: extending the benefits of a comprehensive stroke center

The use of tissue plasminogen activator (tPA) in community hospitals has been limited by a lack of neurologic support. The authors developed a telephone network to support community emergency departments (EDs) in the use of tPA. Their experience demonstrates equivalent results for patients treated by telephone and those treated in-house. Their number of tPA-treated patients increased 72%. Requirements included willingness of community EDs to use tPA and willingness of the stroke center to provide support.     

Using tPA for acute stroke in a rural setting

Controversy continues regarding the safety and efficacy of tissue plasminogen activator (tPA) for stroke outside major centers. We reviewed charts from 1998 to 2004 of 493 patients admitted with TIA or stroke to our small rural hospital. There was a 4% tPA treatment rate with no symptomatic intracranial hemorrhage and zero mortality. IV tPA can be safe and effective in the treatment of acute stroke despite the size of the institution.     

Dysphagia-related acute stroke complications: A retrospective observational cohort study

ObjectivesPost-stroke dysphagia is associated with aspiration pneumonia, but strategies intended to mitigate this complication, such as oral intake modifications, may unintentionally lead to dehydration-related complications such as urinary tract infections (UTIs) and constipation. This study aimed to determine the rates of aspiration pneumonia, dehydration, UTI and constipation in a large cohort of acute stroke patients and the independent predictors of each complication.Materials and methodsData were extracted retrospectively for 31,953 acute stroke patients admitted to six hospitals in Adelaide, South Australia over a 20-year period. Tests of difference compared rates of complications between patients with and without dysphagia. Multiple logistic regression modelling explored variables that significantly predicted each complication.ResultsIn this consecutive cohort of acute stroke patients, with a mean (SD) age of 73.8 (13.8) years and 70.2% presenting with ischaemic stroke, rates of complications were: aspiration pneumonia (6.5%); dehydration (6.7%); UTI (10.1%); and constipation (4.4%). Each complication was significantly more prevalent for patients with dysphagia compared to those without. Controlling for demographic and other clinical variables, the presence of dysphagia independently predicted aspiration pneumonia (OR=2.61, 95% CI 2.21-3.07; p<.001), dehydration (OR=2.05, 95% CI 1.76-2.38; p<.001), UTI (OR=1.34, 95% CI 1.16-1.56; p<.001), and constipation (OR=1.30, 95% CI 1.07-1.59; p=.009). Additional predictive factors were increased age and prolonged hospitalisation.ConclusionsAspiration pneumonia, dehydration, UTI, and constipation are common acute sequelae of stroke and independently associated with dysphagia. Future dysphagia intervention initiatives may utilise these reported complication rates to evaluate their impact on all four adverse health complications.