Neurozaštita u akutnom moždanom udaru: ima li još nade?

Efficacious treatment of acute stroke is a major challenge in modern medicine. Therapeutic neuroprotection acting towards minimization of ischemic neuronal injury in penumbral tissue in the regions of reduced cerebral blood flow seems to be an appealing concept in the treatment of acute stroke and brain trauma. The ‘ischemic cascade’, a complex mechanism of metabolic events initiated by brain ischemia, offers many pathways by which the neuroprotective agents may act. Time to treatment remains a major limiting factor for many potential neuroprotective agents. Although the exact therapeutic window is not known, evidence from many animal models and clinical research suggest that neuroprotective therapy can only be efficacious if administered very early after the onset of ischemia. Various neuroprotective agents have been tested in many clinical stroke trials during the past 20 years. Large phase III clinical trials of several classes of neuroprotectants (mainly NMDA receptor antagonists, free radical scavengers, and calcium channel blockers) have recently failed to demonstrate efficacy of neuroprotection. After initial disappointment, the active research continues and some new exciting neuroprotective models emerge on the horizon.Učinkovito liječenje akutnog moždanog udara velik je izazov u suvremenoj medicini. Terapijska neurozaštita kojom bi se ishemijsko neuronsko oštećenje u tkivu penumbre u područjima smanjenog moždanog krvnog protoka svelo na najmanju moguću mjeru čini se primamljivom zamisli u liječenju akutnog moždanog udara i moždane traume. ‘Ishemijska kaskada’, odnosno složen mehanizam metaboličnih događaja što ih potiče moždana ishemija, nudi mnoštvo putanja kojima bi neurozaštitna sredstva mogla djelovati. Vrijeme proteklo do početka liječenja ostaje glavnim ograničavajućim čimbenikom za mnoga potencijalna neurozaštitna sredstva. Iako točan terapijski prozor nije poznat, rezultati dobiveni u mnogobrojnim životinjskim modelima i kliničkim istraživanjima ukazuju na to da bi neurozaštitna terapija mogla biti učinkovita samo ako se dade vrlo rano nakon nastupa ishemije. Tijekom posljednjih 20 godina različita neurozaštitna sredstva ispitivana su u moždanom udaru u mnogim kliničkim pokusima. Nedavno provedeni veliki klinički pokusi III. faze s nekoliko skupina neurozaštitnih sredstava (uglavnom antagonista NMDA receptora, čistača slobodnih radikala i blokatora kalcijevih kanala) nisu dokazali učinkovitost neurozaštite. Nakon prvotnog razočaranja djelatna se istraživanja nastavljaju, a na obzoru se naziru neki novi i uzbudljivi modeli neurozaštite

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Previous data showed that PFOs not detected by high-quality transthoracic echocardiography are smaller and associated with small right-to-left shunts (4); therefore, they are far less likely to be associated with embolic stroke features (5)

Construct Validity of Cognitive Reserve in a Multiethnic Cohort: The Northern Manhattan Study

Cognitive reserve is a hypothetical construct that has been used to inform models of cognitive aging and is presumed to be indicative of life experiences that may mitigate the effects of brain pathology. The purpose of this study was to evaluate the construct validity of cognitive reserve by examining both its convergent and its discriminant validity across three different samples of participants using structural equation modeling. The cognitive reserve variables were found to correlate highly with one another (thereby providing evidence of convergent validity), but demanding tests of discriminant validity indicated that, in two of the samples, the cognitive reserve construct was highly related to an executive functioning construct

Predicting long-term outcome after acute ischemic stroke: a simple index works in patients from controlled clinical trials

Background and Purpose—An early and reliable prognosis for recovery in stroke patients is important for initiation of individual treatment and for informing patients and relatives. We recently developed and validated models for predicting survival and functional independence within 3 months after acute stroke, based on age and the National Institutes of Health Stroke Scale score assessed within 6 hours after stroke. Herein we demonstrate the applicability of our models in an independent sample of patients from controlled clinical trials. Methods—The prognostic models were used to predict survival and functional recovery in 5419 patients from the Virtual International Stroke Trials Archive (VISTA). Furthermore, we tried to improve the accuracy by adapting intercepts and estimating new model parameters. Results—The original models were able to correctly classify 70.4% (survival) and 72.9% (functional recovery) of patients. Because the prediction was slightly pessimistic for patients in the controlled trials, adapting the intercept improved the accuracy to 74.8% (survival) and 74.0% (functional recovery). Novel estimation of parameters, however, yielded no relevant further improvement. Conclusions—For acute ischemic stroke patients included in controlled trials, our easy-to-apply prognostic models based on age and National Institutes of Health Stroke Scale score correctly predicted survival and functional recovery after 3 months. Furthermore, a simple adaptation helps to adjust for a different prognosis and is recommended if a large data set is available. (Stroke. 2008;39:000-000.

Socioeconomic Status, Psychosocial Factors, Race and Nocturnal Blood Pressure Dipping in a Hispanic Cohort

BACKGROUND Little information is available about the relationship of socioeconomic status (SES) to blunted nocturnal ambulatory blood pressure (ABP) dipping among Hispanics and whether this relationship differs by race. We sought to characterize ABP nondipping and its determinants in a sample of Hispanics. METHODS We enrolled 180 Hispanic participants not on antihypertensive medications. SES was defined by years of educational attainment. All participants underwent 24-hour ABP monitoring. A decrease of <10% in the ratio between average awake and average asleep systolic BP was considered nondipping. RESULTS The mean age of the cohort was 67.1 ± 8.7, mean educational level was 9.4 ± 4.4 years, and 58.9% of the cohort was female. The cohort was comprised of 78.3% Caribbean Hispanics with the rest from Mexico and Central/South America; 41.4% self-identified as white Hispanic, 34.4% self-identified as black Hispanic, and 24.4% did not racially self- identify. The percentage of nondippers was 57.8%. Educational attainment (10.5 years vs. 8.6 years; P <0.01) was significantly higher among dippers than nondippers. In multivariable analyses, each 1-year increase in education was associated with a 9% reduction in the likelihood of being a nondipper (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84–0.98; P = 0.01). There were significantly greater odds of being a nondipper for black Hispanics than for white Hispanics (OR, 2.83, 95% CI, 1.29–6.23; P = 0.005). Higher SES was significantly protective of nondipping in white Hispanics but not black Hispanics. CONCLUSIONS These results document a substantial prevalence of nondipping in a cohort of predominantly normotensive Hispanics. Dipping status varied significantly by race. Lower SES is significantly associated with nondipping status, and race potentially impacts on this relation

Physical inactivity is a strong risk factor for stroke in the oldest old: Findings from a multi-ethnic population (the Northern Manhattan Study)

Background The fastest growing segment of the population is those age ≥80 who have the highest stroke incidence. Risk factor management is complicated by polypharmacy-related adverse events. Aims To characterize the impact of physical inactivity for stroke by age in a multi-ethnic prospective cohort study (NOMAS, n = 3298). Methods Leisure time physical activity was assessed by a validated questionnaire and our primary exposure was physical inactivity (PI). Participants were followed annually for incident stroke. We fit Cox-proportional hazard models to calculate hazard ratios and 95% confidence intervals (HR 95% CI) for the association of PI and other risk factors with risk of stroke including two-way interaction terms between the primary exposures and age (<80 vs. ≥80). Results The mean age was 69 ± 10.3 years and 562 (17%) were ≥80 at enrolment. PI was common in the cohort (40.8%). Over a median of 14 years, we found 391 strokes. We found a significant interaction of age ≥80 on the risk of stroke with PI (p = 0.03). In stratified models, PI versus any activity (adjusted HR 1.60, 95%CI 1.05–2.42) was associated with an increased risk of stroke among those ≥80. Conclusion Physical inactivity is a treatable risk factor for stroke among those older than age 80. Improving activity may reduce the risk of stroke in this segment of the population