Cryptogenic Stroke Saver, Jeffrey L
The New England journal of medicine,
05/2016, Letnik:
374, Številka:
21
Journal Article
Recenzirano
One quarter of ischemic strokes are cryptogenic (no obvious cause). Additional investigation involves assessment for arteriopathies, cardiac sources of embolism (in particular, occult low-burden ...atrial fibrillation), and disturbances of coagulation.
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.
Stage
After a gym workout, a 48-year-old man had sudden ataxia, nausea, and diplopia, followed by persistent inability to see the upper left quadrant of space with either the left or right eye. He did not have neck pain. His medical history included hypertension and migraines with aura. Magnetic resonance imaging (MRI) showed a right occipitotemporal and thalamic infarct. Magnetic resonance angiography showed an abrupt cutoff of a distal segment of the right posterior cerebral artery. The complete blood count, prothrombin time, and partial-thromboplastin time were normal. Transthoracic echocardiographic results suggested a possible right-to-left shunt. Cardiac telemetry during the first . . .
For several years, the only therapy with proven efficacy for acute ischaemic stroke was alteplase, which is approved for use within 4·5 h after stroke onset in many countries, but only within 3 h in ...the USA. However, the recanalisation rate with alteplase is modest. Several trials have shown substantial clinical benefit of neurothrombectomy within 6 h of ischaemic stroke onset, which has initiated a new era of acute stroke therapy. As neurothrombectomy becomes part of standard practice, additional trials will be needed to determine the best way to organise delivery of this care. Continuing clinical trials with several types of advanced MRI and CT imaging to enhance patient selection are investigating alteplase, other thrombolytic drugs, and novel endovascular devices, for use in later time periods from stroke onset. Consequently, the organisation and implementation of future clinical trials will need to adapt to what has been learned from the present generation of trials. The delivery of care to patients with acute stroke will also need to incorporate newly proven therapies, and much additional work is needed to maximise outcomes in as many patients as possible.
Since large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit ...stroke-related dependence and death.
To delineate LVO-AIS impact, systematic search identified studies measuring dependence or death modified Rankin Scale (mRS) 3-6 or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset.
Among 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3-6) within 3-6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53-5.63,
< 0.0001). Mortality within 3-6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5-6.68),
< 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8-55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8-81.3%) of poststroke dependence or death and 95.6% (CI: 89.0-98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality.
LVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes.
Time is brain-quantified SAVER, Jeffrey L
Stroke,
2006, 2006-Jan, 2006-01-00, 20060101, Letnik:
37, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The phrase "time is brain" emphasizes that human nervous tissue is rapidly lost as stroke progresses and emergent evaluation and therapy are required. Recent advances in quantitative neurostereology ...and stroke neuroimaging permit calculation of just how much brain is lost per unit time in acute ischemic stroke.
Systematic literature-review identified consensus estimates of number of neurons, synapses, and myelinated fibers in the human forebrain; volume of large vessel, supratentorial ischemic stroke; and interval from onset to completion of large vessel, supratentorial ischemic stroke.
The typical final volume of large vessel, supratentorial ischemic stroke is 54 mL (varied in sensitivity analysis from 19 to 100 mL). The average duration of nonlacunar stroke evolution is 10 hours (range 6 to 18 hours), and the average number of neurons in the human forebrain is 22 billion. In patients experiencing a typical large vessel acute ischemic stroke, 120 million neurons, 830 billion synapses, and 714 km (447 miles) of myelinated fibers are lost each hour. In each minute, 1.9 million neurons, 14 billion synapses, and 12 km (7.5 miles) of myelinated fibers are destroyed. Compared with the normal rate of neuron loss in brain aging, the ischemic brain ages 3.6 years each hour without treatment. Altering single input variables in sensitivity analyses modestly affected the estimated point values but not order of magnitude.
Quantitative estimates of the pace of neural circuitry loss in human ischemic stroke emphasize the time urgency of stroke care. The typical patient loses 1.9 million neurons each minute in which stroke is untreated.
Patients who had had a cryptogenic stroke and had a PFO were randomly assigned to medical therapy or PFO closure. At a median of 5.9 years, the rate of recurrent ischemic strokes was lower in the PFO ...closure group than in the medical-therapy group.
IMPORTANCE: Comparative assessment of acute ischemic stroke care quality provided by hospitals in the United States has been hampered by the unavailability of the National Institutes of Health Stroke ...Scale (NIHSS) in administrative data sets, preventing adequate adjustment for variations in patient case-mix risk. In response to stakeholder concerns, the US Centers for Medicare & Medicaid Services in 2016 implemented optional reporting of NIHSS scores. OBJECTIVE: To analyze the distributional, convergent, and predictive validity of nationally submitted NIHSS values in the National Inpatient Sample. DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cross-sectional study took place from October 1 to December 31, 2016. The nationally representative sample included US adults who had ischemic stroke hospitalizations during the first calendar quarter in which optional NIHSS reporting was implemented. Analysis began September 2019. MAIN OUTCOMES AND MEASURES: Distribution of NIHSS scores, functional independence at discharge, inpatient mortality, and administrative reporting of NIHSS. RESULTS: Among 154 165 ischemic stroke hospitalizations during the first 3 months of the reporting policy, NIHSS scores were reported in 21 685 patients (14%) (10 925 women 50.4%; median interquartile range age, 72 61-82 years). Median (interquartile range) NIHSS score was 4 (2-11), and frequency of severity categories included absent (NIHSS score, 0) in 2080 patients (9.6%), minor (NIHSS score, 1-4) in 8760 patients (40.4%), and severe (NIHSS score, 21-42) in 1930 patients (8.9%). National Institutes of Health Stroke Scale score of 10 or more, an indicator of possible large vessel occlusions, was present in 6290 patients (29%). Presenting NIHSS score was higher in very elderly patients (age ≥80 y) and women and also in patients receiving endovascular thrombectomy vs intravenous thrombolysis alone vs no reperfusion therapy (median interquartile range, 17 12-22 vs 6 4-12 vs 4 2-9, respectively) (P < .001). National Institutes of Health Stroke Scale scores were similarly higher for discharge outcomes of mortality vs discharge to skilled nursing facility vs discharge home (median interquartile range, 19 12-25 vs 7 3-15 vs 2 1-5, respectively) (P < .001). Likelihood of NIHSS scores being reported independently increased with interfacility transfer, receipt of acute reperfusion therapies, larger hospital size, academic centers, and region other than the West. CONCLUSIONS AND RELEVANCE: In the initial national optional reporting period in the United States, NIHSS scores were reported in nearly 1 in 7 ischemic stroke hospitalizations. The distribution of NIHSS scores was similar to that from narrow population-based studies and registries, and NIHSS scores were powerfully associated with discharge outcome, supporting the validity and potential to aid care quality assessment.
BACKGROUND AND PURPOSE—TNK (tenecteplase), a newer fibrinolytic agent, has practical delivery advantages over ALT (alteplase) that would make it a useful agent if noninferior in acute ischemic stroke ...treatment outcome. Accordingly, the most recent US American Heart Association/American Stroke Association acute ischemic stroke guideline recognized TNK as an alternative to ALT, but only based on informal consideration, rather than formal meta-analysis, of completed randomized control trials.
METHODS—Systematic literature search and formal meta-analysis were conducted per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses), adapted to noninferiority analysis. The primary outcome of freedom from disability (modified Rankin Scale score, 0–1) outcome at 3 m, and additional efficacy and safety outcomes, were analyzed.
RESULTS—Systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% male, baseline National Institutes of Health Stroke Scale mean 7.0, and time from last known well to treatment start mean 148 minutes. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary end point, crude cumulative rates of disability-free (modified Rankin Scale score, 0–1) 3 m outcome were TNK 57.9% versus ALT 55.4%. Informal, random-effects meta-analysis, the risk difference was 4% (95% CI, −1% to 8%). The lower 95% CI bound fell well within the prespecified noninferiority margin. Similar results were seen for the additional efficacy end pointsfunctional independence (modified Rankin Scale score, 0–2)crude TNK 71.9% versus ALT 70.5%, risk difference 2% (95% CI, −3% to 6%); and modified Rankin Scale shift analysis, common odds ratio 1.21 (95% CI, 0.93–1.57). For safety end points, lower event rates reduced power, but point estimates were also consistent with noninferiority
CONCLUSIONS—Accumulated clinical trial data provides strong evidence that TNK is noninferior to ALT in the treatment of acute ischemic stroke. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.
Stroke recently declined from the third to the fourth leading cause of death in the United States, its first rank transition among sources of American mortality in nearly 75 years.
This is a ...narrative review supplemented by new analyses of Centers for Disease Control and Prevention National Vital Statistics Reports from 1931 to 2008.
Historically, stroke transitioned from the second to the third leading cause of death in the United States in 1937, but stroke death rates were essentially stable from 1930 to 1960. Then a long, great decline began, moderate in the 1960s, precipitous in the 1970s and 1980s, and moderate again in the 1990s and 2000s. By 2008, age-adjusted annual death rates from stroke were three fourths less than the historic 1931 to 1960 norm (40.6 versus 175.0 per 100,000). Total actual stroke deaths in the United States declined from a high of 214,000 in 1973 to 134,000 in 2008. Improved stroke prevention, through control of hypertension, hyperlipidemia, and tobacco, contributed most greatly to the mortality decline with a lesser but still substantial contribution of improved acute stroke care. Persisting challenges include race-ethnicity, sex, and geographic disparities in stroke mortality; the burden of stroke disability; the expanding obesity epidemic and aging of the US population; and the epidemic of cerebrovascular disease in low- and middle-income countries worldwide.
The recent rank decline of stroke among leading causes of American death is testament to a half century of societal progress in cerebrovascular disease prevention and acute care. Renewed commitments are needed to preserve and broaden this historic achievement.
BACKGROUND: Statin agents play a major role in secondary prevention after acute cerebral ischemia (ACI) events but are not indicated in all patients with ischemic stroke and transient ischemic ...attack. National guidelines recommend statins for patients with ACI of large or small vessel atherosclerotic origin and without these stroke mechanisms but coexisting coronary artery disease or primary prevention indications. The potential adverse effect burden of statin overuse in the remaining ACI patients have not been well delineated. METHODS: Per Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines, we performed systematic meta-analyses of: (1) statin randomized clinical trials to determine absolute risk increases for 6 major adverse events; (2) large clinical series to determine the proportion of ACI events due to large or small vessel atherosclerotic disease; and (3) the proportion of remaining patients with coronary artery disease/primary prevention statin indications. RESULTS: For adverse effects, data were available from 63 randomized clinical trials enrolling 155 107 patients. Statin therapy was associated with an increased risk of the occurrence of 6 conditions: diabetes, myalgia or muscle weakness, myopathy, liver disease, renal insufficiency, and eye disease. Across 55 large series enrolling 53 501 patients, the rate of ACI due to large and small artery atherosclerosis was 45.0% (large artery atherosclerosis 21.6%, small vessel disease 23.4%), the rate of remaining patients with coronary artery disease/primary prevention statin indications was 31.8%, and the rate of patients without statin indications was 23.2%. Data synthesis indicated that, in the United States, were all patients with ACI without statin indications treated with statins, a total of 5601 patients would develop needless adverse events each year, most commonly diabetes, myopathy, and eye disease. CONCLUSIONS: More than one-fifth of patients with ACI do not have an indication for statins, and statin overuse in these patients could annually lead to over 5600 adverse events each year in the United States, including diabetes, myopathy, and eye disease. These findings emphasize the importance of adhering to guideline indications for the start of statin therapy in ACI.
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