Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis causes cerebral dysfunction in the short and long term and induces disruption of the ...blood-brain barrier (BBB), neuroinflammation, hypoperfusion, and accumulation of amyloid β (Aβ) and tau protein in the brain. White matter changes and brain atrophy can be detected using brain imaging, but unfortunately, there is no specific treatment that directly addresses the underlying mechanisms of cognitive impairments in sepsis. Here, we review the underlying mechanisms of sepsis-associated brain injury, with a focus on BBB dysfunction and Aβ and tau protein accumulation in the brain. We also describe the neurological manifestations and imaging findings of sepsis-associated brain injury, and finally, we propose potential therapeutic strategies for acute and long-term cognitive impairments associated with sepsis. In the acute phase of sepsis, we suggest using antibiotics (such as rifampicin), targeting proinflammatory cytokines, and preventing ischemic injuries and hypoperfusion. In the late phase of sepsis, we suggest targeting neuroinflammation, BBB dysfunction, Aβ and tau protein phosphorylation, glycogen synthase kinase-3 beta (GSK3β), and the receptor for advanced glycation end products (RAGE). These proposed strategies are meant to bring new mechanism-based directions for future basic and clinical research aimed at preventing or ameliorating acute and long-term cognitive impairments in patients with sepsis.
Medical complications after stroke Kumar, Sandeep, MD; Selim, Magdy H, MD; Caplan, Louis R, MD
Lancet neurology,
2010, 2010-Jan, 2010-01-00, 20100101, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Summary Patients who have had a stroke are susceptible to many complications. These individuals commonly have comorbidities such as hypertension, diabetes, heart disease, or other ailments that ...increase the risks of systemic medical complications during stroke recovery. However, several complications can arise as a direct consequence of the brain injury itself, from the ensuing disabilities or immobility, or from stroke-related treatments. These events have a substantial effect on the final outcome of patients with stroke and often impede neurological recovery. Cardiac complications, pneumonias, venous thromboembolism, fever, pain, dysphagia, incontinence, and depression are particularly common after a stroke and usually require specific interventions for their prevention and treatment. However, there are few data to guide the management of these complications. Systematic investigations are therefore needed to further study the effects of medical complications on stroke recovery and to improve interventions for the prevention and treatment of these events.
PURPOSE—The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage.
METHODS—A formal literature search ...of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee.
RESULTS—Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated.
CONCLUSIONS—Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted. These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage.
IMPORTANCE: Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of ...endovascular intervention among subgroups needs better definition. OBJECTIVE: To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES: We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION: Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS: Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES: Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS: Data were included from 8 trials involving 2423 patients (mean SD age, 67.4 14.4 years; 1131 46.7% women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14–2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events 5.7% vs 53 events 5.1%; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths 15.8% vs 201 deaths 17.8%; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.
IMPORTANCE: Intracerebral hemorrhage (ICH) has the highest mortality of all stroke types and is the most serious complication of anticoagulation. Data regarding trends in ICH incidence and ...location-specific risk factors on the population level are conflicting. OBJECTIVE: To assess long-term population-based trends in the incidence of ICH, examine incidence rates stratified by deep and lobar locations, and characterize location-specific risk factors. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal prospective community-based cohort study comprised 10 333 original participants (n = 5209; age range, 28-62 years) and offspring participants (n = 5124; age range, 5-70 years) from the Framingham Heart Study who were followed up from January 1, 1948, to December 31, 2016. Original and offspring patient cohorts were confirmed to have experienced a spontaneous ICH event through imaging or pathologic testing. A total of 129 participants were identified with a primary incident of ICH. After exclusions, the remaining 99 patients were divided into 2 nested case-control samples, which were created by stratifying the first incident of ICH by brain region (lobar ICH or deep ICH), with 55 patients included in the lobar ICH sample and 44 patients included in the deep ICH sample. Patients were matched by age and sex (1:4 ratio) with 396 individuals without any stroke event (the control group). No participant in the patient samples was excluded or approached for consent, as their initial consent to participate in the Framingham Heart Study included consent to follow-up of cardiovascular outcomes. Data were analyzed in October 2019. MAIN OUTCOMES AND MEASURES: The unadjusted and age-adjusted ICH incidence rates, assessed in 3 periods (period 1, from 1948-1986; period 2, from 1987-1999; and period 3, from 2000-2016) to study incidence trends. Nested case-control samples were used to examine baseline risk factors and medication exposures with the incidence of ICH events located in the lobar and deep brain regions within the 10 years before participants experienced a stroke event. RESULTS: Of 10 333 original and offspring participants in the Framingham Heart Study, 129 patients (72 women 55.8%; mean SD age, 77 11 years) experienced a primary ICH incident during a follow-up period of 68 years (301 282 person-years), with an incidence rate of 43 cases per 100 000 person-years. The unadjusted incidence rate increased over time, but the age-adjusted incidence rate decreased slightly between periods 2 and 3. An age-stratified analysis indicated a continued increase in ICH incidence among patients 75 years and older, reaching 176 cases per 100 000 person-years in period 3. A concurrent 3-fold increase in the use of anticoagulant medications was observed, from 4.4% in period 2 to 13.9% in period 3. The incidence rate increased substantially with age for both lobar and deep ICH. Higher systolic and diastolic blood pressure and statin medication use (odds ratio OR, 4.07; 95% CI, 1.16-14.21; P = .03) were associated with the incidence of deep ICH. Higher systolic blood pressure and apolipoprotein E ε4 allele homozygosity (OR, 3.66; 95% CI, 1.28-10.43; P = .02) were associated with the incidence of lobar ICH. CONCLUSIONS AND RELEVANCE: This study found that the incidence of ICH increased in the oldest patients. Hypertension is a treatable risk factor for both deep and lobar ICH, while the use of statin medications is associated with the risk of a deep ICH event.
Perihaematomal oedema (PHO) is an important pathophysiological marker of secondary injury in intracerebral haemorrhage (ICH). In this Review, we describe a novel method to conceptualize PHO formation ...within the framework of Starling's principle of movement of fluid across a capillary wall. We consider progression of PHO through three stages, characterized by ionic oedema (stage 1) and progressive vasogenic oedema (stages 2 and 3). In this context, possible modifiers of PHO volume and their value in identifying patients who would benefit from therapies that target secondary injury are discussed; the practicalities of using neuroimaging to measure PHO volume are also considered. We examine whether PHO can be used as a predictor of neurological outcome following ICH, and we provide an overview of emerging therapies. Our discussion emphasizes that PHO has clinical relevance both as a therapeutic target, owing to its augmentation of the mass effect of a haemorrhage, and as a surrogate marker for novel interventions that target secondary injury.
OBJECTIVE:To examine the association between enlarged perivascular spaces (EPVS) and the prevalence and extent of small acute diffusion-weighted imaging (DWI) lesions (SA-DWIL) in patients with ...spontaneous supratentorial intracerebral hemorrhage (ICH).
METHODS:We conducted a retrospective review of a consecutive cohort of 201 patients with spontaneous supratentorial ICH who had brain MRI with DWI within 1 month of ICH onset. We compared the clinical and imaging characteristics, including EPVS, of patients with and without SA-DWIL. We used univariate and multivariate logistic regression analyses to determine the variables associated with SA-DWIL.
RESULTS:Small acute DWI lesions were detected in 27.9% (n = 56) of patients. Intraventricular and subarachnoid extension of ICH (p ≤ 0.001), high centrum semiovale (CSO)–EPVS (p < 0.001), high basal ganglia–EPVS (p = 0.007), overall extent of white matter hyperintensity (p = 0.018), initial ICH volume (p < 0.001), and mean change in mean arterial blood pressure (δ MAP = MAP at admission − the lowest MAP before MRI scan) (p = 0.027) were associated with SA-DWIL on univariate analyses. On multivariate logistic regression analyses, larger ICH volume (odds ratio OR 1.03; 95% confidence interval CI 1.01–1.06; p = 0.006) and high CSO-EPVS (OR 12.56; 95% CI 4.40–35.85; p < 0.001) were independently associated with the presence of SA-DWIL.
CONCLUSIONS:In our cohort, high EPVS, in particular CSO-EPVS, and larger hematoma volume emerged as independent predictors for SA-DWIL after ICH. Our findings might provide a new explanation for the pathophysiologic mechanisms predisposing to SA-DWIL after ICH.
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