Background: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. Objective: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. Methods: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. Results: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle– and high-income settings. Conclusions: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle–income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.
The incidence of neonatal stroke is high and currently there are no strategies to protect the neonatal brain from stroke or reduce the sequelae. Agents capable of modifying inflammatory processes hold promise. We set out to determine whether delayed administration of one such agent, minocycline, protects the immature brain in a model of transient middle cerebral artery (MCA) occlusion in 7-day-old rat pups. Injury volume in minocycline (45 mg/kg/dose, beginning at 2 h after MCA occlusion) and vehicle-treated pups was determined 24 h and 7 days after onset of reperfusion. Accumulation of activated microglia/macrophages, phosphorylation of mitogen-activated protein kinase (MAPK) p38 in the brain, and concentrations of inflammatory mediators in plasma and brain were determined at 24 h. Minocycline significantly reduced the volume of injury at 24 h but not 7 days after transient MCA occlusion. The beneficial effect of minocycline acutely after reperfusion was not associated with changed ED1 phenotype, nor was the pattern of MAPK p38 phosphorylation altered. Minocycline reduced accumulation of IL-1beta and CINC-1 in the systemic circulation but failed to affect the increased levels of IL-1beta, IL-18, MCP-1 or CINC-1 in the injured brain tissue. Therefore, minocycline provides early but transient protection, which is largely independent of microglial activation or activation of the MAPK p38 pathway.
Background and Purpose Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported five-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. Methods The Vascular effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009–2014, and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of stroke etiologies, including arteriopathies. Other predictors were measured via parental interview or chart review. Results Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0–3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% CI 4.6–10%) at one month and 12% (8.5–15%) at one year. The sole predictor of recurrence was presence of an arteriopathy, which increased the risk of recurrence 5-fold compared to an idiopathic AIS (hazard ration 5.0, 95% CI 1.8–14). The one-year recurrence rate was 32% (95% CI 18–51%) for moyamoya, 25% (12–48%) for transient cerebral arteriopathy, and 19% (8.5–40%) for arterial dissection. Conclusions Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.
Background and Purpose-Different strategies for neuroprotection of neonatal stroke may be required because the developing brain responds differently to hypoxia-ischemia than the mature brain. This study was designed to determine the role of caspase-dependent injury in the pathophysiology of pure focal cerebral ischemia in the immature brain. Methods-Postnatal day 7 rats were subjected to permanent or transient middle cerebral artery (MCA) occlusion.Diffusion-weighted MRI was used during occlusion to noninvasively map the evolving ischemic core. The time course of caspase-3 activation in ischemic brain tissue was determined with the use of an Asp-Glu-Val-Asp-aminomethylcoumarin cleavage assay. The anatomy of caspase-3 activation in the ischemic core and penumbra was mapped immunohistochemically with an anti-activated caspase-3 antibody in coronal sections that matched the imaging planes on diffusion-weighted MRI. Results-A marked increase in caspase-3 activity occurred within 24 hours of reperfusion after transient MCA occlusion.In contrast, caspase-3 activity remained significantly lower within 24 hours of permanent MCA occlusion. Cells with activated caspase-3 were prominent in the penumbra beginning at 3 hours after reperfusion, while a more delayed but marked caspase-3 activation was observed in the ischemic core by 24 hours after reperfusion. Conclusions-In the neonate, caspase-3 activation is likely to contribute substantially to cell death not only in the penumbra but also in the core after ischemia with reperfusion. Furthermore, persistent perfusion deficits result in less caspase-3 activation and appear to favor caspase-independent injury.
Background and aim: Effective implementation of early treatment strategies for stroke requires prompt admission to hospital. There are several reasons for delayed admission. Good awareness should facilitate early admission. We identified local targets for education. Methods: Four groups, each of 40 people, completed questionnaires to determine their knowledge of stroke symptoms and risk factors, and the action they took or would take in the event of a stroke. The groups were: patients with a diagnosis of stroke or TIA (within 48 hrs of admission); patients at risk of stroke; the general population; and nurses. Results: Forty per cent of stroke patients identified their stroke. Median time from onset of symptoms to seeking medical help was 30 minutes. Medical help was sought by the patient themselves in only 15% of cases. In 80% of cases the GP was called rather than an ambulance. Of the at risk group, 93% were able to list at least one symptom of acute stroke, as were 88% of the general population. An ambulance would be called by 73% of the at risk group in the event of a stroke. Patients with self reported risk factors for stroke were largely unaware of their increased risk. Only 7.5% of at risk patients acquired their stroke information from the medical profession. Conclusions: Public knowledge about stroke is good. However, stroke patients access acute services poorly. At risk patients have limited awareness of their increased risk. A campaign should target people at risk, reinforcing the diagnosis of stroke and access to medical services. E arly admission to hospital is critical for the effective implementation of early treatment strategies for stroke, 1 2 which have been shown to reduce morbidity and cost associated with the condition.3 4 Nevertheless, there is often a significant delay in patients with stroke reaching hospital.  This delay has three components: 9 appraisal delay, the time from noticing a symptom to deciding one is ill; illness delay, the time from onset of symptoms to seeking professional help; and utilisation delay, the time from seeking professional care to arrival at the hospital.Several public education campaigns have successfully increased the level of stroke knowledge.9 10 While it is assumed that good stroke knowledge results in faster access to medical services, this link has not been proven. 9 11-14 This study had two aims. Firstly, we identified factors governing delay in admission to hospital that could be the focus for education. Secondly, we determined education opportunities that are currently being missed. This study focused on less disabled patients, as patients with severe strokes are admitted sooner than those who are less disabled. 15 METHODSThe study was undertaken at Derriford Hospital in Plymouth, England. Four groups were studied: N Patients with a diagnosis of stroke or transient ischaemic attack (TIA), admitted during the previous 48 hours. Exclusion criteria were inability to communicate, impaired consciousness, or a diagnosis of subarachnoid haemor...
Objective Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS‐CoV‐2 is unknown. This study aimed to determine the proportion of pediatric SARS‐CoV‐2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS‐CoV‐2 in the first 3 months of the pandemic in an international cohort. Methods We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS‐CoV‐2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS‐CoV‐2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS‐CoV‐2 from March 1 to May 31, 2020. Results Of 42 centers with SARS‐CoV‐2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS‐CoV‐2 had ischemic strokes. Proportions of stroke cases positive for SARS‐CoV‐2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS‐CoV‐2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS‐CoV‐2. Seven of 8 patients with SARS‐CoV‐2 had additional established stroke risk factors. Interpretation As in adults, pediatric stroke is an infrequent complication of SARS‐CoV‐2, and SARS‐CoV‐2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS‐CoV‐2 in pediatric stroke better, SARS‐CoV‐2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657–665
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
334 Leonard St
Brooklyn, NY 11211
Copyright © 2023 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.