Incidence Of Stroke In Children Research Articles

Factors Influencing Recovery From Pediatric Stroke Based on Discussions From a UK-Based Online Stroke Community: Qualitative Thematic Study.

The incidence of stroke in children is low, and pediatric stroke rehabilitation services are less developed than adult ones. Survivors of pediatric stroke have a long poststroke life expectancy and therefore have the potential to experience impairments from their stroke for many years. However, there are relatively few studies characterizing these impairments and what factors facilitate or counteract recovery. This study aims to characterize the main barriers to and facilitators of recovery from pediatric stroke. A secondary aim was to explore whether these factors last into adulthood, whether they change, or if new factors impacting recovery emerge in adulthood. We performed a qualitative thematic analysis based on posts from a population of participants from a UK-based online stroke community, active between 2004 and 2011. The analysis focused on users who talked about their experiences with pediatric stroke, as identified by a previous study. The posts were read by 3 authors, and factors influencing recovery from pediatric stroke were mapped into 4 areas: medical, physical, emotional, and social. Factors influencing recovery were divided into short-term and long-term factors. There were 425 posts relating to 52 survivors of pediatric stroke. Some survivors of stroke posted for themselves, while others were talked about by a third party (mostly parents; 31/35, 89% mothers). In total, 79% (41/52) of survivors of stroke were aged ≤18 years and 21% (11/52) were aged >18 years at the time of posting. Medical factors included comorbidities as a barrier to recovery. Medical interventions, such as speech and language therapy and physiotherapy, were also deemed useful. Exercise, particularly swimming, was deemed a facilitator. Among physical factors, fatigue and chronic pain could persist decades after a stroke, with both reported as a barrier to feeling fully recovered. Tiredness could worsen existing stroke-related impairments. Other long-standing impairments were memory loss, confusion, and dizziness. Among emotional factors, fear and uncertainty were short-term barriers, while positivity was a major facilitator in both short- and long-term recovery. Anxiety, grief, and behavioral problems hindered recovery. The social barriers were loneliness, exclusion, and hidden disabilities not being acknowledged by third parties. A good support network and third-party support facilitated recovery. Educational services were important in reintegrating survivors into society. Participants reported that worrying about losing financial support, such as disability allowances, and difficulties in obtaining travel insurance and driving licenses impacted recovery. The lived experience of survivors of pediatric stroke includes long-term hidden disabilities and barriers to rehabilitation. These are present in different settings, such as health care, schools, workplaces, and driving centers. Greater awareness of these issues by relevant professional groups may help ameliorate them.

A 13-Month-Old Iranian Boy with Thrombosis of the Left Transverse and Superior Sagittal Sinuses Due to Homozygous Mutations in MTHFR A1298C: A Case Report & Review of Literature

Background and Aims: Cerebral sinus venous thrombosis (CSVT) is a rare stroke subtype in children, with limited data on its clinical presentation, etiology, and outcomes. This case report aims to describe a case of CSVT in a child, including their clinical presentation, imaging findings, and management, to increase awareness of this rare but serious condition. Case presentation: A 13-month-old boy presented with swelling and deviation of the left eye after being hospitalized for left periorbital cellulitis. The patient was diagnosed with thrombosis of the left transverse and superior sagittal sinuses and underwent treatment with levetiracetam, folinic acid, rosuvastatin and enoxaparin followed by warfarin. Genetic testing was also performed to identify the underlying genetic basis of thrombophilia. Results: Laboratory tests showed that there was one heterozygous mutation in the β-Fibrinogen gene and three homozygous mutations in MTHFR A1298C, PAI-I-675 4G/5G, and PAI-I-844 G/A genes. Additionally, Lipoprotein (a) was measured at 89.3 nmol/L and the patient's mother had two homozygous mutations in PAI-I-675 4G/5G and PAI-I-844 G/A genes. Conclusions: It appears that the mutation in MTHFR gene is more prevalent in our region, which may be a contributing factor to the increased incidence of stroke in children and adolescents in the country. Further research is needed to determine the prevalence of this mutation and its impact on thrombophilia in the population. This case highlights the importance of prompt diagnosis and treatment of CSVT in children, as well as the need for genetic counselling and testing to identify underlying risk factors.

The incidence of pediatric ischemic stroke: A systematic review and meta-analysis.

Despite its importance in being among the top 10 causes of childhood death, there is limited data on the incidence of stroke in children and whether this has changed over time. We performed a systematic review and meta-analysis to estimate the worldwide incidence rate of pediatric ischemic stroke, identify population differences, and assess trends in incidence. We screened three databases (Medline, Embase, and Cumulative Index of Nursing and Allied Health Literature (CINAHL)) and a Google Search was performed up to October 2021. The protocol was pre-registered: PROSPERO: CRD42021273749. Data extraction and quality assessment were independently undertaken by two reviewers. A random-effects model was used for meta-analysis using Stata SE17 to calculate the overall incidence rate. Heterogeneity was assessed using I2. Meta-regression and assessment for bias were performed. Out of 4166 records identified, 39 studies were included in the qualitative synthesis and the quantitative meta-analysis. The incidence rate for all ischemic strokes varied from 0.9 to 7.9 per 100,000 person-years, with a pooled incidence of 2.09 (95% confidence interval (CI): 1.57-2.76). The pooled incidence was 1.28 (95% CI: 0.75-2.19) per 100,000 person-years for arterial ischemic stroke, and 0.56 (95% CI: 0.31-1.02) per 100,000 person-years for cerebral venous sinus thrombosis. The incidence of arterial ischemic stroke was high in neonates, less than 28 days old (18.51, 95% CI: 12.70-26.97). Significant heterogeneity was observed in the initial analyses of stroke incidence estimates, and geographical region, cohort age upper limit, length of study, study quality, and study design could not explain this. The incidence rate of childhood stroke appeared remained relatively stable over time. Our review provides estimates of global stroke incidence, including stroke subtypes, in children. It demonstrates a particularly high stroke incidence in neonates.

Low Stroke Risk in Children With Sickle Cell Disease in French Guiana: A Retrospective Cohort Study.

One in every 227 babies born in French Guiana has sickle cell disease, which represents the greatest incidence in France. This study aimed to determine the incidence of stroke in children with sickle cell disease and its associated risk factors. This retrospective cohort study included all children with sickle cell disease diagnosed in the neonatal period who were born in French Guiana between 01/01/1992 and 12/31/2002. Of a total of 218 records, 122 patients were included. There were 70 HbSS/Sβ0 (58%), 40 HbSC (33%), and 11 Sβ + thalassemia (9%). The number of emergency admissions was significantly different between genotypes, with a higher number in SS/Sβ0 children (p = 0.004). There were significantly more acute chest syndromes (p = 0.006) and more elevated Lactate Dehydrogenase in SS/Sβ0 patients (p = 0.003). Three of these patients had ischemic strokes at a mean age of 6.9 years, and one had a hemorrhagic stroke at the age of 9,2 years. The incidence rate of ischemic stroke for SS/Sβ0 children was 3.1 (95% CI: 1.0–9.7) per 1,000 patient-years, and the clinically apparent stroke risk by the age of 15 years and 3 months was 6,4%. The incidence of hemorrhagic stroke was 1.1 (95% CI: 0.1–7.4) per 1,000 patients-years. No patient with SC or Sβ + thalassemia genotypes experienced any stroke.

Study of transcranial Doppler ultrasound and endothelin-1 in children with sickle cell anemia: a single-center study

To assess the impact of our transcranial Doppler (TCD) screening program on the incidence of a first stroke in children with sickle cell anemia and to study the role of elevated serum endothelin-1 (an inflammatory mediator) in these children. Background: stroke is a major complication of sickle cell disease (SCD), even in very young children. About 11% of children with homozygous sickle cell anemia (SS) develop stroke by the end of the second decade of life. The underlying etiology in most cases is an ischemic stroke caused by large-vessel stenosis or occlusion. Transcranial Doppler (TCD) recommended as a routine screening test to identify children at high risk of developing a stroke, measures flow velocities within large intracranial arteries. TCD should be routinely performed in children between 2 and 16 years as this age group is at the highest risk of sickle cerebral vasculopathy. We carried out a prospective case-control study which included 2 groups: a patient group consisted of 30 children with sickle cell anemia and sickle thalassemia and a group of 30 healthy children of matched age and sex. Each group included 11 males (36.5%) and 19 females (63.5%); the age range was 2 to 17 years. Both groups underwent a thorough clinical examination and laboratory tests (CBC, liver and renal function, serum ferritin and endothelin-1). Additionally, TCD was performed in all children included in the patient group. According to the results of TCD, time-averaged mean of the maximum velocity (TAMMX) was < 170 cm/s (normal), 170–200 cm/s (conditional), ≥ 200 cm/s (high risk) in 20 (66.7%), 4 (13.3%) 6 (20%) patients, respectively. The level of endothelin-1 was significantly higher in the patients (57.1 ± 91.3) than in the controls (21.9 ± 14.8). Hemoglobin concentration was significantly lower in the patient group than in the control group, but the levels of reticulocytes, WBCs and serum ferritin were significantly higher in the patients than in the healthy controls. Serum Endotheline-1 level was higher in patients with sickle cell anemia than control group.

Ischemic stroke in children depending on risk factors

Background: Ischemic stroke (IS) in children is a major neuropediatric emergency. The incidence of stroke in children is from 2 to 13 for 100000 children. IS in perinatal period occurs in 1 for 2300 – 5000 live births. Material and methods: In 2010 – 2019 in the Republic of Moldova was carried out a retrospective as well as prospective study on a cohort of 458 children diagnosed with stroke. Were studied possible risk factors related to IS. Out of 458 children, 284 children with IS were selected and diagnosed during the reference period. Results: IS was determined in 284 cases with the diagnosis of stroke (62%, 95CI 59.73-64.27). Among the most common risk factors for the development of neonatal IS are pathologies of amniotic membranes in 113 cases (39.8%, 95CI 36.9-42.7), pathologies of amniotic fluid with meconium in 135 cases (47.5%, 95CI 44.54-50.46), and history of urgent caesarean section in 132 cases (46.5%, 95CI 43.54-49.46). Among the etiological causes of IS in the studied children were: congenital heart anomalies in 52 cases (18.3%, 95CI 16.01-20.59), neonatal encephalopathy in 27 cases (9.5%, 95CI 7.76-11.24), genetic syndromes in 18 cases (6.3%, 95CI 4.85-7.75), sickle cell disease – 5 (1.8%, 95CI 1.06–2.54), MELAS syndrome – 4 (1.4%, 95CI 0.7-2.1). Conclusions: IS risk factors are an important problem in clinical research. Most often, there is not a single risk factor responsible for the development of IS in children

Abstract P589: Pediatric Thrombectomy: Design And Workflow Lessons From Two Experienced Centers

Introduction: While clinical trials have demonstrated the remarkable efficacy of endovascular thrombectomy (EVT) for treating adult patients suffering from acute ischemic stroke (AIS), benefits reaped from advances in adult stroke care have unfortunately not occurred in parallel with pediatric stroke care. Randomized trials of EVT in childhood stroke are unlikely given the low incidence of stroke in children compared to adults, and despite promising outcomes in small case reports and series, EVT in children remains an off-label procedure lacking established consensus guidelines. Along with a clear need to collect prospective pediatric EVT outcome data, there is a need to enhance pediatric stroke care infrastructure to provide high-quality care to children experiencing stroke. Methods: In this work, we review two successful pediatric thrombectomy programs, examining key workflow design features that are likely to be important for other programs that aspire to implement pediatric EVT capability. Discussion: While pediatric EVT workflows will vary between centers, we identify several key elements of programmatic success shared between the two reviewed stroke programs that may serve as foundational design considerations for centers aiming to develop their own pediatric EVT programs. These elements include a formalized protocol and workflow, integration with an adult EVT workflow, simplification and automation of workflow steps, pediatric adaptations of stroke imaging, advocacy of pediatric stroke care, and collaboration between providers, among others. These essential features transcend any single hospital environment and may provide an important foundation for other pediatric centers that aim to enhance the care of children with stroke. Conclusion: EVT shows promise in reducing stroke-associated morbidity in children. To maximize the efficacy of this intervention, workflow optimizations discussed here should be implemented by centers seeking to develop local pediatric EVT capability.

Neurological events in children with infective endocarditis: Results from a prospective cohort

Despite all improvements in diagnostic imaging and therapeutic modalities, Infective endocarditis (IE) remains a highly letal disease especially in children. Stroke is an uncommon complication of endocarditis in children but it is an major cause of acquired brain injury and is assiociated with a higher mortality rate. To determine the prevalence of neurological events in infective endocarditis among children in the Tunisian context. This was a prospective study that enrolled all children admitted for IE in the cardiology department of Monastir hospital between 1983 and 2017. Included Patients had definite IE based on the modified Ducke criteria. Fourty children with IE were identified, including 19 boys and 21 girls aged one to eighteen years. Sixteen (40%) had congenital heart disease. Left-sided IE occurred in 33 patients (82.5%), and vegetations were identified in 33 individuals (82.5%). The most often encountered microorganisms in our population were Streptococcus viridans and Staphylococcus aureus, which were identified in five and four patients, respectively. Stroke occurred in 9 patients, including five with cerebral infarction and three with intracerebral hemorrhage. The incidence of stroke in children with left-sided IE was significantly higher than in those with right-sided IE (17.5% vs. 2.5%, P < 0.001). The most common manifestation of stroke was hemiparesis (63%). The mortality in children with IE was 50%. The mortality rate in patients who had stroke was significantly higher than those who hadn’t (75% versus 35%, P = 0.05). Our study indicates that stroke is common among children with IE, especially in those with left-sided IE, and stroke may increase their risk of death.

Neurological events in children's infective endocarditis: A prospective cohort

Despite all improvements in diagnostic imaging modalities and therapeutic regimens, Infective endocarditis remains a lethal disease especially in children. Stroke is an uncommon complication of endocarditis in children but it is an important cause of acquired brain injury which is associated with a higher mortality rate. This was a prospective study that included all children diagnosed with infective endocarditis (IE) and hospitalized in the cardiology department of Monastir hospital between 1983 and 2017. We included patients who were diagnosed with definite infective endocarditis based on the modified Ducke criteria. Forty children with infective endocarditis were identified, including 19 boys and 21 girls aged Twelve months to eighteen years sixteen (40%) of these individuals had congenital heart disease. Left-sided endocarditis occurred in 33 patients (82.5%), and vegetations were found in 33 individuals (82.5%). The most often encountered micro-organisms in our population were Streptococcus viridans and Staphylococcus aureus, which were identified in five and four patients, respectively. Postendocarditis stroke occurred in 9 patients, including five with cerebral infarction, three with intracerebral hemorrhage and one with pulmonary infraction. The incidence of stroke in children with left-sided endocarditis was significantly higher than those with right-sided endocarditis (17.5% versus 2.5%, P < 0.01). The most common manifestation of stroke was hemiparesis (63%). The mortality in children with endocarditis was important (50%). The mortality rate in patients who had stroke was significantly higher than those who had not (75% versus 35%, P < 0.05). Our study indicates that stroke is common among children with infective endocarditis, especially in those with left-sided endocarditis, and major stroke may increase their risk of death.

Incidence and Etiology of Stroke among Hospitalized Children: A Case-Series Study.

Stroke is a sudden blockage or rupture of brain vessels resulting neural defect or impairment. We aimed to investigate the incidence and causes of stroke in hospitalized children (Tehran-Iran, 2008-2013). This case series study was carried out in pediatric ward of tertiary care Vali-Asr Hospital, Imam Khomeini Hospitals Complex (Tehran- Iran) from 2008 to 2013. One month to 15 yr old admitted children due to stroke were enrolled into this case series study. Diagnosis was confirmed with brain imaging. Participants' demographic data, potential risk factors and neuroimaging findings were obtained from Hospital Reporting System. Recorded data were studied and considered regarding the incidence of stroke and its causes. Indeed we investigated cardiological causes as well as different items related to hematological disorders. Of 20000 admitted subjects in Imam Hospital during 5 yr, stroke was diagnosed in 15 cases. The incidence among the population study was 0.75 per 100000 children. Stroke was more frequent in males than females ( ). The most common age of stroke was 4-6 yr and the mean age of stroke was 58.8 months equal to 4.9 year. The most frequent stroke was hemorrhagic stroke (26%), followed by vascular (20%) and coagulopathy disorders (20%). The incidence of stroke in children was 0.75 per 100000. Hemorrhagic stroke due to major trauma, coagulopathy and vasculopathy were observed as most frequent causes that necessitate implementing some strategies for prevention, earlier diagnosis, and treatment.

Pediatric Infective Endocarditis and Stroke: A 13-Year Single-Center Review

ObjectiveWe explored the relationship between pediatric infective endocarditis and stroke. Patients and MethodsAll children encountered with infective endocarditis from January 2002 to December 2015 were included as our sample, and their medical records were comprehensively reviewed. ResultsSixty children with infective endocarditis were identified, including 30 boys and 30 girls aged eight months to 18 years (mean ± SD: 10.3 ± 5.6), and om 43 (71.6%) of these individuals had congenital heart disease. Left-sided endocarditis occurred in 25 patients (41.7%), and vegetations were found in 58 individuals (96.6%). The most often encountered microorganisms were Streptococcus viridans and Staphylococcus aureus, which were identified in five and four patients, respectively. Postendocarditis stroke occurred in nine patients, including five with cerebral infarction, two with intracerebral hemorrhage, and one with subarachnoid hemorrhage. The remaining child experienced cerebral infarction, intracerebral hemorrhage and subarachnoid hemorrhage simultaneously. The incidence of stroke in children with left-sided endocarditis was significantly higher than that of which in those who had right-sided endocarditis (32% versus 2.8%, P < 0.01). The most common manifestation of stroke was hemiparesis (55.5%). Two girls died of stroke, and the mortality rate in the patients who had stroke was significantly higher than that in those without stroke (22.2 % versus 3.9 %, P < 0.05). ConclusionsOur data indicate that stroke is common among children with infective endocarditis, especially in those with left-sided endocarditis, and major stroke may increase their risk of death. Congenital heart disease is the main underlying disease in children with infective endocarditis in China.

Clinico-epidemiological study of childhood stroke in Children Welfare Teaching Hospital/Baghdad

Background: The annual incidence of stroke in children after the newborn period is approximately 2.3 per 100000. Half are ischemic, and half are non-traumaticintracerebral and subarchnoidal hemorrhages.Objectives: To study the etiologic factors, clinical presentation andoutcome of stroke among children admitted to children welfare teaching hospital/Baghdad.Patient and methods: A prospective study was carried out in Children Welfare Teaching Hospital;Children age ranged between 1 month -13 years and was admitted to pediatric neurology ward between 1st of November 2013 and 1st of November 2014. After carful clinical history, physical and neurological examinations, the diagnosis of brain stroke was confirmed in all patients by computerized tomography (CT) and/or magnetic resonance imaging (MRI). Patients included in this study were those diagnosed as having ischemic stroke, hemorrhagic stroke.Results: The total number of cases were 61, 36 were male (59%). The age at onset ranged from 1-156 months. Ischemic stroke constituted 39 patients (63.9%). The most common etiologic factors for the ischemic stroke were protein C deficiency (9, 23.1%). The most common etiologic factor for hemorrhage was bleeding disorders in about 50% of patients. The most common presenting features were hemiplegia, seizure, alteration of consciousness; Cranial nerves palsy is mostly present in the ischemic stroke (14,35.9%) and only in one patient (4.5%) of hemorrhagic stroke.Conclusions: Ischemic stroke is more common than hemorrhagic stroke in pediatric age group. The significant risk factors for ischemic stroke are protein C deficiency, Congenital heart disease(CHD) and positive family history, while vitamin K deficiency, prolong Partial thromboplastin time (PTT) and trauma are significant for hemorrhagic stroke. The most common clinical features of both types of stroke are hemiparesis, siezure and alteration of consciousness.

الاسباب والانماط السريرية للجلطة الدماغية عند الاطفال في مستشفى حماية الاطفال/ بغداد.

Background: The annual incidence of stroke in children after the newborn period is approximately 2.3 per 100000. Half are ischemic, and half are non-traumaticintracerebral and subarchnoidal hemorrhages.Objectives: To study the etiologic factors, clinical presentation andoutcome of stroke among children admitted to children welfare teaching hospital/Baghdad.Patient and methods: A prospective study was carried out in Children Welfare Teaching Hospital;Children age ranged between 1 month -13 years and was admitted to pediatric neurology ward between 1st of November 2013 and 1st of November 2014. After carful clinical history, physical and neurological examinations, the diagnosis of brain stroke was confirmed in all patients by computerized tomography (CT) and/or magnetic resonance imaging (MRI). Patients included in this study were those diagnosed as having ischemic stroke, hemorrhagic stroke.Results: The total number of cases were 61, 36 were male (59%). The age at onset ranged from 1-156 months. Ischemic stroke constituted 39 patients (63.9%). The most common etiologic factors for the ischemic stroke were protein C deficiency (9, 23.1%). The most common etiologic factor for hemorrhage was bleeding disorders in about 50% of patients. The most common presenting features were hemiplegia, seizure, alteration of consciousness; Cranial nerves palsy is mostly present in the ischemic stroke (14,35.9%) and only in one patient (4.5%) of hemorrhagic stroke.Conclusions: Ischemic stroke is more common than hemorrhagic stroke in pediatric age group. The significant risk factors for ischemic stroke are protein C deficiency, Congenital heart disease(CHD) and positive family history, while vitamin K deficiency, prolong Partial thromboplastin time (PTT) and trauma are significant for hemorrhagic stroke. The most common clinical features of both types of stroke are hemiparesis, siezure and alteration of consciousness.

Ischemic Stroke in Children and Young Adults with Sickle Cell Disease (SCD) in the Post-STOP Era

Background: The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for children with abnormal TCD as standard of care. To identify children at high-risk of stroke, annual TCD screening is recommended from ages 2 to 16 years, with more frequent monitoring if the result is not normal. A reduction in stroke incidence in children with SCD has been reported in several clinical series and analyses utilizing large hospital databases when comparing rates before and after the publication of the STOP study in 1998. We sought to determine the rate of first ischemic stroke in a multicenter cohort of children who had previously participated in the STOP and/or STOP 2 trials and to determine whether these strokes were screening or treatment failures.Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3,835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 ranged from a single screening TCD to randomization. STOP 2 also had an observational arm for children on CRCT for abnormal TCD whose TCD had not reverted to normal. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both trials. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3,539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 (depending on site) including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two vascular neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results, reviewed source records to confirm all ischemic strokes, defined as a symptomatic cerebral infarction; discordant opinions were resolved through discussion. For the first Post-STOP ischemic stroke, prior TCD result and treatment history subsequently were analyzed.Results: Of the 3,539 subjects, follow-up data were available for 2,850 (81%). Twelve children who had a stroke during STOP or STOP2 were excluded from these analyses resulting in data on 2,838 subjects. The mean age at the start of Post-STOP was 10.5 y and mean duration of follow-up after exiting STOP/2 was 9.1 y. A total of 69 first ischemic strokes occurred in the Post-STOP observation period (incidence 0.27 per 100 pt years). The mean age at time of stroke was 14.4±6.2 (median 13.8, range 3.5-28.9) y. Twenty-five of the 69 patients (36%) had documented abnormal TCD (STOP/2 or Post-STOP) prior to the stroke; 15 (60%) were receiving CRCT and 9 (36%) were not (treatment data not available for 1 subject). Among the 44 subjects without documented abnormal TCD, 29 (66%) had not had TCD re-screen in the Post-STOP period prior to the event; 7 of these 29 (24%) were 16 y or older at the start of Post-STOP, which is beyond the recommended screening age. Four of the 44 (9%) patients had inadequate TCD in Post-STOP (1 to 10.7 y prior to event). Six (14%) had normal TCD more than a year before the event (1.2 - 4 y); all but one of these children were younger than 16 y at the time of that TCD. Only 5 (11%) had a documented normal TCD less than 1 year prior to the event.Conclusions: In the Post-STOP era, the rate of first ischemic stroke was substantially lower than that reported in the Cooperative Study of Sickle Cell Disease, prior to implementation of TCD screening. Many (39%) of the Post-STOP ischemic strokes were associated with a failure to re-screen according to current guidelines, while only 11% occurred in children who had had recent low-risk TCD. Among those known to be at high risk prior to stroke, treatment refusal or inadequate treatment may have contributed. While TCD screening and treatment are effective at reducing ischemic stroke in clinical practice, significant gaps in screening and treatment, even at sites experienced in the STOP protocol, remain to be addressed. Closing these gaps should provide yet further reduction of ischemic stroke in SCD. DisclosuresNo relevant conflicts of interest to declare.

Perinatal Stroke and Apparent Life-Threatening Event: A Case Report

To analyze how the multidisciplinary clinical, biohumoral, instrumental approach to ALTE (Apparent Life Threatening Event) episode may discover cardiovascular disease in the newborn. Introduction: In the first year of life ALTEs concern 0.8% of access to Pediatric Emergency Department. The cause of apparent life-threatening events (ALTEs) in infants reflects a differential diagnosis that includes an array of congenital or acquired disorders. Approximately 10% - 25% of ap-parent life-threatening events may remain unexplained following a thorough evaluation. Case re-port: B. E., a 2-month-old child, in wellbeing, shortly before meal, during sleep, was not responsive to repeated stimulations; he was hypotonic and unresponsive. About 15 minutes later, he pre-sented a normal tone and state of consciousness. Evaluating the referred symptoms, diagnostic protocol for ALTE was started; the Angio-MRI brain performed as second line analysis showed a focal gliotic lesion at left striatal area. The cardiological evaluation with echocardiography detected a pervium foramen ovale (PFO), with minimum shunt left-right direction. At least, biohumoral tests revealed protrombin gene heterozygosis mutation. Conclusion: Apparent Life-Threatening Events are first manifestation of stroke in infant. Discussion: This report discloses how the multidisciplinary clinical approach is essential in ALTE. The exact management of ALTE patients is very important in situations like this, when the concomitant disease is rare. In fact, arterial stroke incidence in children > 28 days of life is estimated between 1.2 and 7.9 cases/100,000 child-ren/year. However, in the last 20 years, we observed an increased incidence of stroke, probably related to two main causes: a greater attention for this disease and a major survival of children with pathology that arrange for stroke thanks to a better prevention. In conclusion, it’s a fundamental multidisciplinary approach even in following months after the events.

The Use Of Transcranial Doppler Ultrasonography In Adult Patients With Sickle Cell Disease: A Retrospective Analysis

Background Unlike in children, Transcranial Doppler Ultrasound (TCD) can not currently be used to predict stroke risk in adults with Sickle Cell Disease, and this is confounded by an age related decline in TCD and lack of an established normal TCD velocity range for adults. In addition abnormalities in the extracranial circulation have been associated with increased incidence of stroke in children with SCD, but this has not been shown in adults. Aims To retrospectively review TCD and carotid duplex ultrasound results from adults with SCD and to correlate with neurological outcome. Methods TCD and carotid duplex data were collected from 112 patients from January 2003 to December 2012 and analysed retrospectively. Imaging and non-imaging TCD and carotid duplex were performed as a routine out-patient investigation as part of an annual review in the comprehensive adult sickle cell clinic in our unit. STOP velocity criteria were used for stroke risk stratification. Carotid disease was defined as non-significant (&lt;50%), moderate stenosis (50-69%) and severe disease (≥70%). Results The mean age of patients was 35.4 (range 17-79) years; 65% were female and 78% had HbSS. There were 5 patient exclusions based on the TCD findings; two were non-diagnostic and three had abnormal scans as part of childhood screening. The remaining 107 patients were divided into two groups; Group I patients had a normal neurological examination (n = 95) and Group II had an abnormal neurological examination with a clinical diagnosis of stroke that preceded TCD/carotid duplex examination (n = 12). In Group I there were 4 abnormal TCD scans according to STOP criteria; two showed significant asymmetry (&gt;25%) and two showed abnormally low velocities (&lt;50cm/s), one of whom subsequently developed a silent stroke. Although the remaining 91 patients had normal TCD findings; a limited TCD examination was noted in 6 patients and asymmetrical velocities that fell below the 25% threshold were observed in 7 patients, one of whom subsequently developed a symptomatic lacunar infarct. A further eight patients showed extracranial (ICA) disease and one of these also had evidence of a silent stroke on MRI. In Group II, 5 patients showed abnormal TCD findings; four had low velocities (&lt;50cm/sec) and one had low velocities and significant asymmetry. Six patients had severe extracranial ICA stenosis or occlusion on carotid duplex. There was a significant increase in the incidence of abnormal TCD (C2=19.4, p&lt;0.001) and duplex findings (C2=16.2, p&lt;0.001) in patients in Group II compared to Group I. Conclusions Routine screening of adults with SCD using TCD did not show any asymptomatic patients with elevated TCD flow-velocities (&gt;170cm/s), confirming previous studies. However, other abnormal ultrasound findings were observed including; abnormally low or asymmetric TCD velocities and extracranial ICA disease. These abnormalities were associated with stroke in three cases; TCD asymmetry preceded a lacunar infarct by five years, abnormally low velocities preceded a silent infarct by two years and severe extracranial ICA stenosis was associated with a silent infarct. There was a significantly increased incidence of abnormal ultrasound findings in patients who had neurological symptoms (91.6% versus 12.6%). Further investigation of the incidence and implications of abnormal TCD and extracranial carotid duplex findings in adults with sickle cell disease is required. Longitudinal follow-up of patients with low or asymmetric velocities and ICA disease will clarify if these abnormalities are associated with increased neurological morbidity; if so, intervention may be justified. The traditional STOP criteria of raised TCD velocities are inadequate in the adult sickle population, new velocity criteria are required to stratify the risk of stroke in this population. Disclosures: Howard: Sangart: Membership on an entity’s Board of Directors or advisory committees.

Incremental Reduction in the Incidence of Stroke in Children Supported With the Berlin EXCOR Ventricular Assist Device

Cerebrovascular events (CVEs) are common among children supported with the Berlin EXCOR (Berlin Heart GmbH, Berlin, Germany) ventricular assist device (VAD). Given the high incidence of CVEs associated with this device, we sought to describe our institutional experience in incrementally reducing CVEs in children supported with the Berlin EXCOR VAD. We collected pertinent data on 39 consecutive patients who underwent Berlin EXCOR VAD implantation at a single center. Frequency of CVEs was described in risk per implantation, per day, and in reference to the time of therapeutic anticoagulation. Risk factors were analyzed for association with CVEs. Of the initial 39 Berlin EXCOR VAD implantations, 16 CVEs occurred in 12 patients. The incidence of CVEs decreased with institutional experience per patient (R(2) = 0.6909, p = 0.007) and per patient-day (R(2) = 0.8051, p = 0.002). CVEs occurred more frequently before therapeutic anticoagulation targets were achieved (4.1%/day) compared with after therapeutic anticoagulation targets were achieved (0.9%/day; p = 0.044). Incidence of CVEs decreased with institutional experience. The risk of CVE is highest in the immediate postoperative period before therapeutic anticoagulation is achieved. Further studies are warranted in pediatric patients supported with the Berlin EXCOR VAD to confirm our findings in a larger cohort.

Stroke in patients with sickle cell disease

Stroke is a significant cause of morbidity and mortality in children and adults with sickle cell disease. Great advances in the past couple of decades have enabled identification and treatment of children at risk of stroke, with a resultant dramatic reduction in stroke incidence in children. However, prevention and treatment of silent cerebral infarcts remain a challenge. This article reviews our current understanding of the epidemiology, risk factors and pathophysiology of small and large vessel disease with a focus on pediatric patients. The presentation and acute management of stroke in patients with sickle cell disease are discussed. Current recommendations for primary and secondary stroke prevention, as well as ongoing research studies and potential new therapies are reviewed.

Impact of Thrombophilia On Arterial Ischemic Stroke or Cerebral Venous Sinus Thromboses in Children: A Systematic Review & Meta-Analysis of Observational Studies.

Abstract 3993Poster Board III-929 BackgroundThe incidence of stroke in children is estimated at about 2.6 per 100,000 per year. Risk factors include congenital heart malformations, trauma, hemolytic anemias, collagen tissue diseases, inborn metabolic disorders, and infectious diseases. Apart from acquired thrombophilic risk factors, such as the presence of antiphospholipid antibodies, inherited thrombophilias (IT) have been found to be associated with stroke in infants and children. However, results of single studies on the risk of stroke onset associated with IT have been contradictory or inconclusive, mainly due to lack of statistical power. The aim of this study was to estimate the impact of thrombophilia (IT) on risk of childhood stroke via meta-analysis of published observational studies. Methods and ResultsA systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted using key words in combination both as MeSH terms and text words. Citations were independently screened by two authors and those meeting the a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, stroke type (arterial ischemic stroke [AIS]; cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed-effects and random-effects models. Twenty-one of 185 references found met inclusion criteria. 1698 patients (AIS: 1291; CSVT: 407) and 2913 controls aged neonate to 18 years were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with stroke onset was demonstrated for each IT trait evaluated, with no difference found between AIS (table) and CSVT. Summary ORs/CIs (random-effects model) for AIS & CSVT cohorts were as follows: Protein C-deficiency (8.76/4.53-16.96), FV G1691A (3.34/2.66-4.26), FII G20210A (2.50/1.67-3.74), MTHFR T677T (1.61/1.21-2.14), antiphospholipid antibodies (5.84/3.06-11.18), elevated lipoprotein (a) (6.24/4.51-8.64), and combined ITs (8.85/3.32-23.57). Carrier rates reported for antithrombin- or protein S deficiency among patients were 1.5% and 1.6% as compared with 0.06% (p<0.001) and 0.4% (p=0.003) in healthy controls. ConclusionsThe present meta-analysis indicates that IT serve as risk factors for incident stroke. However, the impact of IT upon outcome and recurrence risk needs to be further investigated.Table 1Summary odds ratios (ORs)/95%-confidence intervals (CIs: meta-analysis) including testing for heterogeneity (I2), non-combinability, and publication bias for thrombophilic risk factors associated with a first AIS onset in childrenIT [N of studies]patients / controls (N)OR/ CI; p-value: fixed modelOR/ CI; p-value: random modelI2 [%], p-valuebias indicator (Harbord):acquired risk factorsprotein C-def. [n=8]844/120711.0/5.13-23.599.74/4.61-20.570, p=0.96p=0.60APS/LA* [n=8]930/11946.95/3.67-13.145.84/3.05-11.170, p=0.82p=0.86genetic risk factorslipoprotein (a) [n=5]722/9096.27/4.52-8.696.24/4.51-8.640.0, p=0.91p=0.64FV G1691A [n=15]981/21903.70/2.82-4.853.75/2.85-4.920, p=0.67p=0.22FII G20210A [n=11]1000/18582.60/1.66-4.082.73/1.70-4.390, p=0.46p=0.78MTHFR TT** [n=10]718/12871.58/1.20-2.081.61/1.21-2.143.5, 0.40p=0.42> 2 genetic traits [n=9]701/126518.75/6.49-54.14;12.58/3.89-40.61;0, p=0.59p=0.61 Disclosures:Manco-Johnson:Baxter BioScience: Honoraria; Bayer HealthCare: Honoraria; CSL Behring: Honoraria; NovoNordisk: Honoraria; Octapharma: Honoraria. Off Label Use: Enoxaparin (LMWH) is used off-label in children to prevent symptomatic thromboembolism.

Caregivers' Perspectives on Barriers to Transcranial Doppler Screening in Children with Sickle Cell Disease.

Abstract 2473Poster Board II-450 Introduction:Children with HbSS or HbSβothalassemia have an 11% risk of stroke before the age of 20 without intervention. Transcranial Doppler ultrasonography (TCD) has been instrumental in detecting children with sickle cell disease (SCD) at high risk of stroke. Yearly TCD screenings are recommended for children with HbSS or HbSβothalassemia between the ages of 2 and 16 years. However, annual TCD compliance rates are very low. Our objective was to complete a qualitative, descriptive analysis of caregiver understanding, opinions, and barriers to their child's annual TCD screenings. Methods:The study consisted of interviewing 28 caregivers of children diagnosed with HbSS or HbSβothalassemia. The interviews were structured around a Health Belief Model (HBM) framework. The HBM describes the interaction of perceived susceptibility, perceived severity, perceived barriers, perceived benefits, cues to action, self-efficacy, demographic factors, and psychosocial factors which together produce the likelihood that an individual will take a recommended health action. The interviews consisted of both open response questions and Likert scale type questions where the caregiver agreed (“5”) or disagreed (“1”) with a statement. Topics covered during the interview included caregiver knowledge of TCD, adherence to screening guidelines, perceived susceptibility of their child to stroke, barriers that may prevent annual TCD screenings, perceived benefits to screening, and self-efficacy. The interviews were audio recorded and were later transcribed and coded. Common themes were extracted from the transcriptions. Results:61% of the interviewed caregivers reported that their child underwent a TCD in the past year. Many caregivers perceived their child as being at high risk for stroke, as over 60% thought that stroke occurred either “sometimes” or “frequently” in children with SCD. All of the interviewed caregivers saw benefits to TCD screening. We identified seven categories of barriers expressed by caregivers: lack of knowledge, lack of self-efficacy, fear, financial barriers, transportation barriers, missed appointments, and hours of radiology clinic. Three of the most frequently mentioned barriers included lack of knowledge, lack of self-efficacy, and fear of chronic transfusions. Lack of knowledge was reported to be a barrier by 32% of caregivers who reported having very limited knowledge about TCD testing or that they had forgotten the information previously provided to them. 46% of caregivers did not know that TCD screening was an annual test, and only one of the 28 caregivers knew that chronic transfusions would result if the TCD was consistently abnormal. Additionally, only one caregiver knew the age recommendations for screening. Caregivers also seemed to lack self-efficacy, as 18% of caregivers believed they had no role in stroke prevention and 50% did not realize that they could request that their doctor order an annual TCD test. Many caregivers (29%) believed that chronic transfusions could cause their child a lot of problems. Less frequently cited barriers included financial barriers, transportation barriers, missed appointments, and daytime/weekday hours of radiology clinic. Conclusions:The most commonly encountered barrier to TCD screening described by caregivers was the lack of knowledge of the purpose and recommendations for TCD screenings. We propose that health care providers provide ongoing education at each visit to caregivers regarding stroke risk, TCD screening, and the current recommendations for children with SCD. Some of the barriers identified in this study can easily be addressed to increase TCD compliance rates and decrease stroke incidence rates in children with SCD; for example, offering night and weekend radiology hours or identifying transportation issues prior to a TCD appointment and providing transportation when needed. Educating caregivers on the risks and benefits of chronic transfusions in stroke prevention could also prove beneficial in reducing caregiver fear of chronic transfusions. Strengthening the therapeutic alliance between the caregiver, child, and health care team is essential in order to increase caregiver compliance and self-efficacy with TCD screenings and decrease stroke incidence in children with SCD. Disclosures:No relevant conflicts of interest to declare.