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Infection, vaccination, and childhood arterial ischemic stroke: Results of the VIPS study
Abstract
Objectives:
Minor infection can trigger adult arterial ischemic stroke (AIS) and is common in childhood. We tested the hypotheses that infection transiently increases risk of AIS in children, regardless of stroke subtype, while vaccination against infection is protective.
Methods:
The Vascular Effects of Infection in Pediatric Stroke study is an international case-control study that prospectively enrolled 355 centrally confirmed cases of AIS (29 days-18 years old) and 354 stroke-free controls. To determine prior exposure to infections and vaccines, we conducted parental interviews and chart review.
Results:
Median (interquartile range) age was 7.6 years for cases and 9.3 for controls (p = 0.44). Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases, vs 3% of controls, conferring a 6.3-fold increased risk of AIS (p < 0.0001); upper respiratory infections were most common. Prevalence of preceding infection was similar across stroke subtypes: arteriopathic, cardioembolic, and idiopathic. Use of vasoactive cold medications was similarly low in both groups. Children with some/few/no routine vaccinations were at higher stroke risk than those receiving all or most (odds ratio [OR] 7.3, p = 0.0002). In an age-adjusted multivariate logistic regression model, independent risk factors for AIS included infection in the prior week (OR 6.3, p < 0.0001), undervaccination (OR 8.2, p = 0.0004), black race (compared to white; OR 1.9, p = 0.009), and rural residence (compared to urban; OR 3.0, p = 0.0003).
Conclusions:
Infection may act as a trigger for childhood AIS, while routine vaccinations appear protective. Hence, efforts to reduce the spread of common infections might help prevent stroke in children.
... Die Ursache für die unterschiedlichen Inzidenzen in den verschiedenen Altersstufen konnte bislang noch nicht eindeutig geklärt werden [23,43]. Im Kleinkindalter könnte das häufigere Auftreten von (banalen) Infektionen ein erhöhtes Risiko für einen AIS bedingen [17,60]. ...
... Infektionen scheinen ein wichtiger Risikofaktor für den kindlichen Schlaganfall zu sein [13,17,60]. Auch nach sog. ...
Zusammenfassung
Der arteriell ischämische Schlaganfall im Kindes- und Jugendalter gehört zu den zeitkritischsten Notfällen in der Pädiatrie. Dennoch wird er häufig mit einer oft prognostisch relevanten Zeitverzögerung diagnostiziert. Gründe dafür liegen neben der geringen Awareness auch in der zuweilen unspezifischen klinischen Präsentation mit einer herausfordernden Breite kritischer Differenzialdiagnosen sowie in der Fläche noch wenig verzahnter Akutversorgungsstrukturen. Gleichwohl zeigen grundsätzlich die beim Erwachsenen etablierten Revaskularisationsstrategien auch beim Kind ihre möglichen, zum Teil spektakulären Erfolge. Es gilt also, diese nach Möglichkeit auch den betroffenen Kindern zur Verfügung zu stellen, auch wenn hier derzeit ein nicht annähernd vergleichbarer Grad an Evidenz erreicht ist. Postakut ist die ätiologische Aufarbeitung durch die größere Bandbreite zu bedenkender Risikofaktoren besonders komplex, muss aber in der Lage sein, das individuelle Risikoprofil mit Sekundärprophylaxe, Rezidivrisiko und Outcome präzise zu identifizieren. Die Langzeitbetreuung im multiprofessionellen, interdisziplinären Team muss die biopsychosozialen Aspekte des Kindes in seiner jeweiligen Entwicklungsphase berücksichtigen und damit eine bestmögliche Integration des Kindes in sein soziales und schulisches, später berufliches Umfeld realisieren.
... 4 A comprehensive multicentre study (Vascular Effects of Infection in Pediatric Stroke [VIPS] study) with 355 children after stroke found that very low household income was associated with worse outcome using the Pediatric Stroke Outcome Measure, a standard neurological measure examining mental status; cranial nerves; motor, sensory, and cerebellar functions; and gait. 5 Maternal education level or type of residence (rural, urban) were not associated with neurological outcome in this study. ...
... Lastly, in previous studies, lower SES was not only associated with neurological outcome, but also with a higher incidence of childhood arterial ischemic stroke. 5 Could this association add to the worse cognitive outcome in children with low SES? Paediatric stroke is less influenced by typical adult risk factors including diabetes mellitus, arteriosclerosis, hypertension, or smoking. ...
Aim
To determine whether socioeconomic status (SES) is a stronger predictor for cognitive outcome after childhood arterial ischemic stroke compared to clinical factors.
Method
We investigated perceptual reasoning, executive functions, language, memory, and attention in 18 children and adolescents (12 males, six females, median age at testing 13y 4mo, range 7y–17y 5mo) after arterial ischemic stroke; collected sociodemographic information (education of parents, household income); and used clinical information (initial lesion volume, residual lesion volume, age at stroke, time since stroke). Linear regression models were used to investigate the potential influence of SES and clinical parameters on cognitive abilities.
Results
SES had a moderate effect on all cognitive outcome parameters except attention by explaining 41.9%, 37.9%, 38.0%, and 22.5% of variability in perceptual reasoning, executive functions, language, and memory respectively. Initial lesion volume was the only clinical parameter that showed moderate importance on cognitive outcome (33.1% and 25.6% of the variability in perceptual reasoning and memory respectively). Overall, SES was a stronger predictor of cognitive outcome than clinical factors.
Interpretation
Future paediatric studies aiming at clinical predictors of cognitive outcome should control their analyses for SES in their study participants. The findings of the present study further point to the need for more attention to the treatment of children with low SES.
... Carotid thrombi were not reported. In young adults or children, minor respiratory infections in the preceding week, have also been strongly associated with IS (OR 6.3 to 12.1) while vaccinations reduce the risk (19,20). However, these were case-control studies with no angiography data and mechanisms cannot be inferred. ...
... Moreover, the infection/IS association discussed above could arguably be mediated by cough-induced damage to the ICA in some of the cases, either similar to our patient or carotid artery dissections. This may explain why most infections reported in the context of IS are minor respiratory infections (20) and requires further study. ...
A healthy 19-year-old man with no risk factors presented with focal neurological symptoms (dysphasia and right hemiparesis) in the setting of an acute febrile illness and severe cough. Initial CTs showed pan-sinusitis and pulmonary infiltrates. The cerebrospinal fluid was normal. Human coronavirus OC43 was identified in nasal swabs. Repeat CTA/MRA revealed multiple infarcts in the territory of the left middle cerebral artery (MCA) and proximal intra-luminal left internal carotid artery filling defects due to thrombi were demonstrated. No thrombophilia was found and there are no reports of sinusitis-associated carotid thrombosis in the literature. Recent infection, in particular respiratory infection is a confirmed risk factor of ischemic stroke (IS) in adults and intriguingly, also in young patients. Myriad mechanisms have been demonstrated or postulated in the very young and our report suggests adding carotid thrombi. Previously described cough-induced carotid dissection could not be demonstrated, but similarly, cough-induced intimal injury of the carotid artery remains the most likely culprit, precipitating local thrombus formation and embolization.
... Carotid thrombi were not reported. In young adults or children, minor respiratory infections in the preceding week, have also been strongly associated with IS (OR 6.3 to 12.1) while vaccinations reduce the risk (19,20). However, these were case-control studies with no angiography data and mechanisms cannot be inferred. ...
... Moreover, the infection/IS association discussed above could arguably be mediated by cough-induced damage to the ICA in some of the cases, either similar to our patient or carotid artery dissections. This may explain why most infections reported in the context of IS are minor respiratory infections (20) and requires further study. ...
A healthy 19-year-old man with no risk factors presented with focal neurological symptoms (dysphasia and right hemiparesis) in the setting of an acute febrile illness and severe cough. Initial CTs showed pan-sinusitis and pulmonary infiltrates. The cerebrospinal fluid was normal. Human coronavirus OC43 was identified in nasal swabs. Repeat CTA/MRA revealed multiple infarcts in the territory of the left middle cerebral artery (MCA) and proximal intra-luminal left internal carotid artery filling defects due to thrombi were demonstrated. No thrombophilia was found and there are no reports of sinusitis-associated carotid thrombosis in the literature. Recent infection, in particular respiratory infection is a confirmed risk factor of ischemic stroke (IS) in adults and intriguingly, also in young patients. Myriad mechanisms have been demonstrated or postulated in the very young and our report suggests adding carotid thrombi. Previously described cough-induced carotid dissection could not be demonstrated, but similarly, cough-induced intimal injury of the carotid artery remains the most likely culprit, precipitating local thrombus formation and embolization.
... 12 Infection has been shown to play a major role in childhood AIS pathogeneses of all causes, including spontaneous cardioembolic stroke. 13 Both acute infection and prothrombotic conditions at the time of initial AIS presentation are predictive of AIS recurrence within a 10-year period in children with congenital heart disease. 14 At a 2014 symposium of Stroke in Children with Cardiac Disease, a collaborative group of pediatric cardiologists, hematologists, and neurologists prioritized further study of co-existing multiple risk factors as critical for the development of successful AIS prevention strategies. ...
... In the Vascular effects of Infection in Pediatric Stroke study, infection within the week before stroke increased the risk of AIS by 6.3fold, and was reported in 22% of the children with spontaneous cardioembolic AIS. 13 We cannot draw a causal relationship between acute systemic illness and AIS from our data, but further investigation into the role of acute systemic illness in AIS in children with cardiac disease is warranted. Elucidation of the mechanisms whereby infection might lead to AIS, including endocarditis or acquired prothrombotic states may improve early identification of cardiac patients who are at high risk for AIS. ...
Objective:
We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease.
Methods:
We identified children with cardiac causes of AIS enrolled in the International Pediatric Stroke Study registry from January 2003 to July 2014. Isolated patent foramen ovale was excluded. Peri-procedural AIS (those occurring during or within 72 hours of cardiac surgery, cardiac catheterization, or mechanical circulatory support) and spontaneous AIS that occurred outside of these time periods were compared.
Results:
We identified 672 patients with congenital or acquired cardiac disease as the primary risk factor for AIS. Among these, 177 patients (26%) had peri-procedural AIS and 495 patients (74%) had spontaneous AIS. Among non-neonates, spontaneous AIS occurred at older ages (median 4.2 years, interquartile range 0.97 to 12.4) compared with peri-procedural AIS (median 2.4 years, interquartile range 0.35 to 6.1, P < 0.001). About a third of patients in both groups had a systemic illness at the time of AIS. Patients who had spontaneous AIS were more likely to have a preceding thrombotic event (16 % versus 9 %, P = 0.02) and to have a moderate or severe neurological deficit at discharge (67% versus 33%, P = 0.01) compared to those with peri-procedural AIS.
Conclusions:
Children with cardiac disease are at risk for AIS at the time of cardiac procedures but also outside of the immediate 72 hours after procedures. Many have acute systemic illness or thrombotic event preceding AIS, suggesting that inflammatory or prothrombotic conditions could act as a stroke trigger in this susceptible population.
... These angiographic findings are more common in children with abnormal lipid profiles and familial cardiovascular disease [15]. The literature suggests associations between TCA and varicella infections [16], acute herpes virus infections [17] and other upper respiratory infections [18], though the impact of the inflammatory pathways in TCAs remains to be fully understood. There are other, rare causes of pediatric AIS that warrant discussion, including stroke secondary to genetic disorders such as pseudoxanthoma elasticum [19]. ...
Pediatric stroke is an important cause of mortality and morbidity in children. There is a paucity of clinical trials pertaining to pediatric stroke management, and solidified universal guidelines are not established for children the way they are for the adult population. Diagnosis of pediatric stroke can be challenging, and it is often delayed or mischaracterized, which can result in worse outcomes. Understanding risks and appropriate therapy is paramount to improving care.
... Viral infection has been described as a potential trigger of pediatric ischemic stroke. 18 Our study suggests that COVID-19 infection specifically could be a trigger, as rates of other pediatric viral infections were relatively low during our timeframe. 19 LVO strokes of the middle cerebral artery territories were the most common stroke type in both our pandemic and historical cohorts, which differs from other recent studies on pediatric stroke and COVID-19 infection, wherein focal cerebral arteriopathy was more implicated. ...
Background
There is an increased risk of stroke in adults with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection, but whether there is a similar association with stroke in children is unclear. Our objective was to determine whether there is a correlation between COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and pediatric ischemic stroke.
Methods
This was a retrospective, population-based cohort analysis between March 1, 2020, and June 30, 2021, conducted at a children's hospital. Pediatric patients with a diagnosis of ischemic stroke were identified using ICD-10 diagnoses of ischemic stroke, cerebrovascular accident, or cerebral infarction.
Results
We identified 16 patients, seven male and nine female, with ischemic stroke. Ages were 8 months to 17 years (median 11.5 years). More Asian (6%) and black (13%) patients had strokes compared with population prevalence (2% each, respectively). No patients had active COVID-19 infection. COVID-19 antibodies were identified in five of 11 patients tested (45%), of whom three were diagnosed with MIS-C. 82% of the strokes occurred between February and May 2021. The peak incidence was in February 2021, which was two months after peak incidence of pediatric cases of COVID-19 and one month after the peak of MIS-C cases.
Conclusions
Our study suggests that prior COVID-19 infection, but not acute infection, is correlated with a risk for stroke in the pediatric population. The risk for stroke appears to be distinct from the risk for MIS-C.
... Infektionen scheinen ein wichtiger Risikofaktor für den kindlichen Schlaganfall zu sein [24,33,34]. Auch nach "minor infections" wie z. ...
Childhood arterial ischemic stroke is one of the most time-critical pediatric emergencies but is often diagnosed with a prognostically relevant time delay. The reasons are low awareness, sometimes unspecific clinical presentation with a wide variety of critical differential diagnoses and less coordinated acute care structures. The revascularization strategies established for adults also show sometimes spectacular success in children. These should therefore also be made available for affected children if possible, although the evidence is nowhere near comparable. In the postacute phase the etiological work-up is complex due to the risk factors which need to be considered, but identification of the individual risk profile is essential as it defines secondary prevention, risk of recurrence and outcome. The long-term care in a multiprofessional, interdisciplinary team must take into account all bio-psycho-social aspects of the child in the current developmental phase.
... Many times, stroke is the result of cerebral ischemia and it is more common in the elderly. For children, arterial infection is the main cause of stroke (Fullerton et al., 2015(Fullerton et al., , 2017. Irreversible damage to brain tissue by stroke can lead to the death of a large number of brain cells within a few minutes, which is a great damage to neurological function, and leads to disability (Hornung and Sievert, 2021). ...
Choroid plexus epithelial cells can secrete cerebrospinal fluid into the ventricles, serving as the major structural basis of the selective barrier between the neurological system and blood in the brain. In fact, choroid plexus epithelial cells release the majority of cerebrospinal fluid, which is connected with particular ion channels in choroid plexus epithelial cells. Choroid plexus epithelial cells also produce and secrete a number of essential growth factors and peptides that help the injured cerebrovascular system heal. The pathophysiology of major neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, as well as minor brain damage diseases like hydrocephalus and stroke is still unknown. Few studies have previously connected choroid plexus epithelial cells to the etiology of these serious brain disorders. Therefore, in the hopes of discovering novel treatment options for linked conditions, this review extensively analyzes the association between choroid plexus epithelial cells and the etiology of neurological diseases such as Alzheimer's disease and hydrocephalus. Finally, we review CPE based immunotherapy, choroid plexus cauterization, choroid plexus transplantation, and gene therapy.
... 19 In the Vascular effects of infection in Pediatric Stroke (VIPS) study, upper respiratory tract infection developing the week prior to stroke is associated with 6.3-fold increased risk of AIS. 20 High prevalence of infection was noted in South America and Asia. 7 Infection was present in 40.5% of Bangladeshi children with stroke. ...
Global awareness of stroke as a significant cause of neurologic sequelae and death in children has increased over the years as more data in this field becomes available. However, most published literature on pediatric stroke have limited geographic representation. Data on childhood stroke from developing countries remains limited. Thus, this paper reviewed geographic/ethnic differences in pediatric stroke risk factors highlighting those reported in low- and middle-income countries, and proposes a childhood arterial ischemic stroke diagnostic algorithm for resource limited settings. Stroke risk factors include cardiac disorders, infectious diseases, cerebral arteriopathies, hematologic disorders, inflammatory diseases, thrombophilia and genetic conditions. Infection of the central nervous system particularly tuberculous meningitis, is a leading cause of pediatric arterial ischemic stroke in developing countries. Stroke should be considered in children with acute focal neurologic deficit especially in the presence of aforementioned risk factors. Cranial magnetic resonance imaging with angiography is the neuroimaging modality of choice but if unavailable, cranial computed tomography with angiography may be performed as an alternative. If both are not available, transcranial doppler together with neurologic exam may be used to screen children for arterial ischemic stroke. Etiological diagnosis follows with the aid of appropriate laboratory tests that are available in each level of care. International collaborative research on stroke risk factors that are prevalent in low and middle income countries will provide information for drafting of stroke care guidelines that are universal yet inclusive taking into consideration regional differences in available resources with the goal of reducing global stroke burden.
... Infektionen scheinen ein wichtiger Risikofaktor für den kindlichen Schlaganfall zu sein [24,33,34]. Auch nach "minor infections" wie z. ...
Childhood arterial ischemic stroke is one of the most time-critical pediatric emergencies but is often diagnosed with a prognostically relevant time delay. The reasons are low awareness, sometimes unspecific clinical presentation with a wide variety of critical differential diagnoses and less coordinated acute care structures. The revascularization strategies established for adults also show sometimes spectacular success in children. These should therefore also be made available for affected children if possible, although the evidence is nowhere near comparable. In the postacute phase the etiological work-up is complex due to the risk factors which need to be considered, but identification of the individual risk profile is essential as it defines secondary prevention, risk of recurrence and outcome. The long-term care in a multiprofessional, interdisciplinary team must take into account all bio-psycho-social aspects of the child in the current developmental phase.
... [4][5][6][7] Several causes of pediatric stroke like focal cerebral arteriopathy have inflammatory and/or infectious triggers. [8][9][10][11] Although it is plausible that SARS-CoV-2 could incite childhood strokes, to date, only 2 pediatric patients with the newly described multisystem inflammatory syndrome and 2 with arteriopathies in the setting of SARS-CoV-2 have been reported to have arterial ischemic stroke (AIS). 4,[12][13][14] With rising concern for SARS-CoV-2-related stroke among adults and inflammation among children, parent and caregiver anxieties are high. ...
OBJECTIVE: Severe complications of SARS-CoV-2 include arterial ischemic stroke (AIS) in adults and pediatric multisystem inflammatory syndrome. 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 pediatric strokes with SARS-CoV-2 in the first three 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) SARS-CoV-2 patients; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric stroke patients; and numbers of stroke cases positive for SARS-CoV-2 March 1-May 31, 2020. RESULTS: Of 42 centers with SAR-CoV-2 hospitalization numbers, 8/971 (0.82%) with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March-May 2020 were: 1/108 neonatal AIS (0.9%), 0/33 neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6/166 childhood AIS (3.6%), and 1/54 childhood CSVT (1.9%) cases. 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 eight 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 4.7% of pediatric ischemic stroke patients tested. However, <50% of strokes were tested. SARS-CoV-2 testing should be considered in pediatric stroke patients as the pandemic continues to determine SARS-CoV-2's role in pediatric stroke. This article is protected by copyright. All rights reserved.
... The term "non atherosclerotic arteriopathies" included a group of heterogeneous disorders resulting in lesions or structural abnormalities involving the cerebral blood vessels' wall as a consequence of infectious, parainfectious or inflammatory mechanisms but also genetic predisposition or vascular malformation (e.g., focal cerebral arteriopathy, PHACE, sickle cell disease, post-varicella arteriopathy, fibromuscular dysplasia) [17]. The VIPS (Vascular Effect of Infection In Pediatric Stroke Study) study identified viral infections in the prior week, recent vaccination, black ethnicity, and rural residence as risk factors for a higher occurrence of arterial ischemic stroke in children [18,19]. Serological evidence of recent, and mostly asymptomatic, herpesvirus infections were detected in 45% of the enrolled patients with a predominance of HSV1 and HSV2 over VZV (respectively 24.5% versus 11.3% of the cases) [20]. ...
This review provides an updated analysis of the main aspects involving the diagnosis and the management of children with acute ischemic stroke. Acute ischemic stroke is an emergency of rare occurrence in children (rate of incidence of 1/3500 live birth in newborns and 1–2/100,000 per year during childhood with peaks of incidence during the perinatal period, under the age of 5 and in adolescence). The management of ischemic stroke in the paediatric age is often challenging because of pleomorphic age-dependent risk factors and aetiologies, high frequency of subtle or atypical clinical presentation, and lacking evidence-based data about acute recanalization therapies. Each pediatric tertiary centre should activate adequate institutional protocols for the optimization of diagnostic work-up and treatments.
Conclusion : The implementation of institutional standard operating procedures, summarizing the steps for the selection of candidate for neuroimaging among the ones presenting with acute neurological symptoms, may contribute to shorten the times for thrombolysis and/or endovascular treatments and to improve the long-term outcome. What is Known: •Acute ischemic stroke has a higher incidence in newborns than in older children (1/3500 live birth versus 1–2/100,000 per year). •Randomized clinical trial assessing safety and efficacy of thrombolysis and/or endovascular treatment were never performed in children
What is New: •Recent studies evidenced a low risk (2.1% of the cases) of intracranial haemorrhages in children treated with thrombolysis. •A faster access to neuroimaging and hyper-acute therapies was associated with the implementation of institutional protocols for the emergency management of pediatric stroke.
... Some evidence suggests that minor evidence suggests that minor acute infection can act as a trigger for stroke of any type-arteriopathic, cardioembolic, or idiopathic. 42 These causes of paediatric stroke-distinct from those in adults and often multifactorial-present a major challenge for management, particularly when clinicians face decisions about whether to offer to a child a therapy or an intervention shown to benefit adults. ...
Paediatric arterial ischaemic stroke is an important cause of neurological morbidity in children, with consequences including motor disorders, intellectual impairment, and epilepsy. The causes of paediatric arterial ischaemic stroke are unique compared with those associated with stroke in adulthood. The past decade has seen substantial advances in paediatric stroke research and clinical care, but many unanswered questions and controversies remain. Shortage of prospective evidence for the use of recanalisation therapies in patients with paediatric stroke has resulted in little standardisation of disease management. Substantial time delays in diagnosis and treatment continue to challenge best possible care. In this Review, we highlight on some of the most pressing and productive aspects of research in the treatment of arterial ischaemic stroke in children, including epidemiology and cause, rehabilitation, secondary stroke prevention, and treatment updates focusing on advances in hyperacute therapies such as intravenous thrombolysis, mechanical thrombectomy, and critical care. Finally, we provide a future perspective for improving outcomes and quality of life for affected children and their families.
... На сегодняшний день существует достаточно большое количество исследований, подтверждающих влияние вируса ветряной оспы на последующие разви-тие острого нарушения мозгового кровообращения у детей [1][2][3][4][5][6][7]. Однако выявлено негативное влияние и других инфекционных заболеваний на развитие инсульта, таких, как острые респираторные вирусные инфекции [8], вирусы семейства Herpesviridae [9][10][11], энтеровирусные инфекции [12], бактериальные инфекции [13][14][15]. ...
Objective: Determine the role of infectious diseases in the development of strokes in children and to identify risk groups for its progression.
Materials and Methods : A retrospective analysis of 660 case histories of children aged 1 months to 1 8 years old, hospitalized in Morozov Children's City Clinical Hospital with stroke in the period from 201 6 to July 2020 was carried out.
Results. An infectious disease or fever 4 weeks before stroke is diagnosed in 78 (1 2%) cases. Infections more often act as a stroke trigger in children under 7 years old (28% in children under one year old). The incidence of strokes against a background of a bacterial infection is higher than against a background of a viral infection (47% versus 35%). Among bacterial infections, meningitis (35%), otitis media (24%), pneumonia (1 8%) prevailed. With a viral infection, viruses of Herpes are more common (44%), as well as respiratory viruses (37%). Two cases of cerebrovascular accident were revealed in children who have undergone a new coro-navirus infection SARS-CoV-2 (7%). Among the types of stroke, with bacterial infection, sinus thrombosis was more common (50%), among viral infection, the most common was ischemic stroke (60%). The presence of an additional risk factor was revealed in 72%, most often these were prothrombotic conditions (35%).
... In addition, vascular imaging was a requirement for inclusion in the VIPS study. 21 All images were centrally reviewed to confirm arterial ischemic stroke as part of the VIPS study. Ethical committee approvals were obtained at all participating centers. ...
BACKGROUND AND PURPOSE: To assess whether initial imaging characteristics independently predict 1-year neurological outcomes in childhood arterial ischemic stroke patients. METHODS: We used prospectively collected demographic and clinical data, imaging data, and 1-year outcomes from the VIPS study (Vascular Effects of Infection in Pediatric Stroke). In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging studies and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure. We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome. RESULTS: Univariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome. CONCLUSIONS: In the largest pediatric arterial ischemic stroke cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses but lost significance when adjusted for infarct volume. Our findings suggest that infarcts that disrupt critical networks have a disproportionate impact upon outcome after childhood arterial ischemic stroke.
... Although infection has been recognized as a risk factor for neonatal or childhood stroke [39], to the best of our knowledge, this is the first Table 4 Results of multivariable logistic regression analysis represented by adjusted odds ratios and 95% confidence intervals predicting the likelihood of overall adverse outcome and cerebral palsy/fine motor involvement in patients after excluding those with main branch MCA stroke. study that reports the presence of specific or non-specific inflammation as an independent predictor for adverse neurodevelopmental outcome, in particular CP, cognitive impairment and epilepsy in patients with NAIS. ...
Background
Neonatal arterial ischemic stroke (NAIS) carries the risk of significant long-term neurodevelopmental burden on survivors.
Aims
To assess the long-term neurodevelopmental outcome of term neonates diagnosed with NAIS and investigate the associations among brain territorial involvement on MRI, clinical risk factors and neurodevelopmental outcomes.
Study design
Population-based cohort study.
Subjects
Seventy-nine term neonates with NAIS confirmed by MRI born between 2007-2017.
Outcome measures
Long-term neurodevelopmental outcome assessed using the Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V.
Results
Follow-up was available in 70 (89%) of the subjects enrolled, at a median age of 60 months [IQR: 35-84]. Normal neurodevelopmental outcome was found in 43% of the patients. In a multivariable model, infants with main MCA stroke had an increased risk for overall adverse outcome (OR: 9.1, 95% CI: 1.7-48.0) and a particularly high risk for cerebral palsy (OR: 55.9, 95% CI: 7.8-399.2). The involvement of the corticospinal tract without extensive stroke also increased the risk for cerebral palsy/fine motor impairment (OR: 13.5, 95% CI: 2.4-76.3). Multiple strokes were associated with epilepsy (OR: 9.5, 95% CI: 1.0-88.9) and behavioral problems (OR: 4.4, 95% CI: 1.1-17.5) and inflammation/infection was associated with cerebral palsy (OR: 9.8, 95% CI: 1.4-66.9), cognitive impairment (OR: 9.2, 95% CI: 1.8-47.8) and epilepsy (OR: 10.3, 95% CI: 1.6-67.9).
Conclusions
Main MCA stroke, involvement of the corticospinal tract, multiple strokes and inflammation/infection were independent predictors of adverse outcome, suggesting that the interplay of stroke territorial involvement and clinical risk factors influence the outcome of NAIS.
... FCA is a pediatric entity frequently observed during or after viral infection, in which the infection is supposed to act as a trigger of a localized selflimited inflammatory course, usually without notable systemic inflammation. Therefore, one should not be surprised to observe FCA with SARS-CoV-2, as it is observed with varicella, herpesviruses, viral respiratory pathogens, etc. (25). Two children had stroke complicating pediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C), a pediatric condition related to uncontrolled inflammatory response and cytokine storm during or following infection with SARS-CoV-2 (8). ...
Neurologic manifestations associated with Covid-19 are increasingly reported, especially stroke and acute cerebrovascular events. Beyond cardiovascular risk factors associated with age, some young adults without medical or cardiovascular history had stroke as a presenting feature of Covid-19. Suggested stroke mechanisms in this setting are inflammatory storm, subsequent hypercoagulability, and vasculitis. To date, a handful of pediatric stroke cases associated with Covid-19 have been reported, either with a cardioembolic mechanism or a focal cerebral arteriopathy. We report the case of an adolescent who presented with febrile meningism and stupor. Clinical, biological, and radiological features favored the diagnosis of Lemierre syndrome (LS), with Fusobacterium necrophorum infection (sphenoid sinusitis and meningitis) and intracranial vasculitis. The patient had concurrent SARS-CoV-2 infection. Despite medical and surgical antimicrobial treatment, stroke prevention, and venous thrombosis prevention, he presented with severe cerebrovascular complications. Venous thrombosis and stroke were observed, with an extension of intracranial vasculitis, and lead to death. As both F. necrophorum and SARS-CoV-2 enhance inflammation, coagulation, and activate endothelial cells, we discuss how this coinfection may have potentiated and aggravated the usual course of LS. The potentiation by SARS-CoV-2 of vascular and thrombotic effects of a bacterial infection may represent an underreported cerebrovascular injury mechanism in Covid-19 patients. These findings emphasize the variety of mechanisms underlying stroke in this disease. Moreover, in the setting of SARS-CoV-2 pandemic, we discuss in what extent sanitary measures, namely, lockdown and fear to attend medical facilities, may have delayed diagnosis and influenced outcomes. This case also emphasizes the role of clinical assessment and the limits of telemedicine for acute neurological condition diagnosis.
... Infections are now recognized as a trigger for strokes in people of all ages (38,39), but this association may be even stronger among younger patients, including children (40,41) and young adults (42). This association has also been observed among pregnant and post-partum women. ...
Maternal mortality rates have been steadily increasing in the United States, and cardiovascular mortality is the leading cause of death among pregnant and postpartum women. Maternal stroke accounts for a significant burden of cardiovascular mortality. Data suggest that rates of maternal stroke have been increasing in recent years. Advancing maternal age at the time of birth and the increasing prevalence of traditional cardiovascular risk factors, and other risk factors, as well, such as hypertensive disorders of pregnancy, migraine, and infections, may contribute to increased rates of maternal stroke. In this article, we provide an overview of the epidemiology of maternal stroke, explore mechanisms that may explain increasing rates of stroke among pregnant women, and identify key knowledge gaps for future investigation in this area.
... [4][5][6][7] Several causes of pediatric stroke like focal cerebral arteriopathy have inflammatory and/or infectious triggers. [8][9][10][11] While plausible that SARS-CoV-2 could incite childhood strokes, to date only two pediatric patients with the newly described multisystem inflammatory syndrome and two with arteriopathies in the setting of SARS-CoV-2 have been reported to have arterial ischemic stroke (AIS). 4,[12][13][14] With rising concern for SARS-CoV-2-related stroke among adults and inflammation among children, parent and caregiver anxiety are high. ...
... [4][5][6][7] Several causes of pediatric stroke like focal cerebral arteriopathy have inflammatory and/or infectious triggers. [8][9][10][11] While plausible that SARS-CoV-2 could incite childhood strokes, to date only two pediatric patients with the newly described multisystem inflammatory syndrome and two with arteriopathies in the setting of SARS-CoV-2 have been reported to have arterial ischemic stroke (AIS). 4,[12][13][14] With rising concern for SARS-CoV-2-related stroke among adults and inflammation among children, parent and caregiver anxiety are high. ...
Objective
Severe complications of SARS‐CoV‐2 include arterial ischemic stroke (AIS) in adults and pediatric multisystem inflammatory syndrome. 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 pediatric strokes with SARS‐CoV‐2 in the first three 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) SARS‐CoV‐2 patients; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS‐CoV‐2 testing for pediatric stroke patients; and numbers of stroke cases positive for SARS‐CoV‐2 March 1–May 31, 2020.
Results
Of 42 centers with SAR‐CoV‐2 hospitalization numbers, 8/971 (0.82%) with SARS‐CoV‐2 had ischemic strokes. Proportions of stroke cases positive for SARS‐CoV‐2 from March–May 2020 were: 1/108 neonatal AIS (0.9%), 0/33 neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6/166 childhood AIS (3.6%), and 1/54 childhood CSVT (1.9%) cases. 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 eight 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 4.7% of pediatric ischemic stroke patients tested. However, <50% of strokes were tested. SARS‐CoV‐2 testing should be considered in pediatric stroke patients as the pandemic continues to determine SARS‐CoV‐2’s role in pediatric stroke.
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... In addition, vascular imaging was a requirement for inclusion in the VIPS study. 21 All images were centrally reviewed to confirm AIS as part of the VIPS study. Ethical committee approvals were obtained at all participating centers. ...
Background and Purpose
To assess whether initial imaging characteristics independently predict 1-year neurological outcomes in childhood arterial ischemic stroke patients.
Methods
We used prospectively collected demographic and clinical data, imaging data, and 1-year outcomes from the VIPS study (Vascular Effects of Infection in Pediatric Stroke). In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging studies and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure. We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome.
Results
Univariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome.
Conclusions
In the largest pediatric arterial ischemic stroke cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses but lost significance when adjusted for infarct volume. Our findings suggest that infarcts that disrupt critical networks have a disproportionate impact upon outcome after childhood arterial ischemic stroke.
... The limitations include the difference between vessel size in children and adults that make some clot retrieval devices out of use. Besides, stroke mechanisms differ in children from adults, mostly focal cerebral arteriopathy, sickle cell arteriopathy, and moyamoya, which are not amenable to thrombectomy (21,28,29). ...
Context: Based on current literature, there is no consensus regarding the proper management of pediatric acute ischemic stroke (P-AIS); and there are lots of considerable controversies in this regard. Therefore, the current review was conducted to provide a more comprehensive discussion in this topic.
Evidence acquisition: The search was conducted using terms “pediatrics”, “stroke” and “recombinant tissue plasminogen activator” in PubMed database. English language papers on management of P-AIS published after 2000 were selected. A critical appraisal was performed in an expert panel to summarize the findings and make them applicable. Finally, the extracted data were categorized in subheadings and the manuscript was prepared.
Results: There are limited evidence on the topic; all extracted findings are categorized as follows: Etiology and the underlying diseases, clinical presentations, diagnosis, management (thrombolytic therapy and thrombectomy) and outcome.
Conclusion: It seems that although thrombolytic therapy is recommended in P-AIS, but since most of the cases are diagnosed outside the therapeutic window, this treatment is practically impossible, so they are candidate for mechanical interventions. On the other hand, proper device may not be available to fit the size of younger child's vasculature.
... Stroke is very rare in children, but an international case-control study found a 6-fold increased risk of ischemic stroke in children suffering from an infection, mainly respiratory, in the week prior to the stroke. The stroke risk was higher in unvaccinated or partly vaccinated children compared to those receiving all or most routine vaccinations [27]. ...
Influenza affects millions of patients every year. The manifestations vary from mild respiratory symptoms to severe pulmonary and extra-pulmonary complications and even death. Recent scientific evidence has been accumulating that influenza infection can trigger acute myocar-dial infarction and stroke. Both diseases are the leading causes of death worldwide, and the recognition of the risk factors is crucial for adequate prevention. This article reviews the pathogenetic links between influenza and the development of myocardial infarction and stroke. It presents the incidence, timing and outcome of these acute cardiovascular events after influenza infection and the role of vaccination for their prevention. The aim of the review is to focus the attention of medical practitioners on the association between influenza and cardiovascular events in order to improve the prevention and management of high-risk patients.
... These results support the hypothesis that VZV may be a causative organism in the pathogenesis of giant cell arteritis, 34 although further confirmation is needed. VZV has also been associated with focal cerebral arteriopathy and stroke in children, 35 and zoster has been associated with an acute increase in risk of stroke in adults; vaccination against varicella was protective against stroke in retrospective analyses in children, 36 although whether zoster vaccine prevents stroke in adults is less certain. 37 HIV may also cause cerebral vasculopathy, although patients with HIV may have strokes for many other reasons, including other opportunistic infections, comorbid vascular risk factors, and side effects, such as dyslipidemia, of antiretroviral therapy. ...
Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.
... Akhir akhir ini, infeksi saluran pernafasan akut bagian atas juga ditemukan sebagai faktor risiko. 4,[9][10][11][12] Infeksi HIV dapat menyebabkan stroke secara sekunder akibat vaskulitis dan vaskulopati dengan aneurisma atau perdarahan akibat trombositopenia. Mikroorganisme yang dihubungkan dengan stroke pada anak adalah mycoplasma, chlamydia, enterovirus, parvovirus 19, influenza A, coxsackie, dll. ...
Stroke adalah kerusakan neuronal akibat oklusi atau pecahnya pembuluh darah serebral. Stroke dapat iskemik, hemoragik atau kombinasi keduanya. Stroke iskemik lebih sering disebabkan oleh oklusi arteri, tetapi dapat juga disebabkan oleh oklusi vena vena cerebral atau sinus. Stroke hemoragik dapat terjadi akibat perdarahan dari arteri cerebri yang pecah atau perdarahan di tempat stroke iskemik akut (AIS). Sekitar 10-25% anak akan meninggal akibat komplikasi stroke, lebih dari 25% stroke pada anak akan berulang dan lebih dari 66% akan menimbulkan kejang atau defisit neurologik yang menetap dan masalah tumbuh kembang anak. Stroke pada anak seringkali kurang dikenali, walaupun telah dilakukan
berbagai usaha untuk meningkatkan kewaspadaan. Stroke pada anak sering tidak terdiagnosis atau salah diagnosis. Hal ini terjadi karena berbagai faktor yang menyebabkan keterlambatan dalam diagnosis. Dilaporkan 19 dari 45 anak dengan stroke tidak terdiagnosis dengan benar 15 jam sampai 3 bulan setelah timbul gejala awal. Pengenalan lebih dini stroke pada anak akan mempercepat konsultasi ke neurologi anak, lebih cepat dilakukan pemeriksaan pencitraan (imaging) dan tentu saja akan mempercepat tatalaksana dan selanjutnya meningkatkan luaran.
... Even "minor infections" like upper respiratory tract infections or otitis media have been shown to increase the risk for ischaemic stroke up to sixfold. [37][38][39] Ischaemic stroke is also a known complication in bacterial or tuberculous meningitis. In general, a broad list of infectious pathogens can trigger the above-described transient focal arteriopathy leading to a stroke. ...
Childhood arterial ischaemic stroke (AIS) is a rare, but potentially life-threatening event which requires early diagnosis and adequate treatment. The reported significant time delay to childhood AIS diagnosis may be associated with low awareness, the more nonspecific clinical presentation as well as difficult clinical differentiation to more common "stroke mimics" and a less established "acute care structure" with delayed access to proper neuroimaging. Compared with adult stroke care, experiences with acute reperfusion therapies like thrombolysis and mechanical thrombectomy are promising but limited and not based on clinical trials. The etiological work-up is absolutely essential, as the child's individual risk profile determines acute management, secondary prevention, risk of recurrence and outcome. Follow-up care should be organized in a multidisciplinary setting covering all bio-psycho-social aspects to achieve the best integration of the child into its educational, later professional and social environments.
Georg Thieme Verlag KG Stuttgart · New York.
... This was an international case-control study that prospectively enrolled 355 centrally confirmed cases of AIS (29 days to 18 years of age) and 354 stroke-free controls. Infection in the week prior to stroke was reported in 18% of cases versus 3% of controls, conferring a 6.3-fold increase risk of AIS (p< 0.0001), with upper respiratory infections being the most common, followed by gastroenteritis, followed by otitis media (Fullerton et al., 2015). Of note, children with some/few/no routine vaccinations were at higher stroke risk than those receiving all or most, suggesting that routine vaccinations appeared to be protective. ...
We stand on the shoulders of giants on the threshold of many new exciting developments in the field of child neurology due to innovations in clinical approach, diagnostic technologies and treatment strategies. There are many exciting new technologies, but we must never forget the power of clinical medicine which allows us to interpret and use these tools with precision and with clinical wisdom. Strong collaborations continue to be needed: between clinicians for the meticulous clinical phenotyping, expansion of the range of phenotypic expression, and the entry of patients into international RCTs (randomised controlled trials); between the biochemists for the biochemical phenotyping and understanding of the basic pathophysiology of the underlying dysregulations and disease mechanisms arising from the protein dysfunctions and the development of robust biomarkers, to evaluate disease severity and response to therapies; and between the geneticists for the understanding of the impact of the exonic or intronic mutations, roles of other regulatory genes on the affected pathway, and epigenetic factors. These collaborations in the aggregate will lead the field forward in terms of increased insight into disease pathophysiology for the development of targeted precision medicine treatment strategies and effective preventative measures. This review is meant to highlight certain selected areas of future development and is not meant to be a comprehensive survey beyond the scope of this review. The subspecialty areas which will be highlighted will include intellectual disability, epilepsy, neuroprotection, neonatal and fetal neurology, CNS infections, headache, autoimmune/inflammatory disorders, demyelinating disorders, stroke, movement disorders, neurotransmitter defects, neuromuscular diseases, neurometabolic disorders, neurogenetic diseases, neuropsychiatry/autism, and neurooncology. In each subspecialty area, I will endeavor to identify emerging diseases, new specific diagnostic technologies and novel therapeutic approaches, but will need to be selective. This review is the culmination of a literature survey for current developments, discussions with leaders in each of the subspecialty fields, who I will acknowledge at the end, and certain personal projections.
... Our data show incidence of AIS peaks in infants, very young children and adolescence without significant differences in risk factor categories. Our results could not support the hypothesis that infants and toddlers are at a higher risk of infectious diseases and therefor at higher risk for para-infectious vasculopathies leading to an ischemic stroke [47][48][49]. Indeed, our case report form may have missed some mild upper respiratory tract infections up to one week before the stroke event, but considering the results of other studies, pediatricians were expected to report a higher proportion of vasculopathies in stroke patients in the younger age group. ...
Objective
Childhood arterial ischaemic stroke (AIS) is rare, but causes significant morbidity and mortality. We aimed to investigate incidence, age-dependent clinical presentation, and risk factors and to discuss the medical care situation in Germany.
Methods
This prospective epidemiological study was conducted via ESPED (Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland), a hospital-based German nation-wide surveillance unit for rare pediatric diseases. Children aged 28 days–18 years with first AIS between January 2015 and December 2017 were included.
Results
In the 3-year period, 164 children were reported. Incidence showed peaks in infants, children < 2 years of age, and adolescents (12–18 years), with a significant male predominance observed in adolescents only. Independent of age, most children (91%) presented with focal symptoms, particularly with acute hemiparesis. The occurrence of seizures in infants (57%) and more nonspecific symptoms in school-children and adolescents (54%) is considered noteworthy. Prothrombotic states (34%), cardiac disorders (29%), and arteriopathies (19%) were the most frequently identified risk factors. The majority of children (72/131, thus 55%) were discharged home after acute care phase. At time of discharge, most common neurological symptoms were hemiparesis (42%), facial palsy (15%), and speech disturbance (12%).
Conclusion
This study provides population-based data of childhood AIS which may be useful for further research. The improvement of acute stroke management is needed for children, but also the standardization of post-stroke care in the outpatient setting has to be structured. Considering the higher stroke incidence in (male) adolescents, it is advisable to combine research activities in adolescents and young adults.
... 27 Interestingly, respiratory infections, which have been associated with IS in other studies, were uncommon in our cohort. 20,28,29 However, it is notable that the influenza subgroup was the only infection subgroup to show a statistically significant difference between the stroke and nonstroke groups. This finding is consistent with prior studies in other populations that have shown that influenza is associated with particular risk for IS, and raises the possibility that improving influenza vaccination rates among pregnant women might reduce the risk of postpartum stroke. ...
Background and Purpose—
Most cases of pregnancy-related ischemic stroke (IS) and hemorrhagic stroke (HS) occur postpartum. Infections have been identified as a trigger for strokes in young people and have been associated with strokes during delivery hospitalizations, but a temporal relationship has been difficult to establish. We hypothesized that infections diagnosed during a delivery admission would be associated with an increased risk of readmission for postpartum stroke.
Methods—
We conducted a retrospective cohort study using the Healthcare Cost and Utilization Project’s National Readmissions Database from 2010 to 2014. Using weighted survey design Poisson regression analysis, we calculated adjusted risk ratios (aRR) and 95% CI for the association between infection during delivery admission and 30-day postpartum readmission for IS or HS.
Results—
Out of 17.2 million delivery admissions during the study period, 2128 were readmitted within 30 days for a stroke of any type. There were 1189 HS (intracerebral hemorrhage or subarachnoid hemorrhage) and 720 IS, and the remainder unspecified pregnancy-related stroke. Adjusting for age and comorbidities, women with delivery infections were at higher risk of readmission for postpartum stroke of any type (aRR, 1.19; 95% CI, 1.01–1.41). Women with infections had higher risk of readmission for postpartum IS (aRR, 1.75; 95% CI, 1.37–2.22), but not for postpartum HS (aRR, 0.96; 95% CI, 0.75–1.23). The effect of infection on 30-day IS readmission was larger in women without hypertensive disorders of pregnancy (aRR, 2.0; 95% CI, 1.55–2.69 in women without hypertensive disorders of pregnancy versus aRR, 1.47; 95% CI, 0.9–2.38 in women with hypertensive disorders of pregnancy, P value for interaction=0.09).
Conclusions—
Infection during delivery hospitalization was associated with increased risk of readmission for IS, but not HS, within 30 days postpartum, particularly in women without hypertensive disorders of pregnancy. Infection may play a role in triggering postpartum IS even in the absence of other risk factors.
... Poor oral intake and dehydration may have been contributing complicating factors, although the patient's blood urea nitrogen/creatinine ratio was normal on initial laboratory assessments. Fullerton et al. also found that infection transiently increased the risk of childhood AIS, with as many as 39% of patients with AIS reporting infection in the preceding 4 weeks and 18% in the preceding 1 week (adjusted odds ratio 6.5 [95% confidence interval 3.3-13] for infection in the previous week) (8). ...
Background:
Acute ischemic stroke (AIS) in pediatric populations accounts for more than half of pediatric strokes and is associated with significant morbidity and mortality. Pediatric AIS can present with nonspecific symptoms or symptoms that mimic alternate pathology.
Case report:
A 4-month-old female presented to the emergency department for fever, decreased oral intake, and "limp" appearance after antibiotic administration. She was febrile, tachypneic, and hypoxic. Her skin was mottled with 3-s capillary refill, her anterior fontanelle was tense, and she had mute Babinski reflex bilaterally but was moving all extremities. The patient was hyponatremic, thrombocytopenic, and tested positive for influenza A. A computed tomography scan of the brain revealed an acute infarction involving the right frontal, parietal, temporal, and occipital lobes in addition to hyperdensities concerning for thrombosed cortical veins. The patient was transferred for specialty evaluation and was discharged 2 weeks later on levetiracetam. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pediatric AIS can present with nonspecific symptoms that mimic alternate pathology. A high level of suspicion is needed so as not to miss the diagnosis of pediatric AIS in the emergency department. A thorough neurologic assessment is warranted, and subtle abnormalities should be investigated further.
... [6][7][8] Childhood infections, including Varicella Zoster virus, have been shown to be associated with an increased risk of AIS, with routine vaccinations being protective against AIS. 9,10 In addition, the presence of prothrombotic risk factors has been found in small case series and case control studies to be associated with ischaemic stroke in children, with this association confirmed by meta-analysis. 11 This is in contrast to perinatal stroke, in which recent studies have not shown an association with thrombophilia 12 and recurrence is relatively rare. ...
Purpose of review:
The purpose of this review is to review recent findings regarding stroke epidemiology, etiologies, and treatment in children and young adults.
Recent findings:
Incidence in young adults is increasing, and incidence, recurrence, and survival is worse in patients with cryptogenic stroke and in developing countries. Careful consideration of patent foramen ovale closure is now recommended in young adults with cryptogenic stroke. Thrombectomy has recently been extended to carefully selected children with acute ischemic stroke, and two recent publications strongly suggest that it can be beneficial for children. Sickle cell is also an important global contributor to stroke burden, but hydroxyurea can be a cost effective medication for stroke prevention in children. Recent advances in genetic testing and treatments may improve outcomes for patients with monogenic causes of stroke, such as deficiency of adenosine deaminase 2, hemophilia, and Fabry's disease.
Summary:
Stroke in children and young adults is a morbid disease responsible for enormous indirect societal costs and a high burden of years with disability per affected patient. Recent advances have improved access to care for children with large vessel occlusion and adults with rare causes of stroke. Future research may bring effective treatments for other monogenic causes of stroke as well as increasing access to hyperacute therapies for young stroke patients.
Over the past few decades, robust clinical and research collaborations among pediatric stroke researchers have informed and improved the care of children with stroke. Risk factors and presentation of childhood stroke have been described, and the acute and chronic burden of childhood stroke has been better delineated. Nevertheless, high-quality data for treatment of children with stroke is dwarfed by that available for adult stroke, and it is therefore tempting to extend research questions and treatment trials from adults to children. A trial designed to answer a question about stroke in adults may yield useful information about stroke in childhood, but a trial that incorporates the unique neurodevelopmental and etiological aspects of childhood stroke is more likely to truly advance care. Research questions and study design in childhood stroke must capture the complexity of stroke mechanisms and medical comorbidities in children who suffer stroke, the impact on the developing nervous system, as well as the role of normal and aberrant neurodevelopment on recovery.
Up to more than half of previously healthy children presenting with their first arterial ischemic stroke have a cerebral arteriopathy. Cerebral arteriopathies during childhood can be congenital, reflecting abnormal vessel development, or acquired when caused by disruption of vascular homeostasis. Distinguishing different types of cerebral arteriopathies in children can be challenging but of great clinical value as they may dictate different disease and treatment courses, and clinical and radiologic outcomes. Furthermore, children with stroke due to a specific arteriopathy exhibit distinctive features when compared to those with stroke due to other causes or a different type of arteriopathy. These features become crucial in the management of pediatric stroke by choosing appropriate diagnostic and treatment strategies. The objective of this article is to provide the reader with a comprehensive up-to-date review of the classification, symptoms, diagnosis, treatment, and outcome of cerebral arteriopathies in children.
Childhood stroke is not as common as adult stroke, but it is underrecognised the world over. Diagnosis is often delayed due to lack of awareness not only by the lay public but also by emergency and front-line health care workers. Despite the relative rarity of childhood stroke, the impact on morbidity, mortality and the economic burden for families and society is high, especially in poorly resourced settings. The risk factors for stroke in children differ from the adult population where lifestyle factors play a more important role. The developmental aspects of the paediatric cerebral vasculature and haematological maturational biology affects the clinical presentation, investigation, management and outcomes of childhood stroke in a different way compared to adults. The management of childhood stroke is currently based on expert guidelines and evidence extrapolated from adult studies. Hyperacute therapies that have revolutionised the treatment of stroke in adults cannot be easily applied to children at this stage due to the diagnostic delays, diverse risk factors and developmental considerations mentioned above. Much has been achieved in the understanding of genetic, acquired, preventable and recurrent stroke risk factors in the past decade through international collaborative efforts like the International Paediatric Stroke Study (IPSS). Evidence for the prevention and treatment of childhood stroke remains elusive. Even more elusive are relevant and achievable management guidelines for paediatric stroke in resource-limited settings. This narrative review focusses on the current management practices globally, emphasizing the challenges, and gaps in knowledge of paediatric stroke in low- and middle-income countries (LMICs) and other areas with limited resources. Priorities and some potential solutions at national and local level are suggested for these settings.
Infections play an important role in the pathogenesis of acute ischemic stroke (AIS) in neonates and children. In neonates, chorioamnionitis or intrauterine inflammation has been implicated as a common risk factor for AIS. In infants and children, recent investigations demonstrated that even minor childhood infections are associated with subsequent increased risk for AIS. Post-infectious inflammatory mechanisms following infections with herpesviruses may lead to focal cerebral arteriopathy (FCA), one of the most common causes of AIS in a previously healthy child. Other agents such as parvovirus B19, dengue virus, and SARS-CoV-2 have recently been implicated as other potential triggers.
Infections are compelling treatable stroke risk factors, with available therapies for both pathogens and downstream inflammatory effects. However, infections are common in childhood, while stroke is uncommon. The ongoing VIPS II (Vascular effects of Infection in Pediatric Stroke) study aims to identify the array of pathogens that may lead to childhood AIS and whether either unusual strains or unusual combinations of pathogens explain this paradox. Immune modulation with corticosteroids for FCA is another active area of research, with European and U.S. trials launching soon. The results of these new pediatric stroke studies combined with findings emerging from the larger field of immune-mediated post-infectious diseases will likely lead to new approaches for the prevention and treatment of pediatric stroke.
This review highlights recent developments from both clinical and animal model research enhancing our understanding of this relationship between infection, inflammation, and stroke in neonates and children.
Since the onset of the coronavirus disease 2019 pandemic, a variety of neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in patients, of which one of the most concerning is stroke. This review aims to summarize the current literature and evolving understanding of pediatric cerebrovascular complications in the setting of SARS-CoV-2.
Stroke is an important cause of neurological morbidity in children; most survivors have permanent neurological deficits that affect the remainder of their life. Stroke in childhood, the focus of this Primer, is distinguished from perinatal stroke, defined as stroke before 29 days of age, because of its unique pathogenesis reflecting the maternal–fetal unit. Although approximately 15% of strokes in adults are haemorrhagic, half of incident strokes in children are haemorrhagic and half are ischaemic. The causes of childhood stroke are distinct from those in adults. Urgent brain imaging is essential to confirm the stroke diagnosis and guide decisions about hyperacute therapies. Secondary stroke prevention strongly depends on the underlying aetiology. While the past decade has seen substantial advances in paediatric stroke research, the quality of evidence for interventions, such as the rapid reperfusion therapies that have revolutionized arterial ischaemic stroke care in adults, remains low. Substantial time delays in diagnosis and treatment continue to challenge best possible care. Effective primary stroke prevention strategies in children with sickle cell disease represent a major success, yet barriers to implementation persist. The multidisciplinary members of the International Pediatric Stroke Organization are coordinating global efforts to tackle these challenges and improve the outcomes in children with cerebrovascular disease. This Primer summarizes the mechanisms, epidemiology, diagnosis and treatment of stroke in children (that is, stroke occurring in those aged between 29 days and 18 years).
Objectives:
To define the incidence and characteristics of influenza-associated neurologic complications in a cohort of children hospitalized at a tertiary care pediatric hospital with laboratory-confirmed influenza, and to identify associated clinical, epidemiologic, and virologic factors.
Study design:
Historical cohort study of children 0.5-18.0 years-old hospitalized between 2010-2017 with laboratory-confirmed influenza. Children with immune compromise or a positive test due to recent receipt of live virus vaccine or recently resolved illness were excluded. Influenza-associated neurologic complications were defined as new-onset neurologic signs/symptoms during acute influenza illness without another clear etiology.
Results:
At least one influenza-associated neurologic complication was identified in 10.8% (95% CI 9.1-12.6%, n=131 of 1,217) of hospitalizations with laboratory-confirmed influenza. Seizures (n=97) and encephalopathy (n=44) were the most commonly identified influenza-associated neurologic complication, although an additional 20 hospitalizations had other influenza-associated neurologic complications. Hospitalizations with influenza-associated neurologic complications were similar in age and influenza type (A/B) to those without. Children with a pre-existing neurologic diagnosis (n=326) had a higher proportion of influenza-associated neurologic complications compared with those without (22.7% vs 6.4%, p<0.001). Presence of a pre-existing neurologic diagnosis (aOR 4.6, P < .001), lack of seasonal influenza vaccination (aOR 1.6, p=0.020), and age ≤5 years (aOR 1.6, p=0.017) were independently associated with influenza-associated neurologic complications.
Conclusions:
Influenza-associated neurologic complications are common in children hospitalized with influenza, particularly those with pre-existing neurologic diagnoses. A better understanding of the epidemiology and factors associated with influenza-associated neurologic complications will direct future investigation into potential neuropathologic mechanisms and mitigating strategies. Vaccination is recommended and may help prevent influenza-associated neurologic complications in children.
The cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.
Background and Purpose
Focal cerebral arteriopathy (FCA) of childhood with unilateral stenosis of the anterior circulation is reported to account for up to one-quarter of childhood arterial ischemic stroke, with stroke recurrence in 25% of cases. Limited knowledge regarding pathophysiology and outcome results in inconsistent treatment of FCA.
Methods
Children with arterial ischemic stroke due to FCA between January 1, 2009, and January 1, 2019, were retrospectively identified at our institution which serves the US Pacific Northwest region. Electronic health record data, including neuroimaging studies, were reviewed, and the Pediatric Stroke Outcome Measure at 1 year was determined as the primary clinical end point.
Results
Fifteen children were diagnosed with FCA, accounting for 19% of children with cerebral arteriopathies (n=77). Among children with FCA, the median age at the time of stroke was 6.8 years (Q1–Q3, 1.9–14.0 years). Four (20%) patients had worsening stroke, 3 of whom had concurrent infection. Three (20%) FCA cases were treated with steroids, one of whom had worsening stroke. Median Pediatric Stroke Outcome Measure at 1 year was 1.0 (Q1–Q3, 0.6–2.0). Variability in arteriopathy severity was observed within many patients. Patients with more severe arteriopathy using the Focal Cerebral Arteriopathy Severity Score had larger strokes and were more likely to have worsening stroke. The most common long-term neurological deficit was hemiparesis, which was present in 11 (73%) patients and associated with middle cerebral artery arteriopathy and infarcts.
Conclusions
FCA may be less common than previously reported. Neuroimaging in FCA can help identify patients at greater risk for worsening stroke.
Childhood arterial ischemic stroke differs in essential aspects from adult stroke. It is rare, often relatively unknown among laypersons and physicians and the wide variety of age-specific differential diagnoses (stroke mimics) as well as less established care structures often lead to a considerable delay in the diagnosis of stroke. The possible treatment options in childhood are mostly off-label. Experiences in well-established acute treatment modalities in adult stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in children and only based on case reports and case series. The etiological clarification is time-consuming due to the multitude of risk factors which must be considered. Identifying each child’s individual risk profile is mandatory for acute treatment and secondary prevention strategies and has an influence on the individual outcome. In addition to the clinical neurological outcome the residual neurological effects of stroke on cognition and behavior are decisive for the integration of the child into its educational, later professional and social environment.
Introduction:
Acute infections are known triggers of cardiovascular disease (CVD) but how this association varies across infection types is unknown. We hypothesized while acute infections increase CVD risk, the strength of this association varies across infection types.
Method:
Acute coronary heart disease (CHD) and ischemic stroke cases were identified in the Atherosclerosis Risk in Communities Study (ARIC). ICD-9 codes from Medicare claims were used to identify cellulitis, pneumonia, urinary tract infections (UTI), and bloodstream infections. A case-crossover design and conditional logistic regression were used to compare infection types among acute CHD and stroke cases 14, 30, 42, and 90 days before the event with two corresponding control periods (1 and 2 years prior).
Results:
Of the 1312 acute CHD cases, 116 had a UTI, 102 had pneumonia, 43 had cellulitis, and 28 had a bloodstream infection 90 days before the CHD event. Pneumonia (OR = 25.53 (9.21,70.78)), UTI (OR = 3.32 (1.93, 5.71)), bloodstream infections (OR = 5.93 (2.07, 17.00)), and cellulitis (OR = 2.58 (1.09, 6.13)) were associated with higher acute CHD risk within 14 days of infection. Of the 727 ischemic stroke cases, 12 had cellulitis, 27 had pneumonia, 56 had a UTI, and 5 had a bloodstream infection within 90 days of the stroke. Pneumonia (OR = 5.59 (1.77, 17.67)) and UTI (OR = 3.16 (1.68, 5.94)) were associated with higher stroke risk within 14 days of infection.
Conclusions:
Patients with pneumonia, UTI, or bloodstream infection appear to be at a 2.5 to 25.5 fold elevated CVD risk following infection. Preventive therapies during this high-risk period should be considered.
Several populations of patients deserve further attention related to unique risk factors and treatment paradigms. Stroke used to be a disease of the elderly. It is now seen increasingly in younger patients, as well as other subpopulations such as pregnant women and cancer patients. These patients provide their own challenges in terms of workup and management. Many treatment options for acute stroke are cautiously adopted from adult studies, simply because it has been understudied in these populations. This chapter will outline key points in stroke management for these patients.
Purpose of review:
Focal cerebral arteriopathy (FCA) is one of the most common causes of arterial ischaemic stroke in a previously healthy child. Distinguishing between different subtypes of arteriopathy is challenging and has significant management implications.
Recent findings:
Recent studies have helped to define the subtypes of focal cerebral arteriopathies and improved understanding of their clinical and radiological features. In addition, they have reported new evidence for the association between viral infection and inflammation in the pathogenesis of FCA and proposed new radiological, serum and cerebrospinal fluid biomarkers to guide diagnosis and management. There is limited evidence to guide treatment of FCA but a role for steroids and antiviral therapies have been reported.
Summary:
Despite the recent advances there is a limited knowledge of the pathophysiology and outcomes following FCA. Research priorities include the identification of biomarkers to improve accuracy of initial diagnosis and predict progression, and interventional trials to determine best treatments to reduce stroke recurrence risk.
Background
In recent years, there has been increasing research interest in improving diagnostic and management protocols in childhood arterial ischaemic stroke (AIS). However, childhood stroke comprises, in approximately equal parts, both arterial ischaemic and haemorrhagic stroke (HS).
Objective
The aim of this study was to focus on the aetiology, clinical presentation, treatment and short-term outcome of children with spontaneous intracranial bleeding in a university hospital and elucidate differences to childhood AIS.
Design
We performed a retrospective analysis of electronic medical records of children (28 days–18 years) diagnosed with HS between 2010 and 2016.
Results
We included 25 children (male child, n=11) with a median age of 8 years 1 month. The most common clinical presentations were vomiting (48%), headache (40%) and altered level of consciousness (32%). In more than half of the patients, HS was caused by vascular malformations. Other risk factors were brain tumour, coagulopathy and miscellaneous severe underlying diseases. Aetiology remained unclear in one child. Therapy was neurosurgical in most children (68%). Two patients died, 5 patients needed further (rehabilitation) treatment and 18 children could be discharged home.
Conclusions
HS differs from AIS in aetiology (vascular malformations as number one risk factor), number of risk factors (‘mono-risk’ disease), clinical presentation (vomiting, headache and altered level of consciousness) and (emergency) therapy.
Background and purpose:
Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.
Methods:
Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.
Results:
Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78).
Conclusions:
Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.
Understanding the vascular injury pathway is crucial to developing rational strategies for secondary stroke prevention in children. The multicenter Vascular Effects of Infection in Pediatric Stroke (VIPS) cohort study will test the hypotheses that (1) infection can lead to childhood arterial ischemic stroke by causing vascular injury and (2) resultant arteriopathy and inflammatory markers predict recurrent stroke. The authors are prospectively enrolling 480 children (aged 1 month through 18 years) with arterial ischemic stroke and collecting extensive infectious histories, blood and serum samples (and cerebrospinal fluid, when clinically obtained), and standardized brain and cerebrovascular imaging studies. Laboratory assays include serologies (acute and convalescent) and molecular assays for herpesviruses and levels of inflammatory markers. Participants are followed prospectively for recurrent ischemic events (minimum of 1 year). The analyses will measure association between markers of infection and cerebral arteriopathy and will assess whether cerebral arteriopathy and inflammatory markers predict recurrent stroke.
To determine the association between a composite measure of serological test results for common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2) and stroke risk in a prospective cohort study.
Prospective cohort followed up longitudinally for median 8 years.
Northern Manhattan Study. Patients Randomly selected stroke-free participants from a multiethnic urban community. Main Outcome Measure Incident stroke and other vascular events.
All 5 infectious serological results were available from baseline samples in 1625 participants (mean [SD] age, 68.4 [10.1] years; 64.9% women). Cox proportional hazards models were used to estimate associations of each positive serological test result with stroke. Individual parameter estimates were then combined into a weighted index of infectious burden and used to calculate hazard ratios and confidence intervals for association with risk of stroke and other outcomes, adjusted for risk factors. Each individual infection was positively, though not significantly, associated with stroke risk after adjusting for other risk factors. The infectious burden index was associated with an increased risk of all strokes (adjusted hazard ratio per standard deviation, 1.39; 95% confidence interval, 1.02-1.90) after adjusting for demographics and risk factors. Results were similar after excluding those with coronary disease (adjusted hazard ratio, 1.50; 95% confidence interval, 1.05-2.13) and adjusting for inflammatory biomarkers.
A quantitative weighted index of infectious burden was associated with risk of first stroke in this cohort. Future studies are needed to confirm these findings and to further define optimal measures of infectious burden as a stroke risk factor.
We performed a case-control study to investigate the role of recent infection as stroke risk factor and to identify pathogenetic pathways linking infection and stroke. We examined 166 consecutive patients with acute cerebrovascular ischemia and 166 patients hospitalized for nonvascular and noninflammatory neurologic diseases. Control subjects were individually matched to patients for sex, age, and season of admission. We assessed special biochemical parameters in subgroups of stroke patients with and without recent infection (n = 21) who were similar with respect to demographic and clinical parameters. Infection within the preceding week was a risk factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1; 95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of recent infection and age were inversely related. Both bacterial and viral infection contributed to increased risk. Infection elevated the risk for cardioembolism and tended to increase the risk for arterioarterial embolism. Stroke patients with and without preceding infection were not different with respect to factor VII and factor VIII activity, fibrin monomer, fibrin D-dimer, von Willebrand factor, C4b-binding protein, protein S, anticardiolipin antibodies, interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor, interleukin-6, interleukin-8, and neopterin. In conclusion, recent infection is an independent risk factor for acute cerebrovascular ischemia. Its role appears to be more important in younger age groups. The pathogenetic linkage between infection and stroke is still insufficiently understood.
OBJECTIVE:
To describe presumptive risk factors (RFs) for childhood arterial ischemic stroke (AIS) and explore their relationship with presentation, age, geography, and infarct characteristics.
METHODS:
Children (29 days-18 years) were prospectively enrolled in the International Pediatric Stroke Study. Risk factors, defined conditions thought to be associated with childhood AIS, were divided into 10 categories. Chi-square tests were used to compare RFs prevalence across regions and age; logistic regression was used to determine whether RFs were associated with particular features at presentation or infarct characteristics.
RESULTS:
A total of 676 children were included. No identifiable RFs was present in 54 (9%). RFs in others included arteriopathies (53%), cardiac disorders (CDs) (31%), infection (24%), acute head and neck disorders (AHNDs) (23%), acute systemic conditions (ASCs) (22%), chronic systemic conditions (CSCs) (19%), prothrombotic states (PTSs) (13%), chronic head and neck disorders (CHNDs) (10%), atherosclerosis-related RFs (2%), and other (22%). Fifty-two percent had multiple RFs. There was lower prevalence of arteriopathy in Asia, lower prevalence of CSCs in Europe and Australia, higher prevalence of PTSs in Europe, and higher prevalence of ASCs in Asia and South America. Prevalence of CDs and ASCs was highest in preschoolers, arteriopathies in children 5 to 9 years old, and CHNDs were highest in children aged 10 to 14 years. Arteriopathies were associated with focal signs and ASCs, CHNDs, and AHNDs with diffuse signs. Arteriopathies, CSCs, and ASCs were associated with multiple infarcts and CDs with hemorrhagic conversion.
INTERPRETATION:
RFs, especially arteriopathy, are common in childhood AIS. Variations in RFs by age or geography may inform prioritization of investigations and targeted preventative strategies.
We present data on the known risk factors encountered in children presenting with a first arterial ischemic stroke to a single tertiary center over 22 years. Two hundred twelve patients (54% male; median age, 5 years) were identified. One hundred fifteen (54%) were previously healthy. Cerebral arterial imaging was undertaken in 185 patients (87%) and was abnormal in 79%. Of 104 previously healthy patients investigated with echocardiography, only 8 had abnormal studies. Genetic or acquired conditions causing thrombophilia were rare. Forty percent of patients were anemic, and 21% either had elevated total plasma homocysteine or were homozygous for the t-MTHFR mutation. Trauma and previous varicella zoster infection were significantly more common in the previously healthy group. There was a significant association between cerebral arterial abnormalities and systolic blood pressure greater than 90th percentile and a trend for an association with varicella within the previous year. Clinical history and examination usually identify underlying risk factors and precipitating triggers for arterial ischemic stroke in childhood. Cerebral arterial imaging is usually abnormal, but echocardiography and prothrombotic screening are commonly negative
Objective:
In a population-based case-control study, we examined whether the timing and number of minor infections increased risk of childhood arterial ischemic stroke (AIS).
Methods:
Among 102 children with AIS and 306 age-matched controls identified from a cohort of 2.5 million children in a large integrated health care plan (1993-2007), we abstracted data on all medical visits for minor infection within the 2 years prior to AIS or index date for pairwise age-matched controls. We excluded cases of AIS with severe infection (e.g., sepsis, meningitis). Using conditional logistic regression, we examined the effect of timing and total number of minor infections on stroke risk.
Results:
After adjusting for known pediatric stroke risk factors, the strongest association between infection and AIS was observed for infectious visits ≤3 days prior to stroke (odds ratio [OR] 12.1, 95% confidence interval [CI] 2.5, 57, p = 0.002). Respiratory infections represented 80% of case infections in that time period. Cases had more infectious visits, but not significantly so, for all time periods ≥4 days prior to the stroke. A greater cumulative number of infectious visits over 2 years did not increase risk of AIS.
Conclusions:
Minor infections appear to have a strong but short-lived effect on pediatric stroke risk, while cumulative burden of infection had no effect. Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury. The transient effect of infection in children may suggest a greater role for a prothrombotic mechanism.
Background
Cerebrovascular benefits using the 23-valent pneumococcal polysaccharide vaccine (PPV23) are controversial. This study assessed clinical effectiveness of PPV23 in preventing ischemic stroke in people older than 60 years.
Methods
We conducted a population-based cohort study involving 27,204 individuals of 60 years or older in Tarragona, Spain, who were prospectively followed from December 01, 2008, until November 30, 2011. Outcomes were neuroimaging-confirmed ischemic stroke, 30-day mortality from stroke, and all-cause death. Pneumococcal vaccination effectiveness was evaluated by Cox regression analyses, estimating hazard ratios (HRs) adjusted for age, sex, comorbidities, and influenza vaccine status.
Results
Cohort members were followed for a total of 76,033 person-years, of which 29,065 were for vaccinated subjects. Overall, 343 cases of stroke, 45 deaths from stroke, and 2465 all-cause deaths were observed. Pneumococcal vaccination did not alter the risk of stroke (multivariable HR: 1.04; 95% confidence interval [CI]: .83-1.30; P = .752), death from stroke (HR: 1.14; 95% CI: .61-2.13; P = .686), and all-cause death (HR: .97; 95% CI: .89-1.05; P = .448). In analyses focused on people with and without a history of cerebrovascular disease, the PPV23 did not emerge effective in preventing any analyzed event, but influenza vaccine emerged independently associated with a reduced risk of death from stroke (HR: .51; 95% CI: .28-.93; P = .029) and all-cause death (HR: .73; 95% CI: .67-.81; P < .001).
Conclusions
Our data support that the PPV23 does not provide benefit against ischemic stroke, but it also supports a beneficial effect of influenza vaccine in reducing specific- and all-cause mortality risk in the general population older than 60 years.
Trauma and acute infection have been associated with stroke in adults, and are prevalent exposures in children. We hypothesized that these environmental factors are independently associated with childhood arterial ischemic stroke (AIS).
In a case-control study nested within a cohort of 2.5 million children (≤19 years old) enrolled in an integrated health care plan (1993-2007), childhood AIS cases (n = 126) were identified from electronic records and confirmed through chart review. Age- and facility-matched controls (n = 378) were randomly selected from the cohort. Exposures were determined from review of medical records prior to the stroke diagnosis, or the same date for the paired controls; time windows were defined a priori.
A medical encounter for head or neck trauma within the prior 12 weeks was an independent risk factor for childhood AIS (odds ratio [OR], 7.5; 95% confidence interval [CI], 2.9-19.3), present in 12% of cases (1.6% of controls). Median time from trauma to stroke was 0.5 days (interquartile range, 0-2 days); post hoc redefinition of trauma exposure (prior 1 week) was more strongly associated with AIS: OR, 39; 95% CI, 5.1-298. A medical encounter for a minor acute infection (prior 4 weeks) was also an independent risk factor (OR, 4.6; 95% CI, 2.6-8.2), present in 33% of cases (13% of controls). No single infection type predominated. Only 2 cases had exposure to trauma and infection.
Trauma and acute infection are common independent risk factors for childhood AIS, and may be targets for stroke prevention strategies. ANN NEUROL 2012;72:850-858.
Background:
Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities.
Methods:
We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both.
Results:
Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis.
Conclusions:
Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers.
Previous studies have demonstrated that infections might precipitate ischemic strokes (IS). We sought to describe, in a large prospective series, the frequency of previous infection (PI) in IS and intracerebral hemorrhage (ICH), and to assess whether any relationship with stroke subtype or outcome could be identified.
Between January 2005 and December 2010, we studied 1,981 patients with acute stroke. The presence of PI within the month before the stroke was prospectively assessed. PI was correlated with demographic data, vascular risk factors, stroke subtype, and 3-month outcome.
A total of 193 (9.7%) patients had suffered a PI, the most common being respiratory tract infections (36.8%), flu or flu-like illness (30.1%), and gastrointestinal infections (12.4%). PI was more frequent in IS cases (10.2%) than in ICH (6.8%) (p = 0.081). Among IS cases, no differences were seen between PI and TOAST subtypes (p = 0.644). For IS, patients with PI were older (p = 0.025), had worse previous functional status (p = 0.002), suffered a more severe stroke (p = 0.002), achieved poor outcome (p = 0.001), and had higher 3-month mortality (p = 0.019). Multivariate analysis showed that IS patients with PI had previous poor functional status (OR = 1.58; p = 0.026) and suffered more severe strokes (OR = 1.02, p = 0.048). After adjustment for confounders, PI has no independent influence on 3-month outcome (OR = 1.15; p = 0.564).
PI are observed in 9.7% of stroke cases without differences according to the TOAST subtype. PI are associated with previous poor functional status and with stroke severity, but have no independent influence on the 3-month outcome.
Little is known about the acute precipitants of ischemic stroke, although evidence suggests infections contribute to risk. We hypothesized that acute hospitalization for infection is associated with the short-term risk of stroke.
The case-crossover design was used to compare hospitalization for infection during case periods (90, 30, or 14 days before an incident ischemic stroke) and control periods (equivalent time periods exactly 1 or 2 years before stroke) in the Cardiovascular Health Study, a population-based cohort of 5888 elderly participants from 4 US sites. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by conditional logistic regression. Confirmatory analyses assessed hazard ratios of stroke from Cox regression models, with hospitalization for infection as a time-varying exposure.
During a median follow-up of 12.2 years, 669 incident ischemic strokes were observed in participants without a baseline history of stroke. Hospitalization for infection was more likely during case than control time periods; for 90 days before stroke, OR=3.4 (95% CI, 1.8 to 6.5). The point estimates of risks were higher when we examined shorter intervals: for 30 days, OR=7.3 (95% CI, 1.9 to 40.9), and for 14 days, OR=8.0 (95% CI, 1.7 to 77.3). In survival analyses, risk of stroke was associated with hospitalization for infection in the preceding 90 days, adjusted hazard ratio=2.4 (95% CI, 1.6 to 3.4).
Hospitalization for infection is associated with a short-term increased risk of stroke, with higher risks observed for shorter intervals preceding stroke.
The occurrence of stroke in populations is incompletely explained by traditional vascular risk factors. Data from several case-control studies and one large study using case series methodology indicate that recent infection is a temporarily acting, independent trigger factor for ischemic stroke. Both bacterial and viral infections, particularly respiratory tract infections, contribute to this association. A causal role for infection in stroke is supported by a graded temporal relationship between these conditions, and by multiple pathophysiological pathways linking infection and inflammation, thrombosis, and stroke. Furthermore, observational studies suggest that influenza vaccination confers a preventive effect against stroke. Case-control and prospective studies indicate that chronic infections, such as periodontitis, chronic bronchitis and infection with Helicobacter pylori, Chlamydia pneumoniae or Cytomegalovirus, might increase stroke risk, although considerable variation exists in the results of these studies, and methodological issues regarding serological results remain unresolved. Increasing evidence indicates that the aggregate burden of chronic and/or past infections rather than any one single infectious disease is associated with the risk of stroke. Furthermore, genetic predispositions relating to infection susceptibility and the strength of the inflammatory response seem to co-determine this risk. Here, we summarize and analyze the evidence for common acute and chronic infectious diseases as stroke risk factors.
Prior annualized estimates of pediatric ischemic stroke incidence have ranged from 0.54 to 1.2 per 100,000 US children but relied purely on diagnostic code searches to identify cases. We sought to obtain a new estimate using both diagnostic code searches and searches of radiology reports and to assess the relative value of these 2 strategies.
Using the population of 2.3 million children (<20 years old) enrolled in a Northern Californian managed care plan (1993 to 2003), we performed electronic searches of (1) inpatient and outpatient diagnoses for International Classification of Diseases, 9th Revision codes suggestive of stroke and cerebral palsy; and (2) radiology reports for key words suggestive of infarction. Cases were confirmed through chart review. We calculated sensitivities and positive predictive values for the 2 search strategies.
We identified 1307 potential cases from the International Classification of Diseases, 9th Revision code search and 510 from the radiology search. A total of 205 ischemic stroke cases were confirmed, yielding an ischemic stroke incidence of 2.4 per 100,000 person-years. The radiology search had a higher sensitivity (83%) than the International Classification of Diseases, 9th Revision code search (39%), although both had low positive predictive values. For perinatal stroke, the sensitivity of the stroke International Classification of Diseases, 9th Revision codes alone was 12% versus 57% for stroke and cerebral palsy codes combined; the radiology search was again the most sensitive (87%).
Our incidence estimate doubles that of prior US reports, a difference at least partially explained by our use of radiology searches for case identification. Studies relying purely on International Classification of Diseases, 9th Revision code searches may underestimate childhood ischemic stroke rates, particularly for neonates.
Ischemic stroke is a known complication of varicella disease. Although there have been case reports of ischemic stroke after varicella vaccination, the existence and magnitude of any vaccine-associated risk has not been determined. OBJECTIVE. The purpose of this work was to determine whether varicella vaccination is associated with an increased risk of ischemic stroke and encephalitis in children within 12 months after vaccination.
We conducted a retrospective cohort study based on computerized data from children 11 months through 17 years old enrolled for > or =12 months in the Vaccine Safety DataLink from 1991 through 2004. International Classification of Disease codes identified cases of ischemic stroke (433-436, 437.1, 437.4, 437.6, 437.8-437.9) and encephalitis (052.0, 323.5, 323.8-9). Cox regression was used to model the risk in the 12 months after vaccination relative to all other person-time. Covariates included calendar time, gender, and stroke risk factors (eg, sickle cell disease).
Varicella vaccine was administered to 35.3% of the 3.2 million children in the cohort. There were 203 new inpatient ischemic stroke diagnoses, including 8 that occurred within 12 months after vaccination; there was no temporal clustering. The adjusted stroke hazard ratio was not elevated during any of the time periods in the 12 months after vaccination. Stroke was strongly associated with known risk factors such as sickle cell disease and cardiac disease. None of the 243 encephalitis cases occurred during the first 30 days after vaccination, and there was no association between encephalitis and varicella vaccination at any time in the 12 months after vaccination.
Our retrospective cohort study of >3 million children found no association between varicella vaccine and ischemic stroke.
Acute and chronic infections may play a role in promoting complications of atherosclerotic disease. We evaluated the importance of acute infections and chronic bronchitis (CB; as a chronic inflammatory state) in several subtypes of ischemic stroke, and we investigated whether the influenza vaccination was independently associated with a reduced likelihood of stroke.
A case-control study was performed on 393 consecutive ischemic stroke patients and 393 control subjects matched for age, sex and time of year. Data were collected by a structured interview that assessed risk factors, acute infections within the preceding 2 months, CB and whether they had received the influenza vaccination.
Infections within the 2 months before stroke onset and CB were more common among patients than control subjects [23.3 vs. 16.3% (p = 0.014) and 17.2 vs. 8.5% (p = 0.001), respectively]. After adjustment for traditional risk factors, the risk of stroke was increased in the subjects with CB (OR = 1.83, 95% CI = 1.35-2.48, p = 0.016), but not with acute infection (OR = 1.32, 95% CI = 0.98-1.78, p = 0.16). Acute infections and CB increased the risk of ischemic events in all age groups; this reached significance for patients older than 60 years. The profile of vascular risk factors was similar in patients with and without previous infections. The influenza vaccination did not prevent ischemic stroke, and it did not reduce the rate of acute previous infections in stroke patients.
CB and infections over the previous 2 months predicted the risk of ischemic stroke. The influenza vaccination was not associated with a reduction in the incidence of stroke in our group of patients.
The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample was analysed for standard biochemical variables and serum cholesterol, high density lipoprotein cholesterol, triglyceride, and fasting blood glucose concentrations determined. Titres of antimicrobial antibodies against various bacteria, including Staphylococcus, Streptococcus, Yersinia, and Salmonella and several viruses were determined. Febrile infection was found in patients during the month before the brain infarction significantly more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9.0 (95% confidence interval 2.2 to 80.0)). The most common preceding febrile infection was respiratory infection (80%). Infections preceding brain infarction were mostly of bacterial origin based on cultural, serological, and clinical data. In conditional logistic regression analysis for matched pairs the effect of preceding febrile infection remained significant (estimated relative risk 14.5 (95% confidence interval 1.9 to 112.3)) when tested with triglyceride concentration, hypertension, smoking, and preceding intoxication with alcohol. Although causality cannot be inferred from these data and plausible underlying mechanisms remain undetermined, preceding febrile infection may play an important part in the development of brain infarction in young and middle aged patients.
Previous infection is discussed as a risk factor for ischemic stroke in children and younger adults. We tested the hypothesis that the role of recent infection in cerebrovascular ischemia is not restricted to younger patients and investigated which infections are mainly relevant in this respect.
We performed a case-control study with 197 patients aged 18 to 80 years with acute cerebrovascular ischemia and 197 randomly selected control subjects matched for sex, age, and area of residence.
Infection within 1 week before ictus or examination was significantly more common among patients (38 of 197) than control subjects (10 of 197; odds ratio [OR], 4.5; 95% confidence interval [CI], 2.1 to 9.7). Patients more often had febrile and subfebrile infections (> or = 37.5 degrees C) than control subjects (29 of 197 versus 5 of 197; OR, 7.0; 95% CI, 2.5 to 20). Respiratory tract infections were most common in both groups. Bacterial infections dominated among patients but not among control subjects. Infection increased the risk for cerebrovascular ischemia in all age groups; this reached significance for patients aged 51 to 60 and 61 to 70 years. The profile of vascular risk factors was similar in patients with and patients without previous infection. Infection remained a significant risk factor when previous stroke, hypertension, diabetes mellitus, coronary heart disease, and current smoking were included as covariates in a logistic model (OR, 4.6; 95% CI, 1.9 to 11.3).
Recent infection, primarily of bacterial origin, may be a risk factor for cerebrovascular ischemia in older as well as younger patients.
Cerebrovascular ischemia can be caused by infectious diseases which involve cerebral arteries or the heart, including infectious endocarditis, bacterial and fungal meningitis, neurosyphilis, neuroborreliosis, herpes zoster, the acquired immunodeficiency syndrome, cat scratch disease and other rare infectious diseases. Presently, there is increasing evidence that infection in general and mainly respiratory infection is a risk factor for ischemic stroke. Case reports and smaller case series reported an association of cerebrovascular ischemia and recent infection in children and younger adults. Two case control studies from Helsinki (54 patients under the age of 50) and from Heidelberg (197 patients aged 80 or less) identified recent infection as an important risk factor for ischemic stroke. Febrile, bacterial and respiratory infections were most important in this respect. In the study from Heidelberg, the neurological deficit was more severe and cardioembolism was more frequent in infection-associated stroke than in stroke without preceding infection. This review summarizes the association of infectious diseases and cerebrovascular ischemia and discusses potential pathogenetic mechanisms linking both diseases.
Antecedent febrile infection and psychological stress are described as predisposing risk factors for brain infarction. We examined the temporal relationship between preceding infection/inflammation and stroke onset as well as the role of recent psychological stress as a potential precipitant for brain infarction.
In this case-control study, a standardized evaluation including a signs/symptoms-based questionnaire was used to characterize the prevalence and timing of recent prior (< 1 month) infectious and inflammatory syndromes in 37 adults with acute brain infarction, 47 community control subjects, and 34 hospitalized nonstroke neurological patient controls. Recent psychological stress was measured with scales of stressful life events and negative affect.
The prevalence of infection/inflammation was significantly higher in the stroke group only within the preceding 1 week compared with either community control subjects (13/37 versus 6/47, P < .02) or hospitalized neurological patient controls (3/34, P < .02). Upper respiratory tract infections constituted the most common type of infection. A substantial proportion of stroke patients with preceding (< 1 week) infection/inflammation (5/13) had no accompanying fever or chills. There were no significant differences between the stroke and control groups in the levels of stressful life events within the prior 1 month or in negative-affect scale scores within the prior 1 week.
Our data suggest that both febrile and nonfebrile infectious/inflammatory syndromes may be a common predisposing risk factor for brain infarction and that the period of increased risk is confined within a brief temporal window of less than 1 week. Results of this study argue against a role for recent psychological stress as a precipitant for cerebral infarction.
Prior studies have demonstrated that infections might precipitate ischemic strokes (IS), but the role of infection as a risk factor remains unclear. We conducted a case-control study to investigate this issue.
Consecutive patients (n = 182) with acute IS were examined within 48 hours after admission to our center. A history of acute infections within 2 months before the IS was assessed by means of a specially designed questionnaire that was also given to a control group consisting of 194 consecutive patients who were seen in our outpatient clinic and had suffered IS at least 6 months previously.
The prevalence of acute infection in the study group was significantly higher (44/182 = 24.2%) than in the control group (19/194 = 9.7%; odds ratio, 2.93; 95% confidence interval, 1.64 to 5.26; P = .0002) and infection occurred mostly within 1 week before the IS (41/44). Neither the severity of the IS nor the type of the infection was significantly different in patients and control subjects.
Acute infections of different types constitute a risk factor for IS, particularly within 1 week of the event. However, the severity of the stroke is not related to this factor.
To characterize the risk factors for stroke in children and their relationship to outcomes.
We reviewed charts of children with ischemic and hemorrhagic stroke seen at Hopital Sainte-Justine, Montreal between 1991 and 1997.
We found 51 ischemic strokes: 46 arterial and 5 sinovenous thromboses. Risk factors were variable and multiple in 12 (24%) of the 51 ischemic strokes. Ischemic stroke recurred in 3 (8%) patients with a single or no identified risk factor and in 5 (42%) of 12 patients with multiple risk factors (p = 0.01). We also found 21 hemorrhagic strokes, 14 (67%) of which were caused by vascular abnormalities. No patient with hemorrhagic stroke had multiple risk factors. Hemorrhagic stroke recurred in two patients (10%). Outcome in all 72 stroke patients was as follows: asymptomatic, 36%; symptomatic epilepsy or persistent neurologic deficit, 45%; and death, 20%. Death occurred more frequently in patients with recurrent stroke (40%) than in those with nonrecurrent stroke (16%).
Multiple risk factors are found in many ischemic strokes and may predict stroke recurrence. Recurrent stroke tends to increase rate of mortality. Because of the high prevalence and importance of multiple risk factors, a complete investigation, including hematologic and metabolic studies and angiography, should be considered in every child with ischemic stroke, even when a cause is known.
Ischemic stroke during infancy and childhood has the potential for life-long morbidity. Information on the neurologic outcome of children who survive ischemic stroke is lacking. Children surviving ischemic stroke between January 1, 1995 and July 1, 1999 were prospectively followed. Neurologic deficit severity was based on the Pediatric Stroke Outcome Measure (PSOM) developed in this study and parental response to two recovery questions. Predictor variables for poor outcome were tested. One-hundred twenty-three children with arterial ischemic stroke and 38 with sinovenous thrombosis were followed for a mean of 2.1 years (range, 0.8 to 6.6 years). The primary outcome based on PSOM assessment was: normal, 37%; mild deficit, 20%; moderate deficit, 26%; and severe deficit, 16%. The secondary outcome was full recovery in 45% of patients, based on parental response. The primary and secondary outcome measures were moderately correlated (P < .001; K = 0.5). In bivariate analysis, arterial stroke type, male gender, age of at least 28 days, presence of associated neurologic disorders, and need for rehabilitation therapy after stroke were predictors of poor outcome (P < .05). Multivariate analysis showed that only arterial ischemic stroke, associated neurologic disorders, and presence of rehabilitation therapy were independent predictors of poor outcome (P < .02). Poor outcome in children after ischemic stroke is therefore frequent and more likely in the presence of arterial stroke, rehabilitation therapy, and associated neurologic disorders, which justifies clinical trials of treatment strategies in childhood ischemic stroke.
Little is known about long-term physical sequelae, cognitive functioning, and quality of life in children who have experienced ischemic stroke. Thirty-seven patients under 16 years of age were studied; the median interval after stroke was 7 years. CT-scans were reassessed to determine the type of infarction at baseline. Occurrences of death, of new cardiovascular events, and of seizures during follow-up were recorded. Surviving patients were invited for a follow-up examination, including physical check-up, global screening of cognition, and an inventory of subjective health perception. Only two patients were lost to follow-up. During follow-up four died, nine developed seizures, eight had transient ischemic attacks, and two experienced a recurrent ischemic stroke. None of the patients had cardiac complications during follow-up. In 11 of 27, no functional impairment was found, in 15 there was a hemiparesis of varying severity, and in one a paraplegia. There was a significant shift in cognitive functioning towards lower levels, especially in children with epilepsy. Remedial teaching was frequently needed. Many of the parents' perceived their child's behavior to be very changeable. Three-quarters of the children considered themselves as healthy as other children, and almost all of them as happy. The physical and functional prognosis after ischemic stroke in childhood is relatively good, particularly in children with no serious causative illness, but special education is often needed and social changes occur.
Upper respiratory tract illnesses have been associated with an increased risk of ischemic heart disease and stroke. During two influenza seasons, we assessed the influence of vaccination against influenza on the risk of hospitalization for heart disease and stroke, hospitalization for pneumonia and influenza, and death from all causes.
Cohorts of community-dwelling members of three large managed-care organizations who were at least 65 years old were studied during the 1998-1999 and 1999-2000 influenza seasons. Administrative and clinical data were used to evaluate outcomes, with multivariable logistic regression to control for base-line demographic and health characteristics of the subjects.
There were 140,055 subjects in the 1998-1999 cohort and 146,328 in the 1999-2000 cohort, of which 55.5 percent and 59.7 percent, respectively, were immunized. At base line, vaccinated subjects were on average sicker, having higher rates of most coexisting conditions, outpatient care, and prior hospitalization for pneumonia than unvaccinated subjects. Unvaccinated subjects, however, were more likely to have been given a prior diagnosis of dementia or stroke. Vaccination against influenza was associated with a reduction in the risk of hospitalization for cardiac disease (reduction of 19 percent during both seasons [P<0.001]), cerebrovascular disease (reduction of 16 percent during the 1998-1999 season [P<0.018] and 23 percent during the 1999-2000 season [P<0.001]), and pneumonia or influenza (reduction of 32 percent during the 1998-1999 season [P<0.001] and 29 percent during the 1999-2000 season [P<0.001]) and a reduction in the risk of death from all causes (reduction of 48 percent during the 1998-1999 season [P<0.001] and 50 percent during the 1999-2000 season [P<0.001]). In analyses according to age, the presence or absence of major medical conditions at base line, and study site, the findings were consistent across all subgroups.
In the elderly, vaccination against influenza is associated with reductions in the risk of hospitalization for heart disease, cerebrovascular disease, and pneumonia or influenza as well as the risk of death from all causes during influenza seasons. These findings highlight the benefits of vaccination and support efforts to increase the rates of vaccination among the elderly.
Phenylpropanolamine (PPA) and pseudoephedrine are sympathomimetics contained in over-the-counter cold preparations. A case-control study linked PPA use with hemorrhagic stroke in women. Twenty-two patients with stroke associated with use of these drugs are described.
In a consecutive stroke registry since 1988, 22 patients had stroke associated with over-the-counter sympathomimetics. Sympathomimetic dosage and type, time interval until stroke onset, and neuroimaging findings are described.
Ten male and 12 female patients were included. Intracerebral hemorrhage occurred in 17 patients, subarachnoid hemorrhage in 4, and ischemic stroke in 1. Stroke was associated with PPA use in 16 patients (dose 75 to 675 mg), with pseudoephedrine in 4 (dose 60 to 300 mg), and with others administered by the nasal route in 2 (oxymetazoline and phenylephrine). Stroke occurred after a single dose in 17 patients and after daily use during several days in 5. The interval between drug exposure and clinical onset varied from 30 minutes to 24 hours. Stroke occurred after recommended doses of PPA (50 to 75 mg) in 32% and pseudoephedrine (60 mg) in 50% of patients. Eight patients had acute hypertension at stroke onset. Cerebral angiography was normal in 8 cases and showed diffuse vasospasm or beading in 10 patients.
Stroke related to over-the-counter sympathomimetics was associated with acute hypertension and/or vasospasm or angiitis mechanisms, most related to the use of PPA; however, stroke also occurred with the use of other sympathomimetics, particularly pseudoephedrine. Although stroke complications occurred when doses were used that were higher than recommended doses, apparently there is also a stroke risk when these agents are taken properly.
Using a California-wide hospital discharge database, the authors analyzed all first admissions for stroke in children 1 month through 19 years of age from 1991 through 2000. Incidence rates were estimated as the number of first hospitalizations divided by the person-years at risk; case fatality rates were based on in-hospital deaths.
The authors identified 2,278 first admissions for childhood stroke, yielding an annual incidence rate of 2.3 per 100,000 children (1.2 for ischemic stroke, 1.1 for hemorrhagic stroke). Compared with whites, black children were at higher risk of stroke (for ischemic stroke, relative risk [RR] 2.59, 95% CI 2.17 to 3.09, p < 0.0001; subarachnoid hemorrhage [SAH], RR 1.59, CI 1.06 to 2.33, p = 0.02; intracerebral hemorrhage [ICH], RR 1.66, CI 1.23 to 2.13, p = 0.0001). Hispanics, however, had a lower risk of ischemic stroke (RR 0.70, CI 0.60 to 0.82, p < 0.0001) and ICH (RR 0.77, CI 0.64 to 0.93, p = 0.0004), whereas Asians had similar risks as whites. Boys were at higher risk for all stroke types than girls (ischemic stroke, RR 1.25, CI 1.11 to 1.40, p = 0.0002; SAH, RR 1.24, CI 1.00 to 1.53, p = 0.047; ICH, RR 1.34, CI 1.16 to 1.56, p = 0.0001). After eliminating cases with coexisting sickle cell disease, excess stroke risk persisted in blacks; after elimination of trauma, excess stroke risk persisted in boys. Case fatality rates were similar among different ethnic groups. Compared with girls, boys had a higher case fatality rate for ischemic stroke (17 vs 12%; p = 0.002) but not for ICH or SAH.
Rates of hospitalization for stroke are higher among black children and boys; sickle cell disease and trauma do not fully account for these findings.
The impact of influenza vaccination on major cause-specific hospitalization and the duration of hospital stay is rarely reported. Our purpose was to study the effect of vaccine efficacy on major disease-specific hospitalization and the duration of hospital stays among elderly persons.
From 1 January through 30 June 2001, we prospectively observed 35,637 vaccinated elderly persons (age, >or=65 years) and 53,094 unvaccinated elderly persons in Kaohsiung County, Taiwan, by computerized linkage to the National Health Insurance database. Of these persons, 21,347 had been assigned a high-risk status by the Department of Health, Taiwan. Univariate and multivariate logistic regression were used for determining vaccine efficacy in hospitalization. Multiple linear regression analyses were performed for determining the length of hospital stays.
In both high-risk and low-risk groups, vaccination was associated with reducing the rates of hospitalization for all causes (20% vs. 23%), lung diseases, congestive heart failure (43% vs. 32%), renal disease, and liver disease (P<.05). It was also significant for stroke, hypertension, diabetes, neoplasm, and injury in low-risk patients (P<.05). Multivariate logistic regression showed that vaccination was significantly associated with reducing the rate of hospitalization (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.86-0.92), but those with high-risk status had an increased risk of hospitalization (OR, 3.69; 95% CI, 3.56-3.82). Multiple linear regression analysis showed that vaccination decreased the duration of all-cause hospital stays (coefficient, -2.4 days; 95% CI, -2.7 to -2.1 days) and of hospitalization due to lung disease (coefficient, -4.9 days; 95% CI, -6.0 to -3.8 days).
Influenza vaccination may reduce hospitalization rates and shorten hospital stays not only for lung diseases but also for other common diseases in high-risk and low-risk elderly populations.
There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events.
We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients.
A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events.
Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events.
A recent study reported that mortality from stroke in children and adolescents decreased by 58% from 1979 to 1998, although it wasn't clear if the case fatality or the incidence of stroke in this age group is decreasing. We report trends of stroke incidence and case fatality in children and adolescents within a large biracial population. The study involved collection of all strokes in the study population between January 1, 1988 and December 31, 1989, July 1, 1993 and June 30, 1994, and January 1, 1999 and December 31, 1999, at all of the regional hospitals serving the Greater Cincinnati/Northern Kentucky population (only the children's hospital in 1988). Study nurses reviewed the medical records of all inpatients with stroke-related discharge diagnoses and abstracted relevant data. A study physician reviewed each abstract to determine whether a stroke or transient ischemic attack had occurred. A total of 54 strokes occurred in children or adolescents younger than 20 years during the three study periods (30% African American, 70% Caucasian, and 56% female). The overall incidence rate of all strokes in children younger than 15 years was 6.4/100,000 in 1999, a nonsignificant increase when compared to 1988. The 30-day case-fatality rates were 18% in 1988-1989, 9% in 1993-1994, and 9% in 1999. We found that the incidence of strokes in children has been stable over the past 10 years. The previously reported nationwide decrease in overall stroke mortality in children might be due to decreasing case fatality after stroke and not decreasing stroke incidence. Based on our data, we conservatively estimated that approximately 3000 children less than 20 years old would have a stroke in the United States in 2004.
The relation between acute ischaemic stroke and infection is complex. Infection appears to be an important trigger that precedes up to a third of ischaemic strokes and can bring about stroke through a range of potential mechanisms. Infections that present subsequent to stroke also complicate up to a third of cases of stroke and might worsen outcome. Inflammatory responses, which are a defence mechanism against infection but can also be a pathogenic mechanism that precipitates stroke and neurological sequelae, are important features. Although factors such as stroke severity and dysphagia are important predictors of poststroke infection, there is evidence from experimental and clinical settings of impaired immunity or brain-induced immunodepression after stroke. Greater understanding of the relation between inflammation and both infection and ischaemic mechanisms is needed. This might be particularly important because new treatment strategies for acute ischaemic stroke are being investigated, including those that modulate cytokines and the immune system.
Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients
- J Syrjanen
- V V Valtonen
- M Livanainen
- M Kaste
- J K Huttunen
Syrjanen J, Valtonen VV, Livanainen M, Kaste M,
Huttunen JK. Preceding infection as an important risk
factor for ischaemic brain infarction in young and middle
aged patients. Br Med J 1988;296:1156-1160.
- Syrjanen