Publications by authors named "Christine K Fox"

32 Publications

Factors associated with seizures at initial presentation in pediatric patients with cerebral arteriovenous malformations.

J Neurosurg Pediatr 2021 Sep 24:1-6. Epub 2021 Sep 24.

1Department of Neurological Surgery, University of California San Francisco, San Francisco.

Objective: Children with cerebral arteriovenous malformations (AVMs) can present with seizures, potentially increasing morbidity and impacting clinical management. However, the factors that lead to seizures as a presenting sign are not well defined. While AVM-related seizures have been described in case series, most studies have focused on adults and have included patients who developed seizures after an AVM rupture. To address this, the authors sought to analyze demographic and morphological characteristics of AVMs in a large cohort of children.

Methods: The demographic, clinical, and AVM morphological characteristics of 189 pediatric patients from a single-center database were studied. Univariate and multivariate logistic regression models were used to test the effect of these characteristics on seizures as an initial presenting symptom in patients with unruptured brain AVMs.

Results: Overall, 28 of 189 patients initially presented with seizures (14.8%). By univariate comparison, frontal lobe location (p = 0.02), larger AVM size (p = 0.003), older patient age (p = 0.04), and the Supplemented Spetzler-Martin (Supp-SM) grade (0.0006) were associated with seizure presentation. Multivariate analysis confirmed an independent effect of frontal lobe AVM location and higher Supp-SM grade. All patients presenting with seizures had AVMs in the cortex or subcortical white matter.

Conclusions: While children and adults share some risk factors for seizure presentation, their risk factor profiles do not entirely overlap. Pediatric patients with cortical AVMs in the frontal lobe were more likely to present with seizures. Additionally, the Supp-SM grade was highly associated with seizure presentation. Future clinical research should focus on the effect of therapeutic interventions targeting AVMs on seizure control in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.6.PEDS21126DOI Listing
September 2021

Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.

Mol Genet Genomic Med 2021 Sep 7:e1794. Epub 2021 Sep 7.

Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

Background: To investigate whether common variants in EPHB4 and RASA1 are associated with cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts.

Methods: Familial CCM cases enrolled in the Brain Vascular Malformation Consortium were included (n = 338). Total lesions and large lesions (≥5 mm) were counted on MRI; clinical history of ICH at enrollment was assessed by medical records. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We tested the association of seven common variants (three in EPHB4 and four in RASA1) using multivariable logistic regression for ICH (odds ratio, OR) and multivariable linear regression for total and large lesion counts (proportional increase, PI), adjusting for age, sex, and three principal components. Significance was based on Bonferroni adjustment for multiple comparisons (0.05/7 variants = 0.007).

Results: EPHB4 variants were not significantly associated with CCM severity phenotypes. One RASA1 intronic variant (rs72783711 A>C) was significantly associated with ICH (OR = 1.82, 95% CI = 1.21-2.37, p = 0.004) and nominally associated with large lesion count (PI = 1.17, 95% CI = 1.03-1.32, p = 0.02).

Conclusion: A common RASA1 variant may be associated with ICH and large lesion count in familial CCM. EPHB4 variants were not associated with any of the three CCM severity phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1794DOI Listing
September 2021

Long-Term Risk of Epilepsy After Pediatric Stroke and Potential Genetic Vulnerabilities.

Stroke 2021 Nov 2;52(11):3541-3542. Epub 2021 Sep 2.

Departments of Neurology and Pediatrics (C.K.F.), University of California San Francisco.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.121.036376DOI Listing
November 2021

Pediatric moyamoya MRI score: an imaging-based scale to predict outcomes in surgically treated pediatric patients with moyamoya.

Neurosurg Focus 2021 09;51(3):E8

2Department of Radiology and Biomedical Imaging, University of California, San Francisco.

Objective: Moyamoya is a progressive arteriopathy that predisposes patients to stroke due to stenosis of the intracranial internal carotid arteries and their proximal branches. Despite the morbidity caused by this condition, the ability to accurately predict prognosis for individual patients remains challenging. The goal of this study was to develop a systematic scoring method based on parenchymal findings on preoperative brain MRI to predict long-term outcomes for surgically treated pediatric patients with moyamoya.

Methods: A retrospective surgical cohort of pediatric patients (≤ 18 years of age at the time of the initial surgery) with moyamoya from a single center were studied. Radiological variables with existing correlations between outcomes in moyamoya or other vascular diseases were chosen to score preoperative MRI based on easily defined parenchymal findings that could be rapidly assessed and used to make a numeric score. Calculated scores were correlated with clinical outcome measures using the Pearson correlation coefficient and area under the receiver operating characteristic curve (AUROC).

Results: A total of 35 children with moyamoya disease or moyamoya syndrome were included in the study, with a median follow-up time of 2.6 years from the time of surgery. The pediatric moyamoya MRI score (PMMS) consists of ischemic changes (0-2; 0 = none, 1 = focal, 2 = diffuse), encephalomalacia (0-2; 0 = none, 1 = focal, 2 = diffuse), and hemorrhage (0-1; 0 = not present, 1 = present). PMMSs were highly correlated with pediatric modified Rankin Scale scores at the last follow-up (r = 0.7, 95% CI 0.44-0.84; p < 0.001) as a six-point scale, and when dichotomized (AUROC = 0.85).

Conclusions: The PMMS was found to be a simple tool based on preoperative MRI data that could be quickly and easily calculated and correlated with disability. This scoring method may aid future development of predictive models of outcomes for children with moyamoya disease and moyamoya syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2021.6.FOCUS21283DOI Listing
September 2021

Seizure Incidence Rates in Children and Adults With Familial Cerebral Cavernous Malformations.

Neurology 2021 Aug 13. Epub 2021 Aug 13.

Center for Cerebrovascular Research, University of California San Francisco, San Francisco, CA, USA.

Background And Objectives: Seizure incidence rates related to Familial Cerebral Cavernous Malformation (FCCM) are not well described, especially for children. To measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity, we studied a cohort of children and adults with FCCM enrolled in the Brain Vascular Malformation Consortium (BVMC).

Methods: Seizure data were collected from participants with FCCM in the BVMC at enrollment and during follow-up. We estimated seizure probability by age, and tested whether cerebral cavernous malformation (CCM) counts or genotype were associated with earlier seizure onset.

Results: The study cohort included 479 FCCM cases. Median age at enrollment was 42.5 years (Interquartile Range [IQR] 22.5-55.0) and 19% were children (<18 years old). Median large CCM count was 3 (IQR: 1-5). Among 393 with genotyping, mutations were: CCM1-Common Hispanic Mutations (88%), another CCM1 mutation (5%), CCM2 mutations (5%), and CCM3 mutations (2%). Prior to or during the study, 202 (42%) had a seizure. The cumulative incidence of a childhood seizure was 20.3% (95% CI 17.0 - 23.4) and by age 80 years was 60.4% (95% CI 54.2-65.7). More total CCMs (Hazard Ratio [HR] 1.24 per SD unit increase, 95% CI 1.1 - 1.4) or more large CCMs (HR=1.5 per SD unit increase, 95% CI 1.2-1.9) than expected for age and sex increased seizure risk. A CCM3 mutation also increased risk compared to other mutations (HR 3.11, 95% CI 1.15-8.45). Individuals with a seizure prior to enrollment had increased hospitalization rates during follow-up (Incidence Rate Ratio 10.9, 95% CI 2.41 - 49.32) compared to patients without a seizure history.

Discussion: Individuals with FCCM have a high seizure incidence, and those with more CCMs or CCM3 genotype are at greater risk. Seizures increase health care utilization in FCCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480481PMC
August 2021

Modified Pediatric ASPECTS: Building Tools for Future Pediatric Stroke Studies.

Neurology 2021 Aug 13. Epub 2021 Aug 13.

Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012543DOI Listing
August 2021

Multiple Tumor-Associated Intracranial Aneurysms Adjacent to a Suprasellar Germ Cell Tumor: Case Report and Review of Literature.

Pediatr Neurosurg 2021 28;56(5):482-491. Epub 2021 Jul 28.

Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.

Introduction: Tumor-associated intracranial aneurysms are rare and not well understood.

Case Presentation: We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms.

Discussion: We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000517890DOI Listing
July 2021

Pediatric Ischemic Stroke: An Infrequent Complication of SARS-CoV-2.

Ann Neurol 2021 04 28;89(4):657-665. Epub 2021 Jan 28.

Division of Neurology, Department of Paediatrics, and Child Health Evaluative Sciences Program, The Hospital for Sick Children, Toronto, ON, Canada.

Objective: Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS-CoV-2 is unknown. This study aimed to determine the proportion of pediatric SARS-CoV-2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS-CoV-2 in the first 3 months of the pandemic in an international cohort.

Methods: We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS-CoV-2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS-CoV-2 from March 1 to May 31, 2020.

Results: Of 42 centers with SARS-CoV-2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS-CoV-2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS-CoV-2. Seven of 8 patients with SARS-CoV-2 had additional established stroke risk factors.

Interpretation: As in adults, pediatric stroke is an infrequent complication of SARS-CoV-2, and SARS-CoV-2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS-CoV-2 in pediatric stroke better, SARS-CoV-2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657-665.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25991DOI Listing
April 2021

Clinical outcomes after revascularization for pediatric moyamoya disease and syndrome: A single-center series.

J Clin Neurosci 2020 Sep 19;79:137-143. Epub 2020 Aug 19.

Departments of Neurology and Pediatrics, University of California, San Francisco, CA, USA. Electronic address:

Moyamoya is a progressive cerebrovascular arteriopathy that affects children of any age. The goal of this study was to determine imaging and clinical outcomes as well as complication rates in a pediatric cohort undergoing either a combined direct/indirect or indirect-only revascularization approach. Patients with moyamoya disease or syndrome ≤ 18 years of age at the time of initial surgery were identified, and clinical data were collected retrospectively. Over a 12-year period, 26 patients underwent revascularization procedures on 49 hemispheres with a median follow-up of 2.6 years from surgery. Median age at surgery was 7.3 years (range 1.4-18.0 years). Thirty-three hemispheres (67.3%) underwent combined revascularization with a direct bypass and encephalomyosynangiosis, and sixteen hemispheres (32.7%) underwent indirect-only revascularization. The rate of 30-day perioperative complication was 10.2%, and the rate of postoperative clinical stroke by end of follow-up was 10.2% by hemisphere. There was a 5.7% rate of intraoperative bypass failure requiring conversion to an indirect revascularization approach. On follow-up imaging, 96.9% of direct bypasses remained patent. On multivariate analysis, higher preoperative Pediatric Stroke Outcome Measure (PSOM) scores were associated with lower rates of good clinical outcome on follow-up (unit OR 0.03; p = 0.03). Patients with age < 5.4 years had lower rates of good clinical outcome on follow-up. In this North American cohort, both combined direct/indirect and indirect only revascularization techniques were feasible. However, younger children < 5.4 years of age have worse outcomes than older children, similar to east Asian cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2020.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573194PMC
September 2020

Single-center series of boys with recurrent strokes and rotational vertebral arteriopathy.

Neurology 2020 09 20;95(13):e1830-e1834. Epub 2020 Jul 20.

From the Departments of Neurology (C.K.F., H.J.F.), Pediatrics (C.K.F., H.J.F., K.I.A., N.G.), Radiology and Biomedical Imaging (S.W.H., V.V.H.), and Neurological Surgery (K.I.A., M.T.L., N.G.), University of California San Francisco; and Department of Neurological Surgery (M.T.L.), Barrow Neurological Institute, Phoenix, AZ.

Objective: To describe a pediatric stroke syndrome with chronic focal vertebral arteriopathy adjacent to cervical abnormalities.

Methods: At a single pediatric stroke center, we identified consecutive children with stroke and vertebral arteriopathy of the V3 segment with adjacent cervical bony or soft tissue abnormalities. We abstracted clinical presentation, treatment, and follow-up data from medical charts.

Results: From 2005 to 2019, 10 children (all boys, ages 6-16 years) presented with posterior circulation strokes and vertebral arteriopathy with adjacent cervical pathology. Two children had bony abnormalities: one had a congenital arcuate foramen and one had os odontoideum with cervical instability. In children without bony pathology, vertebral artery narrowing during contralateral head rotation was visualized by digital subtraction angiography. Eight boys had recurrent ischemic events despite anti-thrombotic treatment (including 5 with multiple recurrences) and were treated surgically to prevent additional stroke. Procedures included vertebral artery decompression (n = 6), endovascular stent and spinal fusion (n = 1), and vertebral artery endovascular occlusion (n = 1). In boys treated with decompression, cervical soft tissue abnormalities (ruptured atlantoaxial bursa, ruptured joint capsule, or connective tissue scarring) were directly visualized during open surgery. No other etiology for stroke or dissection was found in any of the cases. Two boys without recurrent stroke were treated with activity restriction and antithrombotics. At a median follow-up of 51 months (range 17-84), there have been no additional recurrences.

Conclusions: Children with V3 segmental vertebral arteriopathy frequently have stroke recurrence despite antithrombotics. Cervical bone imaging and angiography with neck rotation can identify underlying pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000010416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682823PMC
September 2020

Bringing high-grade arteriovenous malformations under control: clinical outcomes following multimodality treatment in children.

J Neurosurg Pediatr 2020 Apr 10:1-10. Epub 2020 Apr 10.

Departments of1Neurological Surgery.

Objective: Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs.

Methods: A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram.

Results: The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year).

Conclusions: Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.1.PEDS19487DOI Listing
April 2020

Validation of the pediatric stroke outcome measure for classifying overall neurological deficit.

Pediatr Res 2020 08 16;88(2):234-242. Epub 2020 Mar 16.

Department of Pediatrics, Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada.

Background: The pediatric stroke outcome measure (PSOM) is a standardized, disease-specific outcome measure. We aimed to validate the overall classification of neurological deficit severity using PSOM.

Methods: We identified 367 neonates/children with arterial ischemic stroke (AIS) (Derivation Cohort). We analyzed the PSOM subscales (scored as 0 [no deficit], 0.5 [minimal/mild deficit; normal function], 1 [moderate deficit; slowing function], or 2 [severe deficit; missing function]) to derive severity levels using latent class analysis (LCA). We validated a severity classification scheme (PSOM-SCS) in: (a) children who had Pediatric Evaluation of Disability Inventory (PEDI; n = 63) and/or the Pediatric Quality-of-Life Inventory (PedsQL; n = 97) scored; and (b) an external cohort (AIS; n = 102) with concurrently scored modified Rankin Scale (mRS), King's Outcome Scale for Childhood Head-Injury (KOSCHI) and PSOM.

Results: Within the Derivation Cohort, LCA identified three severity levels: "normal/mild," "moderate," and "severe" (83.7%, 13.3%, and 3%, respectively). We developed severity classification based on PSOM subscale scores: "normal/mild"-normal function in all domains or slowing in one domain, "moderate"-slowing in ≥2 domains or missing function in one domain, and "severe"-missing function in ≥2 domains or slowing in ≥1 plus missing in one domain. PEDI and PedsQL both differed significantly across the severity groups. PSOM-SCS displayed high concordance with mRS (agreement coefficient [AC2] = 0.88) and KOSCHI (AC2 = 0.79).

Conclusion: The PSOM-SCS constitutes a valid tool for classifying overall neurological severity emphasizing function and encompassing the full range of severity in pediatric stroke.

Impact: Arithmetic summing of the PSOM subscales scores to assess severity classification is inadequate.The prior severity classification using PSOM overestimates poor outcomes.Three distinct severity profiles using PSOM subscales are identified.The PSOM-SCS is in moderate to excellent agreement with other disability measures.PSOM-SCS offers a valid tool for classifying the overall neurological deficit severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-020-0842-5DOI Listing
August 2020

Review on the Diagnosis and Treatment of Reversible Cerebral Vasoconstriction Syndrome in Children and Adolescents.

Semin Neurol 2020 06 20;40(3):294-302. Epub 2020 Feb 20.

Division of Neurology, Department of Pediatrics, University of California San Francisco, San Francisco, California.

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiologic diagnosis that affects children and adolescents, but it is much more frequently reported in adults. Clinically, patients present with severe and commonly recurrent thunderclap headaches. Typical precipitating triggers include vasoactive substances, serotonergic agents, and the postpartum period. There may be associated neurologic complications at presentation or in the weeks following, such as convexity subarachnoid hemorrhage, stroke, cerebral edema, cervical artery dissection (CeAD), and seizures. Angiographically, the cerebral arteries demonstrate segmental vasoconstriction and dilation, although imaging early in the clinical course may be normal. Work-up is performed to exclude intracranial disorders such as vasculitis, subarachnoid hemorrhage due to ruptured aneurysm, meningitis, and intracranial venous sinus thrombosis. Within 1 month of initial symptom onset, clinical symptoms such as severe headache have ceased, and within 3 months, the cerebral vasoconstriction is much improved or resolved. Management involves avoidance of precipitating triggers and potentially short-term pharmacotherapy with calcium channel blockers for patients with associated neurologic complications. Steroids are not recommended and may worsen the clinical outcome. Prognosis is excellent in the large majority of patients, and only 5% of patients experience a recurrence of RCVS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1702942DOI Listing
June 2020

Comparative study of posterior and anterior circulation stroke in childhood: Results from the International Pediatric Stroke Study.

Neurology 2020 01 19;94(4):e337-e344. Epub 2019 Dec 19.

From the Neurovascular Research Group, Department of Neurology (B.G.S.), and Division of Child Neurology, Department of Pediatrics (B.G.S., M.S.), Inselspital Bern, University Hospital, University of Bern; Pediatric Neurology (B.G.S.), Institute of Pediatrics of Southern Switzerland, San Giovanni Hospital Bellinzona, Ente Ospedaliero Cantonale, Switzerland; Section of Pediatric Neurology, Department of Pediatrics and Child Health (M.F.R.), University of Manitoba, Children's Hospital Research Institute of Manitoba, Canada; Division of Neurology, Department of Pediatrics (M.C., W.D.L.), The Ohio State University and Nationwide Children's Hospital, Columbus; Division of Neurology (L.A.B., L.L.B.), Children's Hospital of Philadelphia; Departments of Neurology and Pediatrics (L.A.B., L.L.B.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Departments of Neurology and Pediatrics (C.K.F.), University of California, San Francisco; Unit of Clinical Epidemiology (A.P.), Ente Ospedaliero Cantonale, Bellinzona; Division of Pneumology (A.P.), University of Geneva, Switzerland; and Department of Neurology (M.T.M.), Royal Children's Hospital Melbourne, Murdoch Children's Research Institute Melbourne, Parkville, Victoria, Australia.

Objective: To compare risk factors, clinical presentation, and outcomes after posterior circulation arterial ischemic stroke (PCAIS) and anterior circulation arterial ischemic stroke (ACAIS) in neonates and children.

Methods: In this international multicenter observational study including neonates and children up to 18 years of age with arterial ischemic stroke (AIS), we compared clinical and radiologic features according to stroke location.

Results: Of 2,768 AIS cases, 507 (18%) were located in the posterior circulation, 1,931 (70%) in the anterior circulation, and 330 (12%) involved both. PCAIS was less frequent in neonates compared to children (8.8% vs 22%, < 0.001). Children with PCAIS were older than children with ACAIS (median age 7.8 [interquartile range (IQR) 3.1-14] vs 5.1 [IQR 1.5-12] years, < 0.001), and more often presented with headache (54% vs 32%, < 0.001) and a lower Pediatric NIH Stroke Scale score (4 [IQR 2-8] vs 8 [IQR 3-13], = 0.001). Cervicocephalic artery dissections (CCAD) were more frequent (20% vs 8.5%, < 0.001), while cardioembolic strokes were less frequent (19% vs 32%, < 0.001) in PCAIS. Case fatality rates were equal in both groups (2.9%). PCAIS survivors had a better outcome (normal neurologic examination at hospital discharge in 29% vs 21%, = 0.002) than ACAIS survivors, although this trend was only observed in children and not in neonates.

Conclusion: PCAIS is less common than ACAIS in both neonates and children. Children with PCAIS are older and have a higher rate of CCAD, lower clinical stroke severity, and better outcome than children with ACAIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000008837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978473PMC
January 2020

Arterial Ischemic Stroke Secondary to Cardiac Disease in Neonates and Children.

Pediatr Neurol 2019 11 27;100:35-41. Epub 2019 Jun 27.

Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, California.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2019.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034952PMC
November 2019

Arteriopathy Influences Pediatric Ischemic Stroke Presentation, but Sickle Cell Disease Influences Stroke Management.

Stroke 2019 05;50(5):1089-1094

Departments of Pediatrics, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas and Children's Health Dallas (M.M.D.).

Background and Purpose- Sickle cell disease (SCD) and arteriopathy are pediatric stroke risk factors that are not mutually exclusive. The relative contributions of sickled red blood cells and arteriopathy to stroke risk are unknown, resulting in unclear guidelines for primary and secondary stroke prevention when both risk factors are present. We hypothesized that despite similarities in clinical presentation and radiographic appearance of arteriopathies, stroke evaluation and management differ in children with SCD compared with those without SCD. Methods- We compared presentation and management of children with and without SCD enrolled in the IPSS (International Pediatric Stroke Study) with acute arterial ischemic stroke, according to SCD and arteriopathy status. Regression modeling determined relative contribution of SCD and arteriopathy in variables with significant frequency differences. Results- Among 930 childhood arterial ischemic strokes, there were 98 children with SCD, 67 of whom had arteriopathy, and 466 without SCD, 392 of whom had arteriopathy. Arteriopathy, regardless of SCD status, increased likelihood of hemiparesis (odds ratio [OR], 1.94; 95% CI, 1.46-2.56) and speech abnormalities (OR, 1.67; 95% CI, 1.29-2.19). Arteriopathy also increased likelihood of headache but only among those without SCD (OR, 1.89; 95% CI, 1.40-2.55). Echocardiograms were less frequently obtained in children with SCD (OR, 0.58; 95% CI, 0.37-0.93), but the frequency of identified cardiac abnormalities was similar in both groups ( P=0.57). Children with SCD were less likely to receive antithrombotic therapy, even in the presence of arteriopathy (OR, 0.14; 95% CI, 0.08-0.22). Arteriopathy was associated with a significantly higher likelihood of antithrombotic therapy in children without SCD (OR, 5.36; 95% CI, 3.55-8.09). Conclusions- Arteriopathy, and not SCD status, was most influential of stroke presentation. However, SCD status influenced stroke management because children with SCD were less likely to have echocardiograms or receive antithrombotic therapy. Further work is needed to determine whether management differences are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.118.022800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481313PMC
May 2019

Socioeconomic determinants of outcome after childhood arterial ischemic stroke.

Neurology 2018 08 6;91(6):e509-e516. Epub 2018 Jul 6.

From the Department of Pediatrics (L.C.J.), Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, TN; Departments of Neurology (N.K.H., C.K.F., H.J.F.), Biostatistics and Epidemiology (N.K.H.), and Pediatrics (C.K.F., H.J.F.), University of California San Francisco; Department of Neurology (R.N.I.), The Children's Hospital of Philadelphia, PA; Department of Neurology (P.P.), Children's National Medical Center, Washington, DC; Department of Neurology (G.A.d.V.), Hospital for Sick Children, Toronto, Ontario, Canada; and Department of Neurology (W.L.), Nationwide Children's Hospital, Columbus, OH.

Objective: To determine whether lower socioeconomic status (SES) is associated with worse 1-year neurologic outcomes and reduced access to rehabilitation services in children with arterial ischemic stroke (AIS).

Methods: From 2010 to 2014, the Vascular effects of Infection in Pediatric Stroke (VIPS) observational study prospectively enrolled and confirmed 355 children (age 29 days-18 years) with AIS at 37 international centers. SES markers measured via parental interview included annual household income (US dollars) at the time of enrollment, maternal education level, and rural/suburban/urban residence. Receipt of rehabilitation services was measured by parental report. Pediatric Stroke Outcome Measure scores were categorized as 0 to 1, 1.5 to 3, 3.5 to 6, and 6.5 to 10. Univariate and multivariable ordinal logistic regression models examined potential predictors of outcome.

Results: At 12 ± 3 months after stroke, 320 children had documented outcome measurements, including 15 who had died. In univariate analysis, very low income (
Conclusions: In a large, multinational, prospective cohort of children with AIS, low income was associated with worse neurologic outcomes compared to higher income levels. This difference was not explained by stroke type, neurologic comorbidities, or reported use of rehabilitation services. The root causes of this disparity are not clear and warrant further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000005946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105045PMC
August 2018

Children with post-stroke epilepsy have poorer outcomes one year after stroke.

Int J Stroke 2018 10 29;13(8):820-823. Epub 2018 Jun 29.

6 Neurology Division, Department of Pediatrics, Hospital for Sick Children, University of Toronto, ON, Canada.

Background Epilepsy is a common complication of pediatric stroke. Aim In this study, we aim to measure the association between epilepsy and neurologic outcome after childhood arterial ischemic stroke. Methods Prospective cohort study of children (29 days-19 years) enrolled after an acute arterial ischemic stroke at 21 international pediatric stroke centers and followed to identify epilepsy. One year post-stroke, outcomes were scored using the examination-based Pediatric Stroke Outcome Measure (range = 0-10); higher values reflect greater disability. Ordinal logistic regression was used to measure the association of Pediatric Stroke Outcome Measure scores (categorized as 0-1, 1.5-3, 3.5-6, 6.5-10) with epilepsy. Results Investigators enrolled 86 children (median age = 6.1 years, interquartile range (IQR) = 1.4-12.2 years) with acute stroke. At 1 year, 18/80 (23%) remained on an anticonvulsant including 8/80 (10%) with epilepsy. Among the 70 with Pediatric Stroke Outcome Measure scored, the median was 0.5 (IQR = 0-1.5) for children without epilepsy ( n = 63), and 6 (IQR = 0.5-10) for children with epilepsy ( n = 7). In univariable analyses, poorer 1-year outcome was associated with middle cerebral artery stroke, cortical infarcts, hemorrhagic transformation, hospital disposition not to home, and epilepsy. In multivariable analysis, middle cerebral artery stroke (odds ratio (OR) = 4.9, 95% confidence intervals (CI) = 1.1-21.3) and epilepsy (OR = 24.1, CI = 1.5-380) remained associated with poorer outcome. Conclusions Children who developed epilepsy during the first year post-stroke had poorer neurologic outcomes than those without epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493018784434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006892PMC
October 2018

Population-based study of ischemic stroke risk after trauma in children and young adults.

Neurology 2017 Dec 8;89(23):2310-2316. Epub 2017 Nov 8.

From the Departments of Neurology (C.K.F., A.L.N., H.J.F.), Pediatrics (C.K.F., A.L.N., H.J.F.), Epidemiology and Biostatistics (N.K.H.), and Surgery (R.A.D.), University of California, San Francisco; the Division of Research (D.R.V., S.S.), Kaiser Permanente Northern California, Oakland; and the Department of Emergency Medicine (D.R.V.), Kaiser Permanente Sacramento Medical Center, Sacramento, CA.

Objective: To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort.

Methods: We electronically identified trauma patients (<50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997-2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression.

Results: From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0-5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1-14.9) and neck (OR 5.6, CI 1.03-30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation).

Conclusions: Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000004708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719927PMC
December 2017

Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke: Correlates of Stroke Cause and Recurrence.

Stroke 2016 09 4;47(9):2221-8. Epub 2016 Aug 4.

From the Departments of Neurology (H.J.F., N.K.H., C.K.F.), Pediatrics (H.J.F., C.K.F.), and Biostatistics and Epidemiology (N.K.H.), University of California San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Pediatrics and Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX (M.M.D.); Children's Neuroscience Centre, Royal Children's Hospital, Parkville, Victoria, Australia (M.T.M.); Departments of Pediatrics and Clinical Neurosciences, University of Calgary, Alberta, Canada (A.K.); Department of Pediatrics, University of Alberta, Edmonton, Canada (J.Y.Y.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Departments of Pathology (E.A.H.) and Neurology (M.S.V.E.), Columbia University College of Physicians and Surgeons, New York, NY; Department of Epidemiology, Mailman School of Public Health, New York, NY (M.S.V.E.); and Department of Radiology, Stanford University, Palo Alto, CA (M.W.).

Background And Purpose: Among children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS.

Methods: In an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS.

Results: Median age at index stroke was 8.2 years (interquartile range, 3.6-14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3-10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of high-sensitivity C-reactive protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group, higher high-sensitivity C-reactive protein and serum amyloid A predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend toward higher high-sensitivity C-reactive protein and serum amyloid A, compared with children with stable or improved arteriopathies.

Conclusions: Among children with AIS, specific inflammatory biomarkers correlate with cause and-in the arteriopathy group-risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.116.013719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995134PMC
September 2016

Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk.

Dev Med Child Neurol 2017 Jan 16;59(1):38-44. Epub 2016 Jul 16.

Division of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Aim: To determine epilepsy risk factors after pediatric stroke.

Method: A cohort of children with arterial ischemic stroke (birth-18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression.

Results: Among 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1-year follow-up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7-13). Patients with more than 10 acute seizures had a 30-fold increased epilepsy risk (OR 30, 95% CI 2.9-305).

Interpretation: Pediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose-dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dmcn.13198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007772PMC
January 2017

Indirect and direct revascularization of ACTA2 cerebral arteriopathy: feasibility of the superficial temporal artery to anterior cerebral artery bypass with posterior auricular artery interposition graft: case report.

J Neurosurg Pediatr 2016 Sep 13;18(3):339-43. Epub 2016 May 13.

Departments of 1 Neurological Surgery.

Mutations in the smooth muscle-specific isoform of alpha actin (ACTA2) cause smooth muscle dysfunction in arteries. This rare loss-of-function mutation may cause a diffuse occlusive cerebral arteriopathy, resulting in stroke. While ACTA2 arteriopathy is often described as moyamoya-like, it has a distinct phenotype characterized by dilation of the proximal internal carotid artery (ICA) and occlusion of the terminal ICA and proximal middle cerebral artery. Intracranial arteries have an abnormally straight course, often with small aneurysms. There is limited experience with revascularization procedures for ACTA2 arteriopathy, and the safety and efficacy of these procedures are unknown. In this paper the authors present a symptomatic 6-year-old patient with ACTA2 cerebral arteriopathy who underwent both indirect revascularization and direct cerebrovascular bypass. Postoperatively, the patient suffered an ischemic infarct in a neighboring vascular territory. While direct cerebrovascular bypass is technically feasible, patients with ACTA2 arteriopathy may be at increased risk for perioperative stroke compared with patients with moyamoya disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2016.3.PEDS15694DOI Listing
September 2016

Neonatal seizures triple the risk of a remote seizure after perinatal ischemic stroke.

Neurology 2016 06 6;86(23):2179-86. Epub 2016 May 6.

From the Departments of Neurology (C.K.F., H.C.G., H.J.F.), Pediatrics (C.K.F., H.C.G., H.J.F.), and Epidemiology and Biostatistics (H.C.G.), University of California, San Francisco; the Division of Research (S.S.), Kaiser Permanente Northern California, Oakland; and the Division of Pediatric Neurology (S.E.S.), Kaiser Permanente Oakland Medical Center, CA.

Objectives: To determine incidence rates and risk factors of remote seizure after perinatal arterial ischemic stroke.

Methods: We retrospectively identified a population-based cohort of children with perinatal arterial ischemic stroke (presenting acutely or in a delayed fashion) from a large Northern Californian integrated health care system. We determined incidence and predictors of a remote seizure (unprovoked seizure after neonatal period, defined as 28 days of life) by survival analyses, and measured epilepsy severity in those with active epilepsy (≥1 remote seizure and maintenance anticonvulsant treatment) at last follow-up.

Results: Among 87 children with perinatal stroke, 40 (46%) had a seizure in the neonatal period. During a median follow-up of 7.1 years (interquartile range 3.2-10.5), 37 children had ≥1 remote seizure. Remote seizure risk was highest during the first year of life, with a 20% (95% confidence interval [CI] 13%-30%) cumulative incidence by 1 year of age, 46% (CI 35%-58%) by 5 years, and 54% (CI 41%-67%) by 10 years. Neonatal seizures increased the risk of a remote seizure (hazard ratio 2.8, CI 1.3-5.8). Children with neonatal seizures had a 69% (CI 48%-87%) cumulative incidence of remote seizure by age 10 years. Among the 24 children with active epilepsy at last follow-up, 8 (33%) were having monthly seizures despite an anticonvulsant and 7 (29%) were on more than one anticonvulsant.

Conclusions: Remote seizures and epilepsy, including medically refractory epilepsy, are common after perinatal stroke. Neonatal seizures are associated with nearly 3-fold increased remote seizure risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000002739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898314PMC
June 2016

Stroke in children with cardiac disease: report from the International Pediatric Stroke Study Group Symposium.

Pediatr Neurol 2015 Jan 5;52(1):5-15. Epub 2014 Oct 5.

Division of Pediatric Neurology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Background: Cardiac disease is a leading cause of stroke in children, yet limited data support the current stroke prevention and treatment recommendations. A multidisciplinary panel of clinicians was convened in February 2014 by the International Pediatric Stroke Study group to identify knowledge gaps and prioritize clinical research efforts for children with cardiac disease and stroke.

Results: Significant knowledge gaps exist, including a lack of data on stroke incidence, predictors, primary and secondary stroke prevention, hyperacute treatment, and outcome in children with cardiac disease. Commonly used diagnostic techniques including brain computed tomography and ultrasound have low rates of stroke detection, and diagnosis is frequently delayed. The challenges of research studies in this population include epidemiologic barriers to research such as small patient numbers, heterogeneity of cardiac disease, and coexistence of multiple risk factors. Based on stroke burden and study feasibility, studies involving mechanical circulatory support, single ventricle patients, early stroke detection strategies, and understanding secondary stroke risk factors and prevention are the highest research priorities over the next 5-10 years. The development of large-scale multicenter and multispecialty collaborative research is a critical next step. The designation of centers of expertise will assist in clinical care and research.

Conclusions: There is an urgent need for additional research to improve the quality of evidence in guideline recommendations for cardiogenic stroke in children. Although significant barriers to clinical research exist, multicenter and multispecialty collaboration is an important step toward advancing clinical care and research for children with cardiac disease and stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2014.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936915PMC
January 2015

Community-based case-control study of childhood stroke risk associated with congenital heart disease.

Stroke 2015 Feb 16;46(2):336-40. Epub 2014 Dec 16.

From the Departments of Neurology and Pediatrics, University of California, San Francisco (C.K.F., H.J.F.); and The Kaiser Permanente Northern California Division of Research, Oakland (S.S.).

Background And Purpose: A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke associated with CHD in a large community-based case-control study.

Methods: From 2.5 million children (aged <20 years) enrolled in a Northern California integrated healthcare plan, we identified children with ischemic and hemorrhagic strokes and randomly selected age- and facility-matched stroke-free controls (3 per case). We determined exposure to CHD (diagnosed before stroke) and used conditional logistic regression to analyze stroke risk factors.

Results: CHD was identified in 15 of 412 cases (4%) versus 7 of 1236 controls (0.6%). Cases of childhood stroke (occurring between ages 29 days to 20 years) with CHD had 19-fold (odds ratio, 19; 95% confidence interval 4.2-83) increased stroke risk compared to controls. History of CHD surgery was associated with >30-fold (odds ratio, 31; confidence interval 4-241) increased risk of stroke in children with CHD when compared with controls. After excluding perioperative strokes, the history of CHD surgery still increased the childhood stroke risk (odds ratio, 13; confidence interval 1.5-114). The majority of children with stroke and CHD were outpatients at the time of stroke, and almost half the cases who underwent cardiac surgery had their stroke >5 years after the most recent procedure. An estimated 7% of ischemic and 2% of hemorrhagic childhood strokes in the population were attributable to CHD.

Conclusions: CHD is an important childhood stroke risk factor. Children who undergo CHD surgery remain at elevated risk outside the perioperative period and would benefit from optimized long-term stroke prevention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.114.007218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308424PMC
February 2015

Arterial ischemic stroke in children: risk factors and etiologies.

Curr Neurol Neurosci Rep 2014 Jan;14(1):422

Division of Child Neurology, University of California, San Francisco, 675 Nelson Rising Lane, 402 B, San Francisco, CA, 94143, USA.

Stroke is increasingly recognized as a significant cause of morbidity and mortality in children, and as a financial burden for families and society. Recent studies have identified and confirmed presumptive risk factors, and have identified novel associations with childhood arterial ischemic stroke. A better understanding of risk factors for stroke in children, which differ from the atherosclerotic risk factors in adults, is the first step needed to improve strategies for stroke prevention and intervention, and ultimately minimize the physical, mental, and financial burden of arterial ischemic stroke. Here, we discuss recent advances in research for selected childhood stroke risk factors, highlighting the progress made in our understanding of etiologic mechanisms and pathophysiology, and address the future directions for acute and long-term treatment strategies for pediatric stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11910-013-0422-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954544PMC
January 2014

Acute seizures predict epilepsy after childhood stroke.

Ann Neurol 2013 Aug;74(2):249-56

Departments of Neurology, University of California, San Francisco, San Francisco, CA.

Objective: To determine incidence rates and predictors of epilepsy after childhood stroke and compare these to published estimates of 3 to 5% cumulative epilepsy incidence by 5 years poststroke in adults.

Methods: In a retrospective population-based study of children with stroke (29 days-19 years) in an integrated health care system (1993-2007), poststroke seizures were identified through electronic searches and confirmed by chart review. Stroke and seizure characteristics were abstracted from medical records. Survival analysis was used to determine rates and predictors of remote seizures and active epilepsy (anticonvulsant treatment for remote seizure within prior 6 months) at last follow-up.

Results: From a population of 2.5 million children, we identified 305 stroke cases. Over a median follow-up of 4.1 years (interquartile range = 1.8-6.8), 49 children had a first unprovoked remote seizure. The average annual incidence rate of first remote seizure was 4.4% (95% confidence interval [CI] = 3.3-5.8) with a cumulative risk of 16% (95% CI = 12-21) at 5 years and 33% (95% CI = 23-46) at 10 years poststroke. The cumulative risk of active epilepsy was 13% (95% CI = 9-18) at 5 years and 30% (95% CI = 20-44) at 10 years. Acute seizures at the time of stroke predicted development of active epilepsy (hazard ratio = 4.2, 95% CI = 2.2-8.1). At last follow-up, ⅓ of the children with active epilepsy had a recent breakthrough seizure despite anticonvulsant usage.

Interpretation: Unlike adults, children are uniquely vulnerable to epilepsy after stroke. Children with acute seizures at the time of stroke are at particularly high risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.23916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830669PMC
August 2013

High critical care usage due to pediatric stroke: results of a population-based study.

Neurology 2012 Jul 27;79(5):420-7. Epub 2012 Jun 27.

Department of Neurology, University of California, San Francisco, CA, USA.

Objectives: To measure intensive care unit (ICU) admission, intubation, decompressive craniotomy, and outcomes at discharge in a large population-based study of children with ischemic and hemorrhagic stroke.

Methods: In a retrospective study of all children enrolled in a Northern Californian integrated health care plan (1993-2003), we identified cases of symptomatic childhood stroke (age >28 days through 19 years) from inpatient and outpatient electronic diagnoses and radiology reports, and confirmed them through chart review. Data regarding stroke evaluation, management, and outcomes at discharge were abstracted. Intensive care unit (ICU) admission, intubation, and decompressive neurosurgery rates were measured, and multivariate logistic regression was used to identify predictors of critical care usage and outcomes at discharge.

Results: Of 256 cases (132 hemorrhagic and 124 ischemic), 61% were admitted to the ICU, 32% were intubated, and 11% were treated with a decompressive neurosurgery. Rates were particularly high among children with hemorrhagic stroke (73% admitted to the ICU, 42% intubated, and 19% received a decompressive neurosurgery). Altered mental status at presentation was the most robust predictor for all 3 measures of critical care utilization. Neurologic deficits at discharge were documented in 57%, and were less common after hemorrhagic than ischemic stroke: 48% vs 66% (odds ratio 0.5, 95% confidence interval 0.3-0.8). Case fatality was 4% overall, 7% among children admitted to the ICU, and was similar between ischemic and hemorrhagic stroke.

Conclusions: ICU admission is frequent after childhood stroke and appears to be justified by high rates of intubation and surgical decompression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0b013e3182616fd7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405247PMC
July 2012

Recent advances in childhood arterial ischemic stroke.

Curr Atheroscler Rep 2010 Jul;12(4):217-24

University of California, San Francisco, 94143-0114, USA.

Although many underlying diseases have been reported in the setting of childhood arterial ischemic stroke, emerging research demonstrates that non-atherosclerotic intracerebral arteriopathies in otherwise healthy children are prevalent. Minor infections may play a role in arteriopathies that have no other apparent underlying cause. Although stroke in childhood differs in many aspects from adult stroke, few systematic studies specific to pediatrics are available to inform stroke management. Treatment trials of pediatric stroke are required to determine the best strategies for acute treatment and secondary stroke prevention. The high cost of pediatric stroke to children, families, and society demands further study of its risk factors, management, and outcomes. This review focuses on the recent findings in childhood arterial ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11883-010-0113-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878594PMC
July 2010

Infant botulism, type F, presenting at 54 hours of life.

Pediatr Neurol 2005 Mar;32(3):193-6

University of California-San Francisco (UCSF) School of Medicine, 521 Parnassus Avenue, San Francisco, CA 94143-0663, USA.

We report a case of botulism in a 54-hour-old infant with rapidly progressive fulminant paralysis and rapid spontaneous recovery atypical for infant botulism. Clostridium baratii and type F botulinum neurotoxin were isolated from the patient's stool. This unique presentation with rapid recovery is consistent with pharmacokinetics of type F botulinum neurotoxin. Interestingly, a muscle biopsy also revealed pathologic changes early in the disease course. This article reports the youngest known case of infant botulism and only the third reported case of this disease caused by type F neurotoxin. Botulism should be considered in patients of any age with subacute or acute neuromuscular weakness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2004.09.003DOI Listing
March 2005
-->