ABSTRACT
BACKGROUND: E-learning has become commonplace in medical education. Incorporation of multimedia, clinical cases, and interactive elements has increased its attractiveness over textbooks. Although there has been an expansion of e-learning in medicine, the feasibility of e-learning in pediatric neurology is unclear. This study evaluates knowledge acquisition and satisfaction using pediatric neurology e-learning compared to conventional learning. METHODS: Residents of Canadian pediatrics, neurology, and pediatric neurology programs and medical students from Queens University, Western University, and the University of Ottawa were invited to participate. Learners were randomly assigned two review papers and two ebrain modules in a four-topic crossover design. Participants completed pre-tests, experience surveys, and post-tests. We calculated the median change in score from pre-test to post-test and constructed a mixed-effects model to determine the effect of variables on post-test scores. RESULTS: In total, 119 individuals participated (53 medical students; 66 residents). Ebrain had a larger positive change than review papers in post-test score from pre-test score for the pediatric stroke learning topic but a smaller positive change for Duchenne muscular dystrophy, childhood absence epilepsy, and acute disseminated encephalomyelitis. Learning topics showed statistical relationship to post-test scores (p = 0.04). Depending on topic, 57-92% (N = 59-66) of respondents favored e-learning over review article learning. CONCLUSIONS: Ebrain users scored higher on post-tests than review paper users. However, the effect is small and it is unclear if it is educationally meaningful. Although the difference in scores may not be substantially different, most learners preferred e-learning. Future projects should focus on improving the quality and efficacy of e-learning modules.
Subject(s)
Computer-Assisted Instruction , Education, Medical , Neurology , Pediatrics , Humans , Canada , Neurology/education , Students, Medical , Cross-Over Studies , Pediatrics/educationABSTRACT
BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.
Subject(s)
Cerebral Revascularization , Moyamoya Disease , Stroke , Child , Humans , Delphi Technique , Moyamoya Disease/surgery , Stroke/etiology , Perioperative Care , Postoperative Care , Cerebral Revascularization/adverse effects , Treatment Outcome , Retrospective StudiesABSTRACT
Neurological morbidity is common after pediatric stroke, with moderate to severe deficits that can significantly impact education and social function. Care and recovery occur in phases distinguished by the time interval after stroke onset. These phases include the hyperacute and acute periods in which the focus is on cerebral reperfusion and prevention of neurological deterioration, followed by the subacute and chronic phases in which the focus is on secondary stroke prevention and mitigation of disability through rehabilitation, adaptation, and reintegration into the community. In this article, a multidisciplinary group of pediatric stroke experts review the stages of recovery after pediatric stroke with an emphasis on critical assessment time points. Our goal is to encourage increased standardization of outcome assessment to facilitate future clinical trials comparing various treatment and intervention options and advance optimized care for children with stroke.
Subject(s)
Stroke Rehabilitation , Stroke , Humans , Child , Stroke/diagnosis , Stroke/therapy , Outcome Assessment, Health CareABSTRACT
Neonatal hypoxic-ischemic encephalopathy is a clinical phenomenon that often results from perinatal asphyxia. To mitigate secondary neurologic injury, prompt initial assessment and diagnosis is needed to identify patients eligible for therapeutic hypothermia. However, occasionally neonates present with a clinical picture of hypoxic-ischemic encephalopathy without significant risk factors for perinatal asphyxia. We hypothesized that in patients with genetic abnormalities, the clinical manifestation of those abnormalities may overlap with hypoxic-ischemic encephalopathy criteria, potentially contributing to a causal misattribution. We reviewed 210 charts of infants meeting local protocol criteria for moderate to severe hypoxic-ischemic encephalopathy in neonatal intensive care units in Calgary, Alberta. All patients that met criteria for therapeutic hypothermia were eligible for the study. Data were collected surrounding pregnancy and birth histories, as well as any available genetic or metabolic testing including microarray, gene panels, whole-exome sequencing, and newborn metabolic screens. Twenty-eight patients had genetic testing such as microarray, whole-exome sequencing, or a gene panel, because of clinical suspicion. Ten of 28 patients had genetic mutations, including CDKL5, pyruvate dehydrogenase, CFTR, CYP21A2, ISY1, KIF1A, KCNQ2, SCN9A, MTFMT, and NPHP1. All patients lacked significant risk factors to support a moderate to severe hypoxic-ischemic encephalopathy diagnosis. Treatment was changed in 2 patients because of confirmed genetic etiology. This study demonstrates the importance of identifying genetic comorbidities as potential contributors to a hypoxic-ischemic encephalopathy phenotype in neonates. Early identification of clinical factors that support an alternate diagnosis should be considered when the patient's clinical picture is not typical of hypoxic-ischemic encephalopathy and could aid in both treatment decisions and outcome prognostication.
Subject(s)
Asphyxia Neonatorum , Hypothermia, Induced , Hypoxia-Ischemia, Brain , Pregnancy , Female , Infant, Newborn , Humans , Hypoxia-Ischemia, Brain/complications , Hypoxia-Ischemia, Brain/diagnostic imaging , Hypoxia-Ischemia, Brain/genetics , Retrospective Studies , Genetic Predisposition to Disease/genetics , Asphyxia/complications , Asphyxia/therapy , Asphyxia Neonatorum/complications , Hypothermia, Induced/methods , Kinesins , NAV1.7 Voltage-Gated Sodium Channel , Steroid 21-HydroxylaseABSTRACT
Documentation of performance provides feedback to medical trainees on their progress and is required by Programs as a record for monitoring whether trainees are achieving expectations against accepted standards. Despite the importance of performance documentation and the focus on improving feedback delivery in medical education, there has been little written in the literature on documentation best practices. Documentation is an essential skill that cannot be learned solely by observation, as most is confidential. However, teaching documentation of learner performance is rarely discussed. This article describes the authors' experience in teaching the skill of effective documentation of trainee performance for the purpose of providing feedback, monitoring progress, and recording evaluations.
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BACKGROUND/OBJECTIVES: Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive insults can have lifelong consequences. Hematopoietic cell transplantation (HCT) is an established curative therapy, and recent studies have demonstrated efficacy with reduced toxicity nonmyeloablative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality-of-life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT. DESIGN/METHODS: Retrospective cohort analysis of nine recipients with hemoglobin SS SCD who underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol. RESULTS: Mean full-scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ = 92.1, SD 9.0; n = 8) and 2 years post-HCT (mean FSIQ = 96.6; SD 11.1; N = 9). Neuropsychological functioning was largely average across all cognitive domains, and no pre/post-HCT differences were found to be statistically significant given the small sample size. However, effect sizes revealed moderate improvements in processing speed (Cohen's d = .72) and verbal memory (Cohen's d = .60) post-HCT, and declines in measures of attention (Cohen's d = -.54) and fine motor speed and dexterity (Cohen's d = -.94). Parents endorsed better quality of life (Cohen's d = .91), less impact of SCD on their family, and less worry about their child's future (Cohen's d = 1.44). CONCLUSION: Neuropsychological functioning in a sample of children and adolescents treated uniformly with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed.
Subject(s)
Anemia, Sickle Cell , Hematopoietic Stem Cell Transplantation , Adolescent , Anemia, Sickle Cell/therapy , Child , Hematopoietic Stem Cell Transplantation/methods , Humans , Quality of Life , Retrospective Studies , Siblings , Treatment OutcomeSubject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Brain Ischemia/complications , Cephalometry , Humans , Infant, Newborn , Intelligence , Stroke/complicationsABSTRACT
OBJECTIVE: To describe the development of the Pediatric Epilepsy Outcome-Informatics Project (PEOIP) at Alberta Children's Hospital (ACH), which was created to provide standardized, point-of-care data entry; near-time data analysis; and availability of outcome dashboards as a baseline on which to pursue quality improvement. METHODS: Stakeholders involved in the PEOIP met weekly to determine the most important outcomes for patients diagnosed with epilepsy, create a standardized electronic note with defined fields (patient demographics, seizure and syndrome type and frequency and specific outcomes- seizure type and frequency, adverse effects, emergency department visits, hospitalization, and care pathways for clinical decision support. These were embedded in the electronic health record from which the fields were extracted into a data display platform that provided patient- and population-level dashboards updated every 36 hours. Provider satisfaction and family experience surveys were performed to assess the impact of the standardized electronic note. RESULTS: In the last 5 years, 3,245 unique patients involving 13, 831 encounters had prospective, longitudinal, standardized epilepsy data accrued via point-of-care data entry into an electronic note as part of routine clinical care. A provider satisfaction survey of the small number of users involved indicated that the vast majority believed that the note makes documentation more efficient. A family experience survey indicated that being provided with the note was considered "valuable" or "really valuable" by 86% of respondents and facilitated communication with family members, school, and advocacy organizations. SIGNIFICANCE: The PEOIP serves as a proof of principle that information obtained as part of routine clinical care can be collected in a prospective, standardized, efficient manner and be used to construct filterable process/outcome dashboards, updated in near time (36 hours). This information will provide the necessary baseline data on which multiple of QI projects to improve meaningful outcomes for children with epilepsy will be based.
Subject(s)
Electronic Health Records , Epilepsy , Child , Documentation , Epilepsy/therapy , Humans , Prospective Studies , Quality ImprovementABSTRACT
BACKGROUND: Perinatal stroke is a leading cause of hemiparetic cerebral palsy and lifelong disability. Neurodevelopmental outcomes are difficult to predict and markers of long-term poor outcome continue to be investigated. Deceleration in growth of head circumference has been associated with worse developmental outcomes in neonatal brain injury. We hypothesized that perinatal stroke would result in decreased rates of head growth during childhood that would be associated with worse developmental outcomes. METHODS: Patients with magnetic resonance imaging (MRI)-confirmed neonatal arterial ischemic stroke and arterial presumed perinatal ischemic stroke were identified from a population-based research cohort (Alberta Perinatal Stroke Project). Demographics and occipital-frontal circumference data were collected from medical records. Head growth was compared to typically developing control charts using a 2-tailed t test. The Fisher exact test was used to examine associations between Pediatric Stroke Outcome Measures (PSOM) scores and occipital-frontal head circumference. RESULTS: Three hundred fifteen occipital-frontal head circumference measurements were collected from 102 patients (48 female, 54 male), over a median of 3.2 years (standard deviation = 5.18, range = 0-18.3). After 3 months for female patients and 1 year for male patients, occipital-frontal head circumference deviated and remained below normal growth trajectories (P < .05) with a large effect size (Cohen d >0.8). Poor outcome (PSOM ≥ 1) was associated with smaller occipital-frontal head circumference (P < .05). CONCLUSION: Head growth deceleration is observed in children with perinatal arterial ischemic stroke and is associated with poor outcome. Head circumference may be a tool to alert clinicians to the potential of abnormal neurologic outcome.
Subject(s)
Cephalometry/statistics & numerical data , Head/anatomy & histology , Head/growth & development , Adolescent , Cephalometry/methods , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging/methods , Male , Patient Acuity , Retrospective Studies , StrokeABSTRACT
BACKGROUND: Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management. METHODS: We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains. RESULTS: Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75-0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2). CONCLUSIONS: Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Adult , Brain Ischemia/diagnostic imaging , Brain Ischemia/therapy , Canada , Child , Child, Preschool , Fibrinolytic Agents/therapeutic use , Humans , Stroke/diagnostic imaging , Stroke/drug therapy , Tertiary Care Centers , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: Continuous spike and wave in slow-wave sleep (CSWS), an epileptic encephalopathy, occurs after perinatal stroke where it is associated with cognitive decline. CSWS features a distinct EEG pattern, electrical status epilepticus in sleep (ESES). Biomarkers for the prediction of ESES have not been identified but will facilitate earlier diagnosis and treatment. We hypothesized that spike-frequency and differences in power spectra would be predictive of subsequent ESES. METHODS: A cross-sectional study comparing EEG spike-frequency and Power before the development of ESES in patients with perinatal stroke, patients with focal epilepsy, and appropriate controls. RESULTS: 43 patients met the inclusion criteria; 11 stroke-ESES, 10 stroke controls, 14 epilepsy-ESES, 8 epilepsy controls. ESES patients had higher pre-diagnosis mean spike-frequency (24.0 ± 24 versus 6.6 ± 9.1 SW/min, p = 0.002) than patients that did not develop ESES; these differences present ~ 3 years before ESES diagnosis. Pre-diagnosis, normalized delta power (1-4 Hz) was higher in the stroke-ESES group (105.7 ± 58 dB/Hz) compared to stroke controls (57.4 ± 45 dB/Hz, p = 0.036). CONCLUSION: Spike-frequency and delta power may represent EEG biomarkers of the risk of developing ESES in children with perinatal stroke. SIGNIFICANCE: EEG biomarkers may be used by clinicians to assess which patients are more at-risk for ESES. Using spike-frequency, clinicians may be able to identify patients at risk of developing ESES.
Subject(s)
Brain/physiopathology , Status Epilepticus/physiopathology , Stroke/physiopathology , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Electroencephalography , Female , Humans , Male , Sleep/physiology , Status Epilepticus/etiology , Stroke/complicationsABSTRACT
BACKGROUND: Perinatal stroke encompasses multiple disease-specific cerebrovascular syndromes that cause lifelong neurodevelopmental morbidity for millions worldwide. Acute presentations include neonatal arterial ischemic stroke (NAIS), neonatal cerebral sinovenous thrombosis, and neonatal hemorrhagic stroke (NHS). Delayed presentations include arterial presumed perinatal ischemic stroke, periventricular venous infarction, and presumed perinatal hemorrhagic stroke. Our objective was to define the birth prevalence of all subtypes of perinatal stroke by using a population-based cohort. METHODS: The Alberta Perinatal Stroke Project is a research cohort established in 2008 in southern Alberta, Canada, with prospective (2008-2017) and retrospective (1990-2008) enrollment leveraging universal health care at a single tertiary care pediatric center. The primary outcome was the estimated birth prevalence of each perinatal stroke syndrome, secondary outcomes were birth prevalence over time, sex ratios, and change in age at diagnosis. Analysis included Poisson regression, Wilcoxon rank test, and Fisher exact test. RESULTS: The overall estimated birth prevalence of term-born perinatal stroke was 1:1100. The estimated birth prevalence was 1:3000 for NAIS, 1:7900 for arterial presumed perinatal ischemic stroke, 1:6000 for periventricular venous infarction, 1:9100 for cerebral sinovenous thrombosis, 1:6800 for NHS, and 1:65000 for presumed perinatal hemorrhagic stroke. The apparent birth prevalence of NAIS and NHS increased over time. There were more males affected than females. The age at diagnosis decreased for late-presenting stroke types. CONCLUSIONS: The estimated birth prevalence of term perinatal stroke is higher than previous estimates, which may be explained by population-based sampling of disease-specific states. This emphasizes the need for further studies to better understand the disease-specific pathophysiology to improve treatment and prevention strategies.
Subject(s)
Stroke/epidemiology , Age Factors , Alberta/epidemiology , Brain Ischemia/diagnostic imaging , Brain Ischemia/epidemiology , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/epidemiology , Cerebral Infarction/diagnostic imaging , Cerebral Infarction/epidemiology , Cohort Studies , Female , Hospitals, Pediatric , Humans , Infant, Newborn , Intracranial Thrombosis/diagnostic imaging , Intracranial Thrombosis/epidemiology , Male , Poisson Distribution , Prevalence , Prospective Studies , Retrospective Studies , Sex Distribution , Statistics, Nonparametric , Stroke/complications , Stroke/diagnostic imaging , Tertiary Care CentersABSTRACT
BACKGROUND: Acute flaccid myelitis (AFM) is characterised by rapid onset of limb weakness with spinal cord grey-matter abnormalities on MRI scan. We aimed to assess whether detection of enterovirus in respiratory or other specimens can help predict prognosis in children with AFM. METHODS: In this nationwide, longitudinal study, we evaluated the significance of detection of enterovirus in any sample in predicting outcomes in a cohort of Canadian children younger than 18 years presenting with AFM to tertiary paediatric hospitals in Canada in 2014 and 2018. All patients fulfilled the 2015 US Centers for Disease Control and Prevention case definition for definite AFM or probable AFM. Clinical data, laboratory findings, treatment, and neuroimaging results were collected (follow up period up to 5 years). We assessed neurological function and motor outcomes using Kurtzke's Expanded Disability Status Scale (EDSS) and a Weakest Limb Score. FINDINGS: 58 children with AFM (median age 5·1 years, IQR 3·8-8·3) were identified across five of Canada's ten provinces and three territories. 25 (43%) children had enterovirus detected in at least one specimen: 16 (64%) with EV-D68, two (8%) with EV-A71, two (8%) with coxsackievirus, 10 (40%) with untyped enterovirus. Children who were enterovirus positive were more likely than those that were negative to have had quadriparesis (12 [48%] of 25 vs four [13%] of 30; p=0·028), bulbar weakness (11 [44%] of 25 vs two [7%] of 30; p=0·028), bowel or bladder dysfunction (14 [56%] of 25 vs seven [23%] of 30; p=0·040), cardiovascular instability (nine [36%] of 25 vs one [3%] of 30; p=0·028), and were more likely to require intensive care unit admission (13 [52%] of 25 vs 5 [17%] of 30; p=0·028). On MRI, most children who were enterovirus positive showed brainstem pontine lesions (14 [61%] of 23), while other MRI parameters did not correlate with enterovirus status. Median EDSS of enterovirus positive (EV+) and enterovirus negative (EV-) groups was significantly different at all timepoints: baseline (EDSS 8·5, IQR 4·1-9·5 vs EDSS 4·0, IQR 3·0-6·0; p=0·0067), 3 months (EDSS 4·0, IQR 3·0-7·4 vs EDSS 3·0, IQR 1·5-4·3; p=0·0067), 6 months (EDSS 3·5, IQR 3·0-7·0 vs EDSS 3·0, IQR 1·0-4·0; p=0·029), and 12 months (EDSS 3·0, IQR 3·0-6·9 vs EDSS 2·5 IQR 0·3-3·0; p=0·0067). Kaplan-Meier survival analysis of a subgroup of patients showed significantly poorer motor recovery among children who tested positive for enterovirus than for those who tested negative (p=0·037). INTERPRETATION: Detection of enterovirus in specimens from non-sterile sites at presentation correlated with more severe acute motor weakness, worse overall outcomes and poorer trajectory for motor recovery. These results have implications for rehabilitation planning as well as counselling of families of children with these disorders. The findings of this study support the need for early testing for enterovirus in non-CNS sites in all cases of AFM. FUNDING: None.
Subject(s)
Central Nervous System Viral Diseases , Enterovirus/isolation & purification , Muscle Weakness , Myelitis , Neuromuscular Diseases , Spinal Cord/diagnostic imaging , Canada/epidemiology , Central Nervous System Viral Diseases/diagnosis , Central Nervous System Viral Diseases/epidemiology , Central Nervous System Viral Diseases/microbiology , Central Nervous System Viral Diseases/therapy , Child, Preschool , Enterovirus/classification , Female , Hospitals, Pediatric/statistics & numerical data , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/statistics & numerical data , Male , Motor Skills , Muscle Weakness/diagnosis , Muscle Weakness/etiology , Muscle Weakness/rehabilitation , Myelitis/diagnosis , Myelitis/epidemiology , Myelitis/microbiology , Myelitis/therapy , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/epidemiology , Neuromuscular Diseases/microbiology , Neuromuscular Diseases/therapy , Outcome Assessment, Health Care , Prognosis , Recovery of FunctionABSTRACT
OBJECTIVE: To examine the relationship between neonatal inflammatory cytokines and perinatal stroke using a systems biology approach analyzing serum and blood-spot cytokines from 47 patients. METHODS: This was a population-based, controlled cohort study with prospective and retrospective case ascertainment. Participants were recruited through the Alberta Perinatal Stroke Project. Stroke was classified as neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or periventricular venous infarction (PVI). Biosamples were stored blood spots (retrospective) and acute serum (prospective). Controls had comparable gestational and maternal ages. Sixty-five cytokines were measured (Luminex). Hierarchical clustering analysis was performed to create heat maps. The Fisher linear discriminant analysis was used to create projection models to determine discriminatory boundaries between stroke types and controls. RESULTS: A total of 197 participants were analyzed (27 with NAIS, 8 with APPIS, 12 with PVI, 150 controls). Cytokines were quantifiable with quality control measures satisfied (standards testing, decay analysis). Linear discriminant analysis had high accuracy in using cytokine profiles to separate groups. Profiles in participants with PVI and controls were similar. NAIS separation was accurate (sensitivity 77%, specificity 97%). APPIS mapping was also distinguishable from NAIS (sensitivity 86%, specificity 99%). Classification tree analysis generated similar diagnostic accuracy. CONCLUSIONS: Unique inflammatory biomarker signatures are associated with specific perinatal stroke diseases. Findings support an acquired pathophysiology and suggest the possibility that at-risk pregnancies might be identified to develop prevention strategies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that differences in acute neonatal serum cytokine profiles can discriminate between patients with specific perinatal stroke diseases and controls.
Subject(s)
Brain Ischemia/immunology , Cytokines/immunology , Inflammation/immunology , Stroke/immunology , Adult , Age of Onset , Brain Infarction/classification , Brain Infarction/diagnostic imaging , Brain Infarction/immunology , Brain Infarction/physiopathology , Brain Ischemia/classification , Brain Ischemia/diagnostic imaging , Brain Ischemia/physiopathology , Cluster Analysis , Discriminant Analysis , Dried Blood Spot Testing , Female , Humans , Infant, Newborn , Infarction, Middle Cerebral Artery/classification , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/immunology , Infarction, Middle Cerebral Artery/physiopathology , Intracranial Arterial Diseases/classification , Intracranial Arterial Diseases/diagnostic imaging , Intracranial Arterial Diseases/immunology , Intracranial Arterial Diseases/physiopathology , Linear Models , Magnetic Resonance Imaging , Male , Maternal Age , Paresis/physiopathology , Pre-Eclampsia/epidemiology , Pregnancy , Seizures/physiopathology , Smoking/epidemiology , Stroke/classification , Stroke/diagnostic imaging , Stroke/physiopathology , White Matter/diagnostic imaging , Young AdultABSTRACT
BACKGROUND: Pediatric cerebral sinovenous thrombosis is a treatable cause of brain injury, acute symptomatic seizures, and remote epilepsy. Our objective was to prospectively study epilepsy and outcomes in neonates and children one year after cerebral sinovenous thrombosis diagnosis. METHODS: Patients with cerebral sinovenous thrombosis were enrolled prospectively from 21 international sites through the Seizures in Pediatric Stroke Study. Clinical data, including acute symptomatic seizures and cerebral sinovenous thrombosis risk factors, were collected at diagnosis. A neuroradiologist who was unaware of the diagnosis reviewed acute imaging. At one year, outcomes including seizure recurrence, epilepsy diagnosis, antiepileptic drug use, and modified Engel score were collected. Outcomes were assessed using the modified Rankin score and the King's Outcome Scale for Childhood Head Injury. RESULTS: Twenty-four participants with cerebral sinovenous thrombosis were enrolled (67% male, 21% neonates). Headache was the most common presenting symptom in non-neonates (47%, nine of 19). Nine (37.5%) presented with acute symptomatic seizures. Six (25%; 95% confidence interval, 10% to 47%) developed epilepsy by one-year follow-up. No clinical predictors associated with epilepsy were identified. King's Outcome Scale for Childhood Head Injury and modified Rankin scores at one year were favorable in 71%. Half of the patients who developed epilepsy (three of six) did not have infarcts, hemorrhage, or seizures identified during the acute hospitalization. CONCLUSION: Our study provides a prospective estimate that epilepsy occurs in approximately one-quarter of patients by one year after diagnosis of cerebral sinovenous thrombosis. Later epilepsy can develop in the absence of acute seizures or parenchymal injury associated with the acute presentation.
Subject(s)
Epilepsy , Ischemic Stroke , Outcome Assessment, Health Care , Seizures , Sinus Thrombosis, Intracranial , Adolescent , Anticonvulsants/administration & dosage , Child , Child, Preschool , Epilepsy/diagnosis , Epilepsy/drug therapy , Epilepsy/etiology , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Ischemic Stroke/complications , Ischemic Stroke/diagnosis , Ischemic Stroke/therapy , Male , Seizures/diagnosis , Seizures/drug therapy , Seizures/etiology , Sinus Thrombosis, Intracranial/complications , Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/therapyABSTRACT
AIM: We aimed to characterize the phenotype and outcome of children with bilateral, large vessel perinatal arterial ischemic stroke. METHODS: Patients with bilateral, large vessel perinatal arterial ischemic stroke were identified from a large, population-based cohort (Alberta Perinatal Stroke Project). Subjects were included if stroke involving a major cerebral artery territory was documented in both cerebral hemispheres on magnetic resonance imaging. Standardized variables were extracted from charts including clinical presentations, associated potential risk factors, and outcomes. Outcome measures included the Pediatric Stroke Outcome Measure, Gross Motor Function Classification System, and epilepsy frequency score. Electroencephalographies were reviewed for sleep, epileptiform activity, and background. RESULTS: Of 174 children with perinatal arterial ischemic stroke, eight (5%) had bilateral large artery infarcts. Patients were followed for a mean of 9.7 years (range 1.8 to 14.6 years). One child died. All children had a total Pediatric Stroke Outcome Measure of ≥2 (median 8, range 2 to 10) and Gross Motor Function Classification System ≥ II. Seven of eight (88%) children had a history of epilepsy. CONCLUSIONS: Children with bilateral, large vessel perinatal stroke are at high risk of severe cognitive and motor sequelae. Epilepsy may also be more common than unilateral strokes. Cautious discussions with families regarding prognosis are recommended.
Subject(s)
Brain Ischemia/complications , Brain Ischemia/psychology , Developmental Disabilities/epidemiology , Stroke/complications , Stroke/psychology , Brain Ischemia/diagnostic imaging , Child , Child Development , Child, Preschool , Cognition , Cohort Studies , Developmental Disabilities/diagnostic imaging , Female , Humans , Infant, Newborn , Male , Motor Skills , Stroke/diagnostic imagingABSTRACT
Background: Stroke is a leading cause of perinatal brain injury with variable outcomes including cerebral palsy and epilepsy. The biological processes that underlie these heterogeneous outcomes are poorly understood. Alterations in developmental myelination are recognized as a major determinant of outcome in preterm brain injury but have not been explored in perinatal stroke. We aimed to characterize myelination in hemiparetic children after arterial perinatal stroke, hypothesizing that ipsilesional myelination would be impaired, the degree of which would correlate with poor outcome. Methods: Retrospective, controlled cohort study. Participants were identified through the Alberta Perinatal Stroke Project (APSP), a population-based research cohort (nâ¯>â¯400). Inclusion criteria were: 1) MRI-confirmed, unilateral arterial perinatal stroke, 2) T1-weighted MRI after 6â¯months of age, 3) absence of other neurological disorders, 4) neurological outcome that included at least one of the following tests - Pediatric Stroke Outcome Measure (PSOM), Assisting Hand Assessment (AHA), Melbourne Assessment (MA), neuropsychological evaluation (NPE), and robotic sensorimotor measurements. FreeSurfer software measured hemispheric asymmetry in myelination intensity (primary outcome). A second method using ImageJ software validated the detection of myelination asymmetry. A repeated measures ANOVA was used to compare perilesional, ipsilesional remote, and contralesional homologous region myelination between stroke cases and typically developing controls. Myelination metrics were compared to clinical outcome measures (t-test, Pearson's correlation). Results: Twenty youth with arterial stroke (mean age: 13.4⯱â¯4.2yo) and 27 typically developing controls (mean age: 12.5⯱â¯3.7yo) were studied in FreeSurfer. Participants with stroke demonstrated lower myelination in the ipsilesional hemisphere (pâ¯<â¯0.0001). Myelination in perilesional regions had lower intensity compared to ipsilesional remote areas (pâ¯<â¯.00001) and contralesional homologous areas (pâ¯<â¯0.00001). Ipsilesional remote regions had decreased myelination compared to homologous regions on the contralesional hemisphere (pâ¯=â¯0.016). Contralesional myelination was decreased compared to controls (pâ¯<â¯0.00001). Myelination metrics were not strongly associated with clinical motor, robotic sensorimotor, or neuropsychological outcomes though some complex tests requiring speeded responses had moderate effect sizes. Conclusion: Myelination of apparently uninjured brain in both the ipsilesional and contralesional hemispheres is decreased after perinatal stroke. Differences appear to radiate outward from the lesion. Further study is needed to determine clinical significance.
Subject(s)
Motor Cortex/diagnostic imaging , Nerve Fibers, Myelinated/pathology , Nerve Net/diagnostic imaging , Stroke/diagnostic imaging , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Motor Cortex/physiopathology , Nerve Fibers, Myelinated/physiology , Nerve Net/physiopathology , Retrospective Studies , Stroke/physiopathologyABSTRACT
BACKGROUND: Patients with arterial perinatal stroke often suffer long-term motor sequelae, difficulties in language, social development, and behaviour as well as epilepsy. Despite homogeneous lesions, long-term behavioural and cognitive outcomes are variable and unpredictable. Sleep-related epileptic encephalopathies can occur after early brain injury and are associated with global developmental delays. We hypothesized that sleep-potentiated epileptiform abnormalities are associated with worse developmental outcomes after perinatal stroke. METHODS: Participants were identified from a population-based cohort (Alberta Perinatal Stroke Project). Inclusion criteria were magnetic resonance imaging-confirmed arterial perinatal stroke, age 4 to 18 years, electroencephalogram (EEG) including sleep, and comprehensive neuropsychological evaluation. Sleep-related EEG abnormalities were categorized by an epileptologist blinded to the cognitive outcome. Associations between EEG classification and neuropsychological outcomes were explored (t tests, Bonferroni correction for multiple comparisons). RESULTS: Of 128 potentially eligible participants, 34 (53% female) had complete EEG (mean age, 8.1 years; range, 0.2-16.4) and neuropsychology testing (mean age, 9.8 years; range 4.4-16.7). Twelve (35%) were classified as having electrical status epilepticus in sleep. Patients with abnormal EEGs were more likely to have statistically worse scores when corrected for multiple comparisons, in receptive language (median, 1st percentile; IQR 1-7th percentile; p<0.05), and externalizing behaviours (median, 82nd percentile; IQR, 79-97th percentile; p<0.05). CONCLUSIONS: Developmental outcome in language and behaviour in children with arterial perinatal stroke is associated with electrical status epilepticus in sleep. Increased screening with sleep EEG is suggested, whereas further studies are necessary to determine if treatment of EEG abnormalities can improve outcome.