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Find video protocols related to scientific articles indexed in Pubmed.
Diagnostic delays in paediatric stroke.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 10-25-2014
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Stroke is a major cause of mortality in children. Conditions that mimic stroke also cause severe morbidity and require prompt diagnosis and treatment. We have investigated the time to diagnosis in a cohort of children with stroke.
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Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia.
N. Engl. J. Med.
PUBLISHED: 08-21-2014
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Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.
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Factors predicting future ACS episodes in children with sickle cell anemia.
Am. J. Hematol.
PUBLISHED: 07-29-2014
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While a doctor-diagnosis of asthma is associated with an increased risk of pain and acute chest syndrome (ACS) in children with sickle cell anemia (SCA), little is known about the relationship between specific asthma characteristics and clinical factors and future morbidity in children with SCA. We evaluated the relationship between (i) asthma risk factors at the time of a clinical visit (respiratory symptoms, maternal history of asthma, allergy skin tests, spirometry results) and (ii) the known risk factor of ACS early in life, on prospective pain and ACS episodes in a cohort of 159 children with SCA followed from birth to a median of 14.7 years. An ACS episode prior to 4 years of age, (incidence rate ratio [IRR] = 2.84; P < 0.001], female gender (IRR = 1.80; P = 0.009), and wheezing causing shortness of breath (IRR = 1.68; P = 0.042) were associated with future ACS rates. We subsequently added spirometry results (obstruction defined as FEV1 /FVC less than the lower limits of normal; and bronchodilator response, FEV1 ? 12%) and prick skin test responses to the model. Only ? 2 positive skin tests had a significant effect (IRR 1.87; P = 0.01). Thus, early in life ACS events, wheezing causing shortness of breath, and ? 2 positive skin tests predict future ACS events. Am. J. Hematol. 89:E212-E217, 2014. © 2014 Wiley Periodicals, Inc.
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Obstructive sleep apnea and sickle cell anemia.
Pediatrics
PUBLISHED: 07-14-2014
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To ascertain the prevalence of and risk factors for obstructive sleep apnea syndrome (OSAS) in children with sickle cell anemia (SCA).
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Silent cerebral infarction, income, and grade retention among students with sickle cell anemia.
Am. J. Hematol.
PUBLISHED: 07-08-2014
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Children with sickle cell anemia have a higher-than-expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross-sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5-15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia.
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Primary stroke prevention in Nigerian children with sickle cell disease (SPIN): Challenges of conducting a feasibility trial.
Pediatr Blood Cancer
PUBLISHED: 05-30-2014
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The majority of children with sickle cell disease (SCD), approximately 75%, are born in sub-Saharan Africa. For children with elevated transcranial Doppler (TCD) velocity, regular blood transfusion therapy for primary stroke prevention is standard care in high income countries, but is not feasible in sub-Saharan Africa.
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Arterial spin labeling characterization of cerebral perfusion during normal maturation from late childhood into adulthood: normal 'reference range' values and their use in clinical studies.
J. Cereb. Blood Flow Metab.
PUBLISHED: 01-08-2014
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The human brain changes structurally and functionally during adolescence, with associated alterations in cerebral perfusion. We performed dynamic arterial spin labeling (ASL) magnetic resonance imaging in healthy subjects between 8 and 32 years of age, to investigate changes in cerebral hemodynamics during normal development. In addition, an inversion recovery sequence allowed quantification of changes in longitudinal relaxation time (T?) and equilibrium longitudinal magnetization (M?). We present mean and reference ranges for normal values of T?, M?, cerebral blood flow (CBF), bolus arrival time, and bolus duration in cortical gray matter, to provide a tool for identifying age-matched perfusion abnormalities in this age range in clinical studies. Cerebral blood flow and T? relaxation times were negatively correlated with age, without gender or hemisphere differences. The same was true for M? anteriorly, but posteriorly, males but not females showed a significant decline in M? with increasing age. Two examples of the clinical utility of these data in identifying age-matched perfusion abnormalities, in Sturge-Weber syndrome and sickle cell anemia, are illustrated.
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Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania.
Br. J. Haematol.
PUBLISHED: 01-05-2014
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Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co-inheritance in SCA of alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co-inheritance of these polymorphisms on CBFv in 601 stroke-free Tanzanian SCA patients aged <24 years. Homozygosity for alpha-thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild-type (?-coefficient -16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha-thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35-0·8] & RRR = 0·43 [95% CI:0·23-0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17-0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co-inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha-thalassaemia in reducing risk of abnormal CBFv.
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Headache and migraine in children with sickle cell disease are associated with lower hemoglobin and higher pain event rates but not silent cerebral infarction.
J. Pediatr.
PUBLISHED: 01-02-2014
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To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts.
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Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study.
Lancet Neurol
PUBLISHED: 12-02-2013
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Arterial ischaemic stroke is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood arterial ischaemic stroke have been undertaken. We aimed to investigate the epidemiology and clinical features of childhood arterial ischaemic stroke in a population-based cohort.
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Varicella zoster virus central nervous system immune reconstitution inflammatory syndrome presenting in a child.
Pediatr. Infect. Dis. J.
PUBLISHED: 10-22-2013
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A HIV-positive child presented with acute onset of right hemiplegia, facial palsy and dysphasia 4 weeks after commencing highly active antiretroviral therapy. Magnetic resonance imaging confirmed a left-sided cerebral infarct. Cerebrospinal fluid polymerase chain reaction was positive for varicella zoster virus. This is the first reported pediatric case of varicella zoster virus-related immune reconstitution inflammatory syndrome involving the central nervous system.
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Unexpected relationship between tympanometry and mortality in children with nontraumatic coma.
Pediatrics
PUBLISHED: 08-12-2013
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We sought to further examine the relationship between tympanometry and mortality after noting an unexpected association on assessment of baseline data of a study whose primary aim was to investigate the utility of noninvasive tympanic membrane displacement measurement for monitoring intracranial pressure in childhood coma.
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Fosphenytoin for seizure prevention in childhood coma in Africa: a randomized clinical trial.
J Crit Care
PUBLISHED: 07-01-2013
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We conducted a double-blind trial to determine whether a single intramuscular injection of fosphenytoin prevents seizures and neurologic sequelae in children with acute coma.
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Environmental tobacco smoke and airway obstruction in children with sickle cell anemia.
Chest
PUBLISHED: 05-18-2013
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The contribution of environmental tobacco smoke (ETS) exposure to pulmonary morbidity in children with sickle cell anemia (SCA) is poorly understood. We tested the hypothesis that children with SCA and ETS exposure would have an increased prevalence of obstructive lung disease and respiratory symptoms compared with children with SCA and no ETS exposure.
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Subcortical and cerebellar volumetric deficits in paediatric sickle cell anaemia.
Br. J. Haematol.
PUBLISHED: 05-07-2013
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Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white and cortical grey matter, but there are few data on subcortical volumes. We analysed retrospective magnetic resonance imaging (MRI) data in 26 SCA patients and 20 controls, comparing mean subcortical volumes between three groups: controls, SCA with SCI (n = 13) and SCA without visible abnormality (n = 13). Specific volumetric differences were found in the hippocampus, amygdala, pallidum, caudate, putamen, thalamus, and cerebellum. This is the first study to demonstrate subcortical volume change in SCA, with the most severe volumetric deficits occurring in children with SCI seen on MRI.
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Coma and brain death.
Handb Clin Neurol
PUBLISHED: 04-30-2013
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Coma must persist for at least 1 hour to distinguish it from transient unconsciousness. Traumatic and nontraumatic coma are common problems in pediatric practice with high mortality and morbidity. Emergency neuroimaging is worthwhile even when etiology is known, as treatable complications, such as venous sinus thrombosis, as well as extradural and intracerebral hemorrhage, are commonly diagnosed. There is a wide range of possible etiologies in the previously well child, most of which may be diagnosed from neuroimaging and laboratory testing available as an emergency, or can be treated presumptively, e.g., with antimicrobials for infections. The modified Childs Glasgow Coma Scale (CGCS) for recording depth of consciousness in children is widely used and should be supplemented by examination for the signs of reversible central and uncal brainstem herniation due to acute intracranial hypertension. An evidence-based guideline for the investigation and management of decreased level of consciousness in children, written by an expert panel using the DELPHI principles, is available. Monitoring and rehabilitation should also be part of the management plan. Etiology, depth and duration of coma, and serial neurophysiology and imaging are predictors of outcome in survivors but must be interpreted cautiously. There are no reports of children meeting adult brain death criteria making good neurological recovery.
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Acute silent cerebral ischemic events in children with sickle cell anemia.
JAMA Neurol
PUBLISHED: 03-27-2013
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Irregular, sporadic episodes of ischemic brain injury are known to occur in sickle cell anemia (SCA), resulting in overt stroke and silent cerebral infarction. Ongoing ischemia in other organs is common in SCA but has never been documented in the brain.
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Delayed extradural haemorrhage: a case for intracranial pressure monitoring in sedated children with traumatic brain injury within tertiary centres.
BMJ Case Rep
PUBLISHED: 02-20-2013
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A 15-year-old girl sustained a mild isolated traumatic brain injury  following a pedestrian road traffic accident. She was ventilated for head computed tomography (CT) scan which revealed no intracranial abnormalities. Ventilation was not withdrawn until 15 h later when poor neurological recovery prompted urgent repeat CT, which demonstrated a delayed extradural haemorrhage (EDH). She underwent surgical evacuation, and intracranial pressure (ICP) monitoring was initiated postoperatively. She developed persistently raised ICP resistant to medical therapy, prompting further CT. This showed a recurrence of the delayed EDH requiring further surgical drainage. She made a good neurological recovery. There should be a low threshold for repeat CT to exclude delayed EDH when neurological status is poor despite normal CT soon after initial primary injury. ICP monitoring should be undertaken in children and adolescents who have normal initial CT, but in whom serial neurological assessment is not possible owing to sedation.
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Hematological and Genetic Predictors of Daytime Hemoglobin Saturation in Tanzanian Children with and without Sickle Cell Anemia.
ISRN Hematol
PUBLISHED: 01-01-2013
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Low hemoglobin oxygen saturation (SpO2) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO2 in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO2 was 97% (IQ range 94-99%) in SCA (N = 458), lower (P < 0.0001) than non-SCA (median 99%, IQ range 98-100%; N = 394). Within SCA, associations with SpO2 were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (P < 0.001, Adj r (2) = 0.09). In non-SCA only age correlated with SpO2. ?-thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient -0.60, P < 0.0001). In multivariable models, lower SpO2 correlated with higher MCH (?-coefficient -0.32, P < 0.001) or with decreased copies of ?-thalassemia 3.7 deletion (?-coefficient 1.1, P < 0.001), and independently in both models with lower HbF% (?-coefficient 0.15, P < 0.001) and Glucose-6-Phosphate Dehydrogenase genotype (?-coefficient -1.12, P = 0.012). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO2 in children with SCA. Potential mechanisms and implications are discussed.
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Nocturnal oxygen desaturation and disordered sleep as a potential factor in executive dysfunction in sickle cell anemia.
J Int Neuropsychol Soc
PUBLISHED: 11-24-2011
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Previous research has identified cognitive impairment in children with sickle cell anemia (SCA, Hemoglobin SS) compared with controls, partly accounted for by overt neuropathology after clinical stroke, "covert" ("silent") infarction, and severity of anemia. However, cognitive deficits have also been identified in children with SCA with no history of stroke and a normal T2-weighted magnetic resonance imaging (MRI) scan. Our aim was to investigate whether nocturnal hemoglobin oxygen desaturation and sleep fragmentation could be associated with cognitive impairment in children with SCA. We assessed 10 children with SCA (9 with normal MRI) using neuropsychological measures of executive function. Cognitive assessment was immediately followed by overnight polysomnography to record nocturnal hemoglobin oxygen saturation and sleep arousals. Decreases in hemoglobin oxygen saturation and/or increased sleep arousals were associated with reduced performance on cognitive assessment. Nocturnal hemoglobin oxygen desaturation and sleep fragmentation may be a contributing factor to executive dysfunction in SCA.
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Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure.
Blood
PUBLISHED: 11-17-2011
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The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbS?° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.
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Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus: validation of a success score that predicts long-term outcome.
J Neurosurg Pediatr
PUBLISHED: 11-03-2011
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The goal of this study was to externally validate the proposed Endoscopic Third Ventriculostomy Success Score (ETVSS), which predicts successful treatment for hydrocephalus on the basis of a childs individual characteristics.
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Seizure-induced miosis.
Epilepsia
PUBLISHED: 11-02-2011
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Ictal autonomic pupillary dilation is common; however, miosis is rare. We describe a case of focal seizures secondary to cortical dysplasia presenting with bilateral pupillary miosis, rendered seizure free by resective surgery. The seizure-onset zone was localized within the left middle parietal gyrus by intracranial electrographic recording. Seizure onset was coincident with focal left centroparietal fast spike activity on electroencephalography (EEG). A large region of the left frontocentral cortical dysplasia was demonstrated on magnetic resonance imaging (MRI). Complete resection of the area of cortical dysplasia and additional cortical regions of ictal activity, identified using intracranial EEG, rendered the patient seizure free.
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Nontraumatic coma in children and adolescents: diagnosis and management.
Neurol Clin
PUBLISHED: 10-29-2011
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The causes of nontraumatic coma (NTC) vary by country, season and period of data collection. Infective diseases are among the major worldwide causes of NTC. Nonaccidental head injury must be in the differential diagnosis. Genetic and ethnic susceptibilities to causes of coma are being recognized. A systematic history and examination are essential for diagnosis, early recognition of herniation syndromes, and management. The management of NTC is discussed, with reference to clinical approach, treatment of seizures, and increased intracranial pressure. Public health measures, education, early diagnosis, and prompt appropriate treatment are the foundations needed to reduce incidence and improve outcome.
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Cervical carotid artery disease in sickle cell anemia: clinical and radiological features.
Blood
PUBLISHED: 09-01-2011
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Cervical internal carotid artery (cICA) occlusion is a recognized cause of acute ischemic stroke (AIS) in sickle cell disease (SCD), but the associated clinical and radiologic features are not well described. We reviewed data on cervical magnetic resonance angiography (cMRA) performed prospectively in 67 patients (55 children) for indications including transcranial Doppler (TCD) abnormalities, AIS, or previous AIS. cICA lesions were seen in 10 (15%) patients, including 4 of 7 patients presenting with AIS, and appear to have been missed on first presentation in 4 of 10 patients with previous AIS. Radiologic features in 7 patients were consistent with dissection. In 2 patients, there was strong clinical and radiologic evidence for thromboembolic AIS, and this was also considered possible in 4 other patients. Three of the 4 AIS patients were anticoagulated acutely, and the nontreated patient had recurrent, probably thromboembolic, AIS. TCD findings were variable, but in 4 patients there were high velocities in the cerebral vessels contralateral to the cICA stenosis. We suggest that all patients with AIS should have cMRA during acute evaluation to identify cICA occlusions that may require anticoagulation. Routine screening of children with SCD should also include evaluation of neck vessels by carotid Doppler followed by cMRA if a cervical vascular lesion is suspected.
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Changing patterns of neuropsychological functioning in children living at high altitude above and below 4000 m: a report from the Bolivian Children Living at Altitude (BoCLA) study.
Dev Sci
PUBLISHED: 07-21-2011
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The brain is highly sensitive to environmental hypoxia. Little is known, however, about the neuropsychological effects of high altitude residence in the developing brain. We recently described only minor changes in processing speed in native Bolivian children and adolescents living at approximately 3700 m. However, evidence for loss of cerebral autoregulation above this altitude (4000 m) suggests a potential threshold of hypoxia severity over which neuropsychological functioning may be compromised. We conducted physiological and neuropsychological assessments in 62 Bolivian children and adolescents living at La Paz (?3700 m) and El Alto (?4100 m) in order to address this issue. Groups were equivalent in terms of age, gender, social class, schooling, parental education and genetic admixture. Apart from percentage of hemoglobin saturated with oxygen in arterial blood (%SpO(2)), participants did not differ in their basal cardiac and cerebrovascular performance as explored by heart rate, mean arterial pressure, end-tidal carbon dioxide, and cerebral blood flow velocity at the basilar, anterior, middle and posterior cerebral arteries. A comprehensive neuropsychological assessment was administered, including tests of executive functions, attention, memory and psychomotor performance. Participants living at extreme altitude showed lower levels of performance in all executive tests (Cohen effect size = -0.91), whereas all other domains remained unaffected by altitude of residence. These results are compatible with earlier physiological evidence of a transitional zone for cerebral autoregulation at an altitude of 4000 m. We now show that above this threshold, the developing brain is apparently increasingly vulnerable to neuropsychological deficit.
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Hypertension impairs vascular reactivity in the pediatric brain.
Stroke
PUBLISHED: 05-26-2011
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Chronic hypertension impairs cerebrovascular regulation in adults, but its effects on the pediatric population are unknown. The objective of this study was to investigate cerebrovascular abnormalities in hypertensive children and adolescents.
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Successful treatment of two paediatric cases of anti-NMDA receptor encephalitis with cyclophosphamide: the need for early aggressive immunotherapy in tumour negative paediatric patients.
Eur. J. Paediatr. Neurol.
PUBLISHED: 05-25-2011
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We describe the clinical course and treatment of three unrelated female patients ranging in age from 27 months to 14 years with anti-NMDA receptor encephalitis. The third case is reported as an addendum to the paper. None of the cases were paraneoplastic. All received initial immunotherapy consisting of steroids and IVIg, and two of them received 3 and 8 plasma exchanges respectively, without consistent or sustained clinical improvement. All three girls were then treated with monthly cycles of Cyclophosphamide. All had resolution of their movement disorder and a dramatic and sustained clinical improvement of their other symptoms in the domains of cognition, language and behaviour. The clinical improvement began after the first cycle in two and the second cycle in the third and continued with the subsequent cycles. None developed side-effects of treatment. In light of the recent review of the condition and our own clinical experience in the paediatric age group, we propose that second line immunotherapy should be considered early after failure of first line immunotherapy.
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Very good inter-rater reliability of Engel and ILAE epilepsy surgery outcome classifications in a series of 76 patients.
Seizure
PUBLISHED: 05-07-2011
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The inter-rater reliability, expressed as kappa score, k, of the Engel and International League Against Epilepsy (ILAE) classifications of epilepsy surgery seizure outcome has not previously been evaluated. In a consecutive series of 76 patients (40 male; 25 children), 75 undergoing resective and 1 disconnective surgery at a mean age of 27.5 years (13 months-62 years), one observer classified 88% (n=67) and a second observer classified 87% (n=66) of patients as either Engel I or II (free from or rare disabling seizures) after a median follow up of 36 months (range 12-92 months); comparably, both observers classified 84% (n=64) as ILAE 1-3. Correlation for Engel versus ILAE for observer 1 was 0.933 (p<.0005) and for observer 2 was 0.931 (p<.0005). Both ILAE (k 0.81, 95% confidence intervals 0.69, 0.91) and Engel (k 0.77, 95% CI 0.65, 0.87) classifications have very acceptable inter-rater reliability as well as significant correlation.
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Cardiac arrest and post resuscitation of the brain.
Eur. J. Paediatr. Neurol.
PUBLISHED: 03-28-2011
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Primary out-of-hospital cardiac arrest in childhood is rare but survival is a little better for children than for adults, although the prognosis for infants is very poor. Hypoxic-ischaemic encephalopathy after in-hospital cardiac arrest in children undergoing complicated treatment for previously untreatable conditions is now a common problem and is probably increasing. An additional ischaemic insult worsens the prognosis for other encephalopathies, such as that occurring after accidental or non-accidental head injury. For near-drowning, the prognosis is often good, provided that cardiopulmonary resuscitation (CPR) is commenced immediately, and the child gasps within 40 minutes of rescue and regains consciousness soon afterwards. The prognosis is much worse for the nearly drowned child admitted to casualty or the emergency room deeply unconscious with fixed dilated pupils, requiring continuing CPR and with an arterial pH <7, especially if there is little recovery by the time of admission to the intensive care unit. The use of adrenaline, sodium bicarbonate and calcium appears to worsen prognosis. Neurophysiology, specifically serial electroencephalography and evoked potentials, is the most useful tool prognostically, although neuroimaging and biomarkers may play a role. In a series of 89 patients studied after cardiac arrest in three London centres between 1982 and 1985, 39% recovered consciousness within one month. Twenty seven percent died a cardiac death whilst in coma, and the outcome in the remainder was either brain death or vegetative state. EEG and initial pH were the best predictors of outcome in this study. Seizures affected one third and were associated with deterioration and worse outcome. The advent of extracorporeal membrane oxygenation (ECMO) and the positive results of hypothermia trials in neonates and adults have rekindled interest in timely management of this important group of patients.
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Neurophysiological evidence for cognitive and brain functional adaptation in adolescents living at high altitude.
Clin Neurophysiol
PUBLISHED: 01-26-2011
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Neurophysiological methods were used to study the effects of high altitude living on brain functions in a subgroup of participants of the Bolivian Children Living at Altitude (BoCLA) project.
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Mortality in sickle cell anemia in Africa: a prospective cohort study in Tanzania.
PLoS ONE
PUBLISHED: 01-07-2011
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The World Health Organization has declared Sickle Cell Anemia (SCA) a public health priority. There are 300,000 births/year, over 75% in Africa, with estimates suggesting that 6 million Africans will be living with SCA if average survival reaches half the African norm. Countries such as United States of America and United Kingdom have reduced SCA mortality from 3 to 0.13 per 100 person years of observation (PYO), with interventions such as newborn screening, prevention of infections and comprehensive care, but implementation of interventions in African countries has been hindered by lack of locally appropriate information. The objective of this study was to determine the incidence and factors associated with death from SCA in Dar-es-Salaam.
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Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease.
Blood
PUBLISHED: 10-12-2010
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Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.
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Pituitary function at long-term follow-up of childhood traumatic brain injury.
J. Neurotrauma
PUBLISHED: 10-06-2010
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Pituitary dysfunction is a recognized sequela of traumatic brain injury (TBI), occurring in 10-83% of adult patients, but there are few data on the prevalence or natural history in childhood. Our objective was to determine pituitary function in children and young adults at least 4 years after TBI requiring pediatric intensive care unit (PICU) admission. The effects of TBI and hypopituitarism on height, adiposity, and quality of life (QOL) were also evaluated. Unselected patients discharged from the regional PICU with TBI (age?
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Investigation and management of childhood stroke.
Paediatr Child Health (Oxford)
PUBLISHED: 09-01-2010
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It is now clear that a number of paediatric emergencies with a neurological presentation, including hemiparesis, visual loss, seizures and coma, commonly have a vascular basis which may not be obvious on CT scan. Although many children do well, as there is significant mortality as well as morbidity for childhood stroke, in addition to a high risk for recurrence, making a diagnosis in the acute phase important. Venography and arteriography (including the neck vessels if the intracranial vessels are normal) are usually indicated despite the problems i.e. contrast CT requires a high dose of radiation while emergency MR usually requires anaesthesia and conventional arteriography carries a small risk of stroke. Surgical decompression may be life-saving in ischaemic as well as haemorrhagic stroke. It is unusual for children with anterior circulation stroke to be triaged quickly enough (<4.5 h) for thrombolysis but this may occasionally be appropriate in posterior circulation occlusion associated with coma, where the time window is longer (<12 h). Anticoagulation carries relatively low risk and may be of benefit for children with venous sinus thrombosis (acutely and when at risk subsequently) or extracranial dissection. Aspirin to attempt to reduce the recurrence risk is appropriate in the medium term for the majority of patients with arterial ischaemic stroke. Iron and B vitamin deficiencies should be excluded or treated.
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Outcome following decompressive craniectomy for malignant middle cerebral artery infarction in children.
Dev Med Child Neurol
PUBLISHED: 08-30-2010
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Mortality from malignant middle cerebral artery infarction (MMCAI) approaches 80% in adult series. Although decompressive craniectomy decreases mortality and leads to an acceptable outcome in selected adult patients, there are few data on MMCAI in children with stroke. This study evaluated the frequency of MMCAI and the use of decompressive craniectomy in children.
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Airway hyperresponsiveness in children with sickle cell anemia.
Chest
PUBLISHED: 08-19-2010
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The high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained.
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The effects of hypertension on the paediatric brain: a justifiable concern.
Lancet Neurol
PUBLISHED: 07-30-2010
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The prevalence of hypertension in children is increasing but its neurological effects are under-recognised. Here, we describe acute and chronic effects of childhood hypertension on the nervous system. Acute neurological involvement ranges from posterior reversible encephalopathy syndrome to, possibly, infarction and haemorrhage. Children with chronic hypertension are likely to have learning disabilities and deficiencies in executive function, which are potentially reversible with antihypertensive treatment. These cognitive defects may be secondary to abnormal regulation of cerebral blood flow. Raised blood pressure in childhood could also contribute to the early development of atherosclerosis, which can have both short-term and long-term adverse effects on vasculature. Clinical studies are needed to better define the full clinical range of paediatric hypertension on a childs nervous system. Furthermore, accurate biomarkers to define cognitive abnormalities and cerebral involvement need to be identified.
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Cerebral venous sinus (sinovenous) thrombosis in children.
Neurosurg. Clin. N. Am.
PUBLISHED: 06-22-2010
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Cerebral venous sinus (sinovenous) thrombosis (CSVT) in childhood is a rare, but underrecognized, disorder, typically of multifactorial etiology, with neurologic sequelae apparent in up to 40% of survivors and mortality approaching 10%. There is an expanding spectrum of perinatal brain injury associated with neonatal CSVT. Although there is considerable overlap in risk factors for CSVT in neonates and older infants and children, specific differences exist between the groups. Clinical symptoms are frequently nonspecific, which may obscure the diagnosis and delay treatment. While morbidity and mortality are significant, CSVT recurs less commonly than arterial ischemic stroke in children. Appropriate management may reduce the risk of recurrence and improve outcome, however there are no randomized controlled trials to support the use of anticoagulation in children. Although commonly employed in many centers, this practice remains controversial, highlighting the continued need for high-quality studies. This article reviews the literature pertaining to pediatric venous sinus thrombosis.
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Development of aptitude at altitude.
Dev Sci
PUBLISHED: 05-07-2010
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Millions of people currently live at altitudes in excess of 2500 metres, where oxygen supply is limited, but very little is known about the development of brain and behavioural function under such hypoxic conditions. We describe the physiological, cognitive and behavioural profile of a large cohort of infants (6-12 months), children (6-10 years) and adolescents (13-16 years) who were born and are living at three altitude locations in Bolivia ( approximately 500 m, approximately 2500 m and approximately 3700 m). Level of haemoglobin oxygen saturation and end-tidal carbon dioxide were significantly lower in all age groups living above 2500 metres, confirming the presence of hypoxia and hypocapnia, but without any detectable detriment to health. Infant measures of neurodevelopment and behaviour yielded comparable results across altitude groups. Neuropsychological assessment in children and adolescent groups indicated a minor reduction in psychomotor speed with increasing altitude, with no effect of age. This may result from slowing of underlying brain activity in parallel with reduced cerebral metabolism and blood flow, evidenced here by reduced cerebral blood flow velocity, particularly in the basilar artery, in children and adolescents. The proportion of European, Native American and African genetic admixture was comparable across altitude groups, suggesting that adaptation to high altitude in these children occurred in response to chronic hypoxic exposure irrespective of ethnic origin. Thus, psychomotor slowing is proposed to be an adaptive rather than a deficient trait, perhaps enabling accuracy of mental activity in hypoxic conditions.
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Iron deficiency and acute seizures: results from children living in rural Kenya and a meta-analysis.
PLoS ONE
PUBLISHED: 04-09-2010
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There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area.
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Left ventricular hypertrophy and diastolic dysfunction in children with sickle cell disease are related to asleep and waking oxygen desaturation.
Blood
PUBLISHED: 04-08-2010
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Premature death and cardiac abnormalities are described in individuals with sickle cell disease (SCD), but the mechanisms are not well characterized. We tested the hypothesis that cardiac abnormalities in children with SCD are related to sleep-disordered breathing. We enrolled 44 children with SCD (mean age, 10.1 years; range, 4-18 years) in an observational study. Standard and tissue Doppler echocardiography, waking oxygen saturation averaged over 5 minutes, and overnight polysomnography were obtained in participants, each within 7 days. Eccentric left ventricular (LV) hypertrophy was present in 46% of our cohort. After multivariable adjustment, LV mass index was inversely related to average asleep and waking oxygen saturation. For every 1% drop in the average asleep oxygen saturation, there was a 2.1 g/m(2.7) increase in LV mass index. LV diastolic dysfunction, as measured by the E/E ratio, was present in our subjects and was also associated with low oxygen saturation (sleep or waking). Elevated tricuspid regurgitant velocity (> or = 2.5 m/sec), a measure of pulmonary hypertension, was not predicted by either oxygen saturation or sleep variables with multivariable logistic regression analysis. These data provide evidence that low asleep and waking oxygen saturations are associated with LV abnormalities in children with SCD.
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Stroke and cerebrovascular disorders.
Curr. Opin. Pediatr.
PUBLISHED: 11-03-2009
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Stroke and cerebrovascular disorders in childhood are a cause for significant morbidity in childhood. There is growing emphasis on understanding the mechanisms of stroke so as to inform developments in investigation and management.
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Cerebrovascular pathophysiology in pediatric traumatic brain injury.
J Trauma
PUBLISHED: 08-12-2009
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Traumatic brain injury (TBI) is the leading cause of traumatic morbidity and mortality in children. Although there is increasing information concerning TBI in adults and experimental animal models, relatively little is known regarding cerebrovascular pathophysiology specific to children.
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Auto-adjusting positive airway pressure in children with sickle cell anemia: results of a phase I randomized controlled trial.
Haematologica
PUBLISHED: 07-03-2009
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Low nocturnal oxygen saturation (SpO(2)) is implicated in complications of Sickle Cell Anemia (SCA). Twenty-four children with SCA were randomized to receive overnight auto-adjusting continuous positive airway pressure (auto-CPAP) with supplemental oxygen, if required, to maintain SpO(2) >or=94% or as controls. We assessed adherence, safety, sleep parameters, cognition and pain. Twelve participants randomized to auto-CPAP (3 with oxygen) showed improvement in Apnea/Hypopnea Index (p<0.001), average desaturation events >3%/hour (p=0.02), mean nocturnal SpO(2) (p=0.02) and cognition. Primary efficacy endpoint (Processing Speed Index) showed no group differences (p=0.67), but a second measure of processing speed and attention (Cancellation) improved in those receiving treatment (p=0.01). No bone marrow suppression, rebound pain or serious adverse event resulting from auto-CPAP use was observed. Six weeks of auto-CPAP therapy is feasible and safe in children with SCA, significantly improving sleep-related breathing disorders and at least one aspect of cognition.
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Risk factors for high cerebral blood flow velocity and death in Kenyan children with Sickle Cell Anaemia: role of haemoglobin oxygen saturation and febrile illness.
Br. J. Haematol.
PUBLISHED: 03-27-2009
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High cerebral blood flow velocity (CBFv) and low haemoglobin oxygen saturation (SpO(2)) predict neurological complications in sickle cell anaemia (SCA) but any association is unclear. In a cross-sectional study of 105 Kenyan children, mean CBFv was 120 +/- 34.9 cm/s; 3 had conditional CBFv (170-199 cm/s) but none had abnormal CBFv (>200 cm/s). After adjustment for age and haematocrit, CBFv > or =150 cm/s was predicted by SpO(2) < or = 95% and history of fever. Four years later, 10 children were lost to follow-up, none had suffered neurological events and 11/95 (12%) had died, predicted by history of fever but not low SpO(2). Natural history of SCA in Africa may be different from North America and Europe.
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International Paediatric Stroke Study: stroke associated with cardiac disorders.
Int J Stroke
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The aetiologies of arterial ischaemic stroke in children are diverse and often multifactorial. A large proportion occurs in children with cardiac disorders. We hypothesized that the clinical and radiographic features of children with arterial ischaemic stroke attributed to cardiac disorders would differ from those with other causes.
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Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study.
Ann. Neurol.
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Previous studies in adults and mice have implicated ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also known as von Willebrand factor (VWF)-cleaving protease, as a protective factor for stroke. Here we investigated ADAMTS13 in 208 pediatric patients with arterial ischemic stroke (AIS) and 125 population-based control children in a frequency-matched case-control study.
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Sickle cell anemia: iron availability and nocturnal oximetry.
J Clin Sleep Med
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To test the hypothesis that low iron availability, measured as transferrin saturation, is associated with low nocturnal hemoglobin oxygen saturation (SpO(2)) in children with homozygous sickle cell anemia (SCA; hemoglobin SS).
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Stability of polysomnography for one year and longer in children with sickle cell disease.
J Clin Sleep Med
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Serious morbidity may be linked to sleep disordered breathing (SDB) among children with sickle cell disease (SCD). We investigated the stability of polysomnography (PSG) results among children not having acute complications of SCD.
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Enuresis associated with sleep disordered breathing in children with sickle cell anemia.
J. Urol.
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Enuresis and sleep disordered breathing are common among children with sickle cell anemia. We evaluated whether enuresis is associated with sleep disordered breathing in children with sickle cell anemia.
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Transsylvian selective amygdalohippocampectomy in children with hippocampal sclerosis: seizure, intellectual and memory outcome.
Seizure
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This study investigates the efficacy of transylvian selective amygdalohippocampectomy (TS SAH) in children with medically intractable epilepsy due to unilateral hippocampal sclerosis. Post-surgical seizure control, intellectual and memory outcomes are examined.
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Precursors of executive function in infants with sickle cell anemia.
J. Child Neurol.
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Executive dysfunction occurs in sickle cell anemia, but there are few early data. Infants with sickle cell anemia (n = 14) and controls (n = 14) performed the "A-not-B" and Object Retrieval search tasks, measuring precursors of executive function at 9 and 12 months. Significant group differences were not found. However, for the A-not-B task, 7 of 11 sickle cell anemia infants scored in the lower 2 performance categories at 9 months, but only 1 at 12 months (P = .024); controls obtained scores at 12 months that were statistically comparable to the scores they had already obtained at 9 months. On the Object Retrieval task, 9- and 12-month controls showed comparable scores, whereas infants with sickle cell anemia continued to improve (P = .027); at 9 months, those with lower hemoglobin oxygen saturation passed fewer trials (R s = 0.670, P = .024) and took longer to obtain the toy (R s = -0.664, P = .013). Subtle delays in acquiring developmental skills may underlie abnormal executive function in childhood.
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Interrater reliability of Engel, International League Against Epilepsy, and McHugh seizure outcome classifications following vagus nerve stimulator implantation.
J Neurosurg Pediatr
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Interrater reliability as measured by the kappa (?) statistic is a widely used and valuable tool to measure the robustness of a scoring system. Seizure frequency reduction is a central outcome measure following vagus nerve stimulation (VNS). A specific VNS scoring system has been proposed by McHugh, but its interrater reliability has not been tested. The authors assessed its interrater reliability and compared it with that of the Engel and International League Against Epilepsy (ILAE) systems.
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Peripheral vascular response to inspiratory breath hold in paediatric homozygous sickle cell disease.
Exp. Physiol.
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There is increasing evidence that autonomic dysfunction in adults with homozygous sickle cell (haemoglobin SS) disease is associated with enhanced autonomic nervous system-mediated control of microvascular perfusion. However, it is unclear whether such differences are detectable in children with SS disease. We studied 65 children with SS disease [38 boys; median age 7.2 (interquartile range 5.1-10.6) years] and 20 control children without symptoms of SS disease [8 boys; 8.7 (5.5-10.8) years] and recorded mean arterial blood pressure (ABP) and daytime haemoglobin oxygen saturation (S(pO(2))). Cutaneous blood flux at rest (RBF) and during the sympathetically activated vasoconstrictor response to inspiratory breath hold (IBH) were measured in the finger pulp of the non-dominant hand using laser Doppler fluximetry. Local factors mediating flow motion were assessed by power spectral density analysis of the oscillatory components of the laser Doppler signal. The RBF measured across the two study groups was negatively associated with age (r = -0.25, P < 0.0001), ABP (r = -0.27, P = 0.02) and daytime S(pO(2)) (r = -0.30, P = 0.005). Children with SS disease had a higher RBF (P = 0.005) and enhanced vasoconstrictor response to IBH (P = 0.002) compared with control children. In children with SS disease, higher RBF was associated with an increase in the sympathetic interval (r = -0.28, P = 0.022). The SS disease status, daytime S(pO(2)) and age explained 22% of the variance in vasoconstrictor response to IBH (P < 0.0001). Our findings suggest that blood flow and blood flow responses in the skin of young African children with SS disease differ from those of healthy control children, with increased resting peripheral blood flow and increased sympathetic stimulation from a young age in SS disease. They further suggest that the laser Doppler flowmetry technique with inspiratory breath hold manoeuvre appears to be robust for use in young children with SS disease, to explore interactions between S(pO(2)), ABP and autonomic function with clinical complications, e.g. skin ulceration.
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Seizures in 204 comatose children: incidence and outcome.
Intensive Care Med
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Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain.
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Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis.
BMJ Open
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Recent changes in malaria transmission have likely altered the aetiology and outcome of childhood coma in sub-Saharan Africa. The authors conducted this study to examine change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood non-traumatic coma over a 6-year period.
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Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia.
Blood
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Silent cerebral infarct (SCI) is the most common form of neurologic disease in children with sickle cell anemia (SCA). SCI is defined as abnormal magnetic resonance imaging (MRI) of the brain in the setting of a normal neurologic examination without a history or physical findings associated with an overt stroke. SCI occurs in 27% of this population before their sixth, and 37% by their 14th birthdays. In adults with SCA, the clinical history of SCI is poorly defined, although recent evidence suggests that they too may have ongoing risk of progressive injury. Risk factors for SCI include male sex, lower baseline hemoglobin concentration, higher baseline systolic blood pressure, and previous seizures. Specific morbidity associated with SCI includes a decrement in general intellectual abilities, poor academic achievement, progression to overt stroke, and progressive SCI. In addition, children with previous stroke continue to have both overt strokes and new SCI despite receiving regular blood transfusion therapy for secondary stroke prevention. Studies that only include overt stroke as a measure of CNS injury significantly underestimate the total cerebral injury burden in this population. In this review, we describe the epidemiology, natural history, morbidity, medical management, and potential therapeutic options for SCI in SCA.
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Continuous EEG monitoring in Kenyan children with non-traumatic coma.
Arch. Dis. Child.
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The aim of this study was to describe the EEG and clinical profile of seizures in children with non-traumatic coma, compare seizure detection by clinical observations with that by continuous EEG, and relate EEG features to outcome.
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