Biomedical subjects

Gabrielle Deveber

Publications and source records attributed to Gabrielle Deveber.

7 recordsLinked to original sources

PubMed2006

Astrocytic-inducible nitric oxide synthase in the ischemic developing human brain.

Variability in the expression of apoptotic and inflammatory mediators with time after an ischemic insult and their role in the expansion of cerebral infarcts are still controversial. This study examines DNA degradation and the expression of activated caspase-3 and iNOS, inducible nitric oxide (iNOS) in the human developing brain. Autopsy specimens from children with a neuropathologic diagnosis of focal ischemic infarct were included in the study. The specimens were classified based on the clinical history as acute (< 24 h, n = 5), subacute (24-72 h, n = 8), or old (> 72 h, n = 6) infarcts. Immunohistochemical staining for caspase-3, iNOS and TUNEL were then performed on all infarcts alongside age-matched controls. TUNEL staining was detected in regions of all infarcts. Expression of iNOS was significantly higher than that of caspase-3 in the penumbra of subacute infarcts (p = 0.02). Glial fibrillary acidic protein and iNOS staining co-localized in the penumbra of acute and subacute infarcts. These results suggest that cell death continues to occur for more than 3 d post ischemic insult. Cell death in the penumbra of subacute infarcts is partially caspase-3 independent and may be attributed to nitric oxide. Astrocytes are a source of iNOS and may play a role in the evolution of pediatric brain injury days after the initial insult.

Adolescent↗

PubMed2006

Diagnostic pitfalls in paediatric ischaemic stroke.

Diagnosing ischaemic stroke and determining its cause is difficult in children. Both are important for selection of treatment and prediction of outcome. This study explored the diagnostic changes that lead to a delay in the correct diagnosis of paediatric stroke. Case histories of 45 children with ischaemic stroke (31 males, 14 females; median age 6y; age range 2mo-16y) were retrospectively reviewed. The initial clinical diagnosis, based on the interpretation of presenting symptoms, was compared with the final aetiological stroke diagnosis after completion and review of diagnostic work-up. The type of diagnostic change, consequent time delay until correct diagnosis, reasons for change of diagnosis, and alterations to management were evaluated. Twenty-four diagnostic changes were identified; 19 in 'primary stroke diagnosis' (symptoms initially not attributed to stroke), and five in 'aetiological diagnosis' (incorrect initial determination of type or cause of stroke). The median interval between initial and final diagnosis was 7 days (3h-2y). The change in diagnosis led to therapeutic alterations in 17 patients. Risk factors for childhood stroke differ from those in adults. Stroke is frequently not recognized as the cause of the child's symptoms, and the correct determination of stroke aetiology takes time. We recommend that children with stroke be evaluated in a centre with expertize, using standardized diagnostic protocols and careful follow-up.

Adolescent↗

PubMed2006

Craniocervical arterial dissection in children: clinical and radiographic presentation and outcome.

Craniocervical arterial dissection is a recognized cause of arterial ischemic stroke in children. Whether children with craniocervical arterial dissection have dissection characteristics different from those of adults is unclear. A retrospective review of children, 1 month to 18 years of age, with dissection from two Canadian pediatric ischemic stroke registry centers was conducted. From 213 patients with arterial ischemic stroke, 16 (7.5%) were identified with dissection, 37.5% had warning symptoms, and 50% had a history of head or neck trauma. The clinical presentation included headache (44%), altered consciousness (25%), seizures (12.5%), and focal deficits (87.5%). Dissection involved extracranial vessels in 75% and anterior circulation in 56%. Follow-up included complete recovery in 43%, mild to moderate deficits in 44%, and severe deficits in 13%. Fourteen (87.5%) children received antithrombotic treatment. Follow-up angiography showed resolution of abnormalities in 60% of vessels. Total occlusion had the worst outcome for recanalization. In conclusion, the etiology of arterial dissection in the majority of children appears to be either trauma or idiopathic. Long-term angiography shows variable outcomes, depending on the initial findings. The relationship of angiographic outcomes with recurrent strokes requires further study in pediatric dissection. (J Child Neurol 2006;21:8-16).

Adolescent↗

PubMed2005

Prothrombotic abnormalities in childhood ischaemic stroke.

Childhood ischaemic stroke, incorporating arterial ischaemic stroke and cerebral sinus venous thrombosis, is associated with significant morbidity and mortality in children. The majority of cases in children present with well-recognised risk factors. The appreciation of the role prothrombotic abnormalities have in disease states is developing rapidly. Prothrombotic abnormalities are abnormalities of the coagulation system, fibrinolytic system, endothelial cells or platelets that lead to a reduced threshold for pathological thrombus formation. Our understanding of the role of prothrombotic abnormalities in childhood ischaemic stroke is increasing and has a direct bearing on the development of effective management and prevention strategies. We provide a brief background of prothrombotic abnormalities and review the available literature on prothrombotic markers in childhood ischaemic stroke. Overall, prothrombotic abnormalities have been identified in 20-50% of children presenting with AIS and 33-99% of children with cerebral sinus venous thrombosis. There appear to be a number of associations emerging including an increased frequency of factor V Leiden mutation, elevated lipoprotein (a), protein C deficiency and antiphospholipid antibodies in children presenting with arterial ischaemic stroke. The pathogenic role of prothrombotic abnormalities as predisposing to initial and recurrent childhood ischaemic stroke is becoming increasingly evident. The impact on treatment, however, will only be clarified with carefully designed, multi-institutional prospective studies.

Biomarkers↗

PubMed2005

Treatment and prevention of cerebrovascular disorders in children.

Cerebrovascular disorders are an important cause of mortality and chronic morbidity in children. Ischemic stroke is more common than cerebral venous thrombosis and hemorrhagic stroke in children. Several medical disorders have been associated with stroke in children, and a thorough evaluation of underlying causes is needed to determine the best treatment and prevention strategy. The treatment and prevention of stroke in children is not well studied, and current recommendations are based on adult studies, nonrandomized trials, or expert opinion. Children with stroke require immediate, special attention and if possible should be stabilized and transferred to an institution that can offer pediatric neurovascular expertise and care. All children with stroke should be referred to or have their care managed by a pediatric neurologist. The treatment of stroke in adults is well studied, and when applicable this evidence should be considered in the treatment of children with stroke. Data from animal and adult stroke studies have demonstrated a benefit for the aggressive treatment of infection, fever, blood pressure, hypo/hyperglycemia, intracranial pressure, and seizures, and should be applied to children with stroke. The use of thrombolytic, antithrombotic, and antiplatelet therapies is based on adult studies, cohort studies, and/or expert opinion. Two consensus guidelines regarding the treatment of arterial ischemic stroke and cerebral venous thrombosis were recently published and recommend the use of anticoagulants or antiplatelet agents in the acute setting, depending on the underlying cause of stroke. The evidence for the primary prevention of stroke in children is restricted to sickle cell disease (SCD) and derived from the Stroke Prevention in Sickle Cell Study Project studies. Long-term chronic transfusion therapy to maintain hemoglobin S levels below 30% is indicated in children with SCD and intracranial stenosis. It has also been recently determined that chronic transfusion therapy should not be stopped in children with SCD and an increased risk for stroke. The recurrence rate of arterial ischemic stroke (AIS) in children ranges from 6% to 30% and is highest among children with recurrent transient ischemic attack, cardiac disease, arteriopathies, and metabolic and coagulation abnormalities. Recommendations for secondary prevention are based on adult studies and the underlying pathophysiology of the stroke. Antiplatelet therapy (aspirin 1-5 mg/kg/day) is recommended in most children with a history of AIS. Although there is minimal evidence to support its use in children, anticoagulation may be indicated in AIS associated with extracranial arterial dissection, prothrombotic disorders, cardiac disease, severe intracranial stenosis, and recurrent AIS while on antiplatelet therapy.

Journal Article↗

PubMed2005

Preoperative and postoperative mapping of cerebrovascular reactivity in moyamoya disease by using blood oxygen level-dependent magnetic resonance imaging.

OBJECT: The ability to map cerebrovascular reactivity (CVR) at the tissue level in patients with moyamoya disease could have considerable impact on patient management, especially in guiding surgical intervention and assessing the effectiveness of surgical revascularization. This paper introduces a new noninvasive magnetic resonance (MR) imaging-based method to map CVR. Preoperative and postoperative results are reported in three cases to demonstrate the efficacy of this technique in assessing vascular reserve at the microvascular level. METHODS: Three patients with angiographically confirmed moyamoya disease were evaluated before and after surgical revascularization. Measurements of CVR were obtained by rapidly manipulating end-tidal PCO2 between hypercapnic and hypocapnic states during MR imaging. The CVR maps were then calculated by comparing the percentage of changes in MR signal with changes in end-tidal PCO2. Presurgical CVR maps showed distinct regions of positive and negative reactivity that correlated precisely with the vascular territories supplied by severely narrowed vessels. Postsurgical reactivity maps demonstrated improvement in the two patients with positive clinical outcome and no change in the patient in whom a failed superficial temporal artery-middle cerebral artery bypass was performed. CONCLUSIONS: Magnetic imaging-based CVR mapping during rapid manipulation of end-tidal PCO2 is an exciting new method for determining the location and extent of abnormal vascular reactivity secondary to proximal large-vessel stenoses in moyamoya disease. Although the study group is small, there seems to be considerable potential for guiding preoperative decisions and monitoring efficacy of surgical revascularization.

Adult↗

PubMed2004

Cerebrovascular disorders.

Arterial ischemic stroke is being recognized more commonly in the pediatric population. The etiologies differ greatly from those seen in adults. The most common etiologies are congenital heart disease and sickle cell disease. Children may present with or without hemiparesis and may have fever, headache, and depressed level of consciousness. A high index of suspicion is needed to diagnose stroke. Although clinical studies are scarce in children, besides early diagnosis, early specialized care with careful attention to detail ensuring adequate oxygenation and ventilation, prevention of hyperthermia and seizures, and maintenance of blood pressure and metabolic balance are important and likely improve outcome in these children. Selective children may also benefit from anticoagulant therapy, and, as the interval to diagnosis decreases, thrombolytic therapy may become an option although safety data are required. Children with acute stroke should be rapidly transported to and cared for in a pediatric center with a specialized stroke team or access to acute stroke protocols.

Adult↗