Clinical and radiological recurrence after childhood arterial ischemic stroke

Background: Data on rates and risk factors for clinical and radiological recurrence of childhood arterial ischemic stroke (AIS) might inform secondary prevention strategies. Methods and Results: Consecutive Great Ormond Street Hospital patients with first AIS were identified retrospectively (1978–1990) and prospectively (1990–2000). Patients underwent repeat neuroimaging at the time of clinical recurrence or, if asymptomatic, at least 1 year after AIS. Cox and logistic regression analyses were used to explore the relationships between risk factors and clinical and radiological recurrence, respectively. A total of 212 patients were identified, of whom 97 had another prior diagnosis. Seventy-nine children had a clinical recurrence (29 strokes, 46 transient ischemic attacks [TIAs], 4 deaths with reinfarction 1 day to 11.5 years (median 267 days) later); after 5 years, 59% (95% confidence interval, 51% to 67%) were recurrence free. Moyamoya on angiography and low birth weight were independently associated with clinical recurrence in the whole group. Genetic thrombophilia was associated with clinical recurrence in previously healthy patients, independent of the presence of moyamoya. Sixty of 179 patients who had repeat neuroimaging had radiological reinfarction, which was clinically silent in 20. Previous TIA, bilateral infarction, prior diagnosis (specifically immunodeficiency), and leukocytosis were independently associated with reinfarction. Previous TIA and leukocytosis were also independently associated with clinically silent reinfarction. Conclusions: Clinical and radiological recurrence are common after childhood AIS. The risk of clinical recurrence is increased in children with moyamoya and, in previously healthy patients, in those with genetic thrombophilia. Preexisting pathology, including immunodeficiency, and persistent leukocytosis are risk factors for radiological recurrence, which suggests a potential role for chronic infection

American Society of Hematology 2020 guidelines for sickle cell disease: Prevention, diagnosis, and treatment of cerebrovascular disease in children and adults

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan.OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD.METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations.RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings.CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.</p

Recognition and prevention of neurological complications in pediatric cardiac surgery

Because of advances in surgical and cardiopulmonary bypass techniques it is now possible to definitively repair the vast majority of congenital heart disease in infancy or childhood. Although the majority of survivors do not have obvious cerebral sequelae, there is increasing disquiet about the high incidence of acute neurological events in the immediated postoperative period as well as evidence that at long-term follow-up there are subtle cognitive and motor deficits in many. Some children are more at risk of neurodevelopmental problems, either because of their cardiac (e.g., extensive aortopulmonary collaterals) or cerebrovascular (e.g., the propensity to large vessel dissection) anatomy or because of genetic predisposition (e.g., to prothrombotic disorders). The incidence may vary with the surgery (e.g., the Fontan operation) and the cardiopulmonary bypass technique necessary to achieve an adequate technical repair (e.g., low or no flow at deep hypothermia). Recognition of the population at risk will lead to prevention of serious sequelae. Data collected in adults may be misleading, and many pediatric units have developed their own practice, but recent studies in animal models of child surgery and in children have produced some evidence to guide management to ensure the optimal cerebral as well as cardiac outcome. Pump flow should be maintained at least 30 ml/kg/min where possible, with inotropic support to maintain blood pressure if necessary. If pump flow must be lowered or circulatory arrest is essential, thorough cerebral cooling to deep hypothermic temperatures is mandatory; a pH-stat strategy may make this easier, but an α-stat strategy may be better in those operations that can be performed at moderate hypothermia. There is no evidence that the available pulsatile pumps offer an advantage. Tissue oxygenation may reach critical levels and a high hematocrit and oxygen tension may reduce the risk of significant hypoxia. There is a risk of embolization in children, which can be reduced with membrane oxygenators and careful monitoring; the role of arterial filtration remains controversial. The only protective agent that can currently be recommended is methylprednisolone to protect the spinal cord (e.g., in operations on the aortic arch). Further studies are needed in this important area.</p

Acute neurology

The importance of thorough clinical examination of the child who presents with acute neurological problems is emphasized. A number of new diagnostic techniques are available, most of which are relatively non-invasive. The recent investigative advances may play a part in exposing the pathology underlying stroke, trauma or coma and in guiding management, which needs to be carefully tailored to the individual child's condition

Stroke in childhood

Presentation with stroke is rare in children, with an incidence of 2.6 and 3.1/100 0000 white and black children, respectively.1 Half are haemorrhagic, requiring immediate transfer to a neurosurgical unit in case decompression is required. Traditionally, ischaemic strokes have been considered to be idiopathic and to have a good prognosis, with a low recurrence risk and good recovery of motor function and school performance. They have not been investigated extensively, on the basis that management would not alter. However, there is a significant mortality,1 as well as considerable morbidity and a risk of recurrence, none of which has been adequately defined epidemiologically. In addition, there is now evidence that the neurological outcome could be improved, at least in some subgroups, by appropriate emergency management and, particularly, that recurrence might be preventable. This article proposes essential investigations and management for “good practice” in the current state of knowledge, although further research is clearly required before evidence based guidelines can be produced

Characteristics of children with underlying cardiac defects who developed Arterial Ischaemic Stroke (IS)

Background: Cardiac disease is a common underlying condition in children with arterial ischemic stroke (AIS). Embolism, dissection and moyamoya are recognised mechanisms and iron deficiency has been associated. However, few recent data exist relating the nature of the underlying cardiac defects, or associations withrecent investigational or surgical proceduresObjective: To investigate characteristics of children with underlying cardiac defects who developed AIS.Method: Review of cardiac cases from Great Ormond Street first AIS cohort presenting 1978-2000.Results: Of 212 with AIS, 33 (16%) children had underlying cardiac disease, with more boys (23; 70%). Median age at presentation was 4.7 (range 0.6-16.3) years. 17 (52%) developed stroke following cardiac surgery, 1 following catheterisation and15 (49%) spontaneously. 6 had another diagnosis (skin haemangioma, linear sebaceous naevus, Down syndrome, Williams syndrome, acute lympoblastic leukaemia and immunodeficiency). The majority had right sided cerebral infarction (49%) followed by left side (30%) and bilateral (21%). Anterior (n=30) was commoner than posterior circulation involvement (n=3). Cerebral infarction was purely subcortical in 8, purely cortical in 7, and involved both cortical and subcortical tissue in 18 children. 20 (60%) had arterial imaging which showed occlusion in 7, stenosis in 4, dissection in 2, moyamoya in 2 and normal vessels in 5. 6 (16%) died following stroke, 6 (16%) had recurrent stroke, and 4 (11%) had further transient ischaemic attacks. Seven (21%) had iron deficiency.Conclusion: Children with underlying cardiac defects comprised 1/6th of our AIS cohort; half had strokes spontaneously. Apparently primary cerebrovascular disease is as common as occlusion, presumably secondary to embolism. Iron deficiency was a risk factor in 1/5th but this and the other underlying diagnoses in addition to cardiac defects might increase the risk of developing AIS. This needs further investigation so that preventative strategies can be designed

Successful management of severe intracranial hypertension by surgical decompression

Because of the rather disappointing results in the treatment of acute head‐injury in adults, surgical decompression has been little used in the management of severe intracranial hypertension. The authors report the successful use of the technique for a child with encephalitis in whom cerebral perfusion was compromised. Traitement efficace de l'hypertension intracranienne majeure par décompression chirurgicale En raison des résultats décevants dans le traitement des traumatismes céphaliques aigus chez l'adulte, la décompression chirurgicale a été peu utilisée dans le traitement de l'hypertension intracranienne majeure. Les auteurs rapportent l'utilisation efficace de la technique chez un enfant porteur d'encéphalite don't l'irrigation cérébrale était compromise. Erfolgreiche Behandlung eines schweren intrakraniellen Hochdrucks durch chirurgische Dekompression Wegen der relativ enttäuschenden Ergebnisse bei der Behandlung akuter Kopfverletzungen bei Erwachsenen ist die chirurgische Dekompression bei schwerem intrakraniellem Hochdruck selten durchgeführt worden. Die Autoren berichten über die erfolgreiche Anwendung dieser Methode bei einem Kind mit Enzephalitis, bei dem die cerebrale Perfusion gefährdet war. Tratamiento con éxito de la hipertensión endocraneana severa por descompresión quirúrgica Debido a los resultados más bien decepcionantes obtenidos en la lesión craneal aguda en adultos, la descompresión quirúrgica se ha usado poco en el tratamiento de la hipertensiön intracraneal aguda grave. Los autorea aportan !a utilizatión con éxito de la técnica en un niño con encefalitis en que la perfusión cerebral estaba comprometida.</p

Risk factors for arterial ischemic stroke in childhood

Stroke affects up to 13 of 100,000 children, is more common in boys and African Americans, and is associated with considerable cognitive and psychiatric morbidity, as well as motor disability. Around half are hemorrhagic and half are ischemic. Underlying conditions include sickle cell disease, cardiac abnormalities, chromosomal abnormalities (eg, Down syndrome), and neurocutaneous conditions (eg, neurofibromatosis), but up to half the patients with ischemic stroke have no previously diagnosed condition. Although there is almost certainly an important genetic component to stroke risk, head trauma, infections, drugs and radiation appear to play an etiological role in some patients. The majority of the patients with infarction in an arterial distribution have associated cerebrovascular disease. Vascular pathologies include carotid or vertebrobasilar dissection, intracranial vasculopathy affecting the middle and anterior cerebral arteries, which is often transient, and moyamoya. Intermediate risk factors may include hypertension, hypoxia, and poor nutrition leading, for example, to iron deficiency and hyperhomocysteinemia. Some chronic conditions may directly influence the child's behavior and stroke recurrence risk, although large cohorts and randomized controlled trials will be needed before strategies for modification can be evidence-based

Case summary: Kate

After an uneventful birth and normal early milestones, Kate presented with infantile spasms at the age of seven months. Seizures terminated within two days of initiation of ACTH but her subsequent development was delayed. At two-and-a-half years of age she developed complex partial seizures that responded to carbamazepine monotherapy. The dosage was increased when she developed generalized tonic-clonic seizures and she is currently maintained on a maximal dose of a controlled release formulation. The EEG strongly supports the clinical diagnosis of complex partial seizures and an MRI shows a classical neuronal migration defect with gross band heterotopia throughout both cerebral hemispheres. She attends a school for children with moderate learning difficulties.</p

Noonan syndrome and moyamoya

We report a patient with Noonan syndrome and asymptomatic cardiac disease (supravalvular aortic stenosis and pulmonary valvular stenosis) who had frequent transient ischemic attacks. Bilateral moyamoya was evident; in addition, he manifested activated protein C resistance and was heterozygous for the factor V Leiden mutation. Anticoagulation abolished his episodes and, despite extensive cerebrovascular disease, he has no permanent neurologic deficits. The association between Noonan syndrome and moyamoya has not previously been described. Disruption of vascular development in prenatal life may have resulted in both cardiac and cerebrovascular disease in this child.</p