Ischemic Perinatal Stroke: Summary of a Workshop Sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke (original) (raw)

New insights (and new interrogations) in perinatal arterial ischemic stroke

Thrombosis Research, 2011

With an incidence of 1/2800 to 1/5000 live-births, perinatal arterial ischemic stroke is the most frequent form of cerebral infarction in children. About 40% of the children do not have specific symptoms in the neonatal period, and are only recognized later with the emergence of motor impairment, developmental delay, specific cognitive deficiency or seizures. In the remaining 60%, children present with early symptoms, mostly recurrent focal seizures in the first 3 days of life. The diagnosis is easily confirmed by cranial ultrasounds and MRI. Early MRI has both a key role in the diagnosis, dating the injury, but also an important prognostic value to predict the motor outcome of the child. Indeed, although the infarct does not recur, the majority of children show subsequent sequels: cerebral palsy, epilepsy, cognitive or behavioural problems. Finding predictors of outcome regarding these latter concerns (and the way to prevent or alleviate them) is of major interest. The main etiological hypothesis for perinatal AIS is a cerebral embolus, originating from the placenta through the foramen ovale. Most of the established risk factors are indeed either determinants or biomarkers of vasculo-placental pathology. Injury to the cervico-cerebral arteries, giving rise to thrombus/embolus during the birthing process is also suggested. Both placento-embolic and traumatic theories are supported by a few, but well-analysed pathological or arteriographic reports. Nevertheless, their relative frequency, the implication of other mechanisms, and their repercussions to evidence-based preventive strategies remain to be determined. Moreover, the mechanism of stroke in the different groups of newborns with stroke (term vs. preterm; symptomatic neonates vs. those with a delayed presentation) is likely to be different, and there is a need for future studies to assess all populations as different entities. Neonatal supportive care remains important for all infants while there is no evidence for preventive anticoagulant use at present. In an effort to reduce neurological dysfunction, and in adjunction with ongoing physical therapy and pharmacological treatment, new rehabilitative interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used.

Diagnosis of perinatal stroke II: mechanisms and clinical phenotypes

Acta Paediatrica, 2009

Introduction: Here (and in an accompanying article dealing with definitions, differential diagnosis and registration), a structured sequential diagnostic flow is proposed to discern clinical phenotypes for perinatal stroke, including arterial ischaemic stroke (AIS), cerebral sinovenous thrombosis (CSVT) and haemorrhagic stroke. Material and results: For neonatal AIS, the diagnostic sequence is infection, trauma, embolism, arteriopathy, other, primary thrombosis and unclassifiable; for neonatal CSVT, the sequence is infection, trauma, venopathy, other, primary thrombosis and unclassifiable. The proposed hierarchical diagnostic flows are an initial step towards a standard for registration of the causes of neonatal stroke. Such standardization should guide attempts at prevention and intervention. An extensive literature search and study of a retrospective cohort of 134 newborn infants with stroke suggest that embolism is the most common identifiable cause for stroke in general (25%), preceding trauma (10%) and infection (8%). Other causes, such as asphyxia, acute blood loss, extracorporeal membrane oxygenation, genetic disorders or prothrombotic conditions, are seen in <5% of cases. For neonatal AIS, the presence of an embolic phenotype is 33% in this cohort. The designation unclassifiable scored 34% for the entire stroke group and 25% for neonatal AIS. Complex arterial stroke with multiple arteries involved is often seen when the underlying cause is infection, cranial trauma or embolism. One important conclusion is that a means of prevention is avoidance of embolism from thrombosis outside the brain.

Acutely and Retrospectively Diagnosed Perinatal Stroke: A Population-Based Study

Stroke, 2007

Background and Purpose-There are not very many epidemiological studies on perinatal stroke, and many authors suggest that this may be an underdiagnosed condition. The aim of the study was to estimate the incidence of perinatal arterial ischemic and hemorrhagic stroke in Estonia, to study the first clinical signs and to identify possible differences in predisposing factors and outcome between acutely and retrospectively diagnosed cases of perinatal stroke. Methods-A retro-and prospective study of acutely (within the first month) and retrospectively diagnosed ischemic and hemorrhagic cases of perinatal stroke was conducted in a children population born in the eastern and southern regions of Estonia during the years 1994 to 2003. Patients were identified from a pilot study, hospital records, and an inquiry of child neurologists and general practitioners. The diagnosis was confirmed in 38 (12 were diagnosed acutely and 26 retrospectively) cases by neuroradiology (MRI or CT). Results-The incidence rate of perinatal stroke in Estonia is 63 per 100 000 live births. Main clinical findings in the neonatal period were seizures, abnormalities of muscular tone, and disturbed level of alertness. Previously identified risk factors occurred in 32% of cases. Children with early diagnosis had more often adverse events during pregnancy and delivery (PϽ0.05) and developed more severe stage of hemiparesis compared with children with late diagnosis (PϽ0.05). Conclusions-The incidence rate of 63 per 100 000 live birth is higher than previously reported. Detailed analysis of the first signs of perinatal stroke may improve the early diagnostics of perinatal stroke.

Acutely and Retrospectively Diagnosed Perinatal Stroke

Stroke, 2007

Background and Purpose— There are not very many epidemiological studies on perinatal stroke, and many authors suggest that this may be an underdiagnosed condition. The aim of the study was to estimate the incidence of perinatal arterial ischemic and hemorrhagic stroke in Estonia, to study the first clinical signs and to identify possible differences in predisposing factors and outcome between acutely and retrospectively diagnosed cases of perinatal stroke. Methods— A retro- and prospective study of acutely (within the first month) and retrospectively diagnosed ischemic and hemorrhagic cases of perinatal stroke was conducted in a children population born in the eastern and southern regions of Estonia during the years 1994 to 2003. Patients were identified from a pilot study, hospital records, and an inquiry of child neurologists and general practitioners. The diagnosis was confirmed in 38 (12 were diagnosed acutely and 26 retrospectively) cases by neuroradiology (MRI or CT). Results—...

Perinatal arterial ischaemic stroke: an update with literature review

JPMA. The Journal of the Pakistan Medical Association, 2008

Perinatal arterial ischaemic strokes are a major cause of morbidity in the neonatal period and leads to significant neurological morbidity. It is however under recognized as an entity and usually missed till the baby is 3-4 months of age when they first present with hemiplegia. Perinatal arterial ischaemic strokes are not reported from our country and this may be due to the fact that neurodiagnostic modalities were not available until the last few years. Even now this is not available in the smaller cities of our country. In this review we will discuss the common issues related to etiology and pathogenesis in perinatal arterial ischaemic stroke. The management and the prognosis are also reviewed especially discussing the factors that affect the long term prognosis.

Risk Factors for Perinatal Arterial Stroke: A Study of 60 Mother-Child Pairs

Pediatric Neurology, 2007

The objective of the present study was to examine demographic, historical, and prothrombotic risk factors in infants with perinatal arterial stroke and their mothers. Risk factors were evaluated in 60 motherchild pairs with perinatal arterial stroke. Prothrombotic factors analyzed included the DNA mutations factor V Leiden, prothrombin 20210, MTHFR C677T and A1298C; serum activity levels for protein C, protein S, and antithrombin III; serum levels of lipoprotein(a); and, in the mothers, antiphospholipid antibodies. Boys predominated, 36:24. There were four twin sets. Sixty percent were term and 22% were postdate. Ten were large for gestational age. Five mothers had abdominal trauma. Nine mothers (15%) had preeclampsia. Emergency caesarean section was performed in 17 cases (28%). Eight placental exams revealed seven with abnormalities. Seizures were the presenting sign in 70%, and 30% presented with early handedness or cerebral palsy. Prothrombotic risk factors were found in 28 of 51 mothers (55%) and 30 of 60 children (50%). Forty-one pairs (68%) had at least one abnormality in mother, child, or both. Long-term sequelae included cerebral palsy (40 of 51; 78%), cognitive impairment (35 of 51; 68%), seizures (23 of 51; 45%), and microcephaly (26 of 51; 51%). Perinatal arterial stroke is the result of multifactorial, synergistic fetal and maternal factors among which the prothrombotic factors, both fetal and maternal, appear significant.

Workup for Perinatal Stroke Does Not Predict Recurrence

Stroke

P erinatal ischemic stroke is the most common presentation of pediatric stroke. 1 Perinatal ischemic stroke is defined as a focal disruption of cerebral blood flow secondary to arterial or cerebral venous thrombosis or embolization, between 20 weeks of fetal life through 28th postnatal day, confirmed by neuroimaging. 2 Thus, perinatal ischemic stroke occurs in the prenatal, birth, or postnatal time periods. Clinical presentation from birth to 28 days of life is termed neonatal stroke, while presentation later in life is called presumed perinatal stroke. Risk factors that have been associated with cases of ischemic perinatal stroke can be divided into maternal, placental, and fetal. Maternal risk factors include thrombophilia, infertility, prolonged rupture of membranes, preeclampsia, smoking, intrauterine growth restriction, and infection. 1,3-6 The placental risk factors include chorioamnionitis, placental infarcts, and placental weight less than the 10th percentile. 7 Fetal risk factors include thrombophilia, congenital heart disease, and arteriopathy. 6,8-10 The roles of fetal risk factors, including thrombophilia, arteriopathy, and cardioembolic risk factors, in the pathogenesis of perinatal ischemic stroke or recurrence risk are unclear. Thrombophilia has been associated with perinatal ischemic stroke, including deficiencies in antithrombin, protein C, protein S, factor V Leiden, and prothrombin gene mutation G20210A, as well as with elevations in homocysteine and lipoprotein (a) and positive antiphospholipid antibodies. 11-14 Limited by their retrospective, multicenter approach, these studies compile data from varied laboratory panels with inconsistent definitions of abnormal thrombophilia testing. Recent evaluation of 135 patients and 77 controls found no increase in thrombophilia in children after perinatal stroke. 15 However, this study did not assess risk factors for recurrent stroke after perinatal stroke. Arteriopathy is rarely reported in perinatal arterial ischemic stroke, except for 1 case report of an arterial dissection. 8 Congenital heart disease is associated with perinatal arterial Background and Purpose-Perinatal stroke, including neonatal and presumed perinatal presentation, represents the age in childhood in which stroke occurs most frequently. The roles of thrombophilia, arteriopathy, and cardiac anomalies in perinatal ischemic stroke are currently unclear. We took a uniform approach to perinatal ischemic stroke evaluation to study these risk factors and their association with recurrent stroke. Methods-We reviewed records of perinatal stroke patients evaluated from August 2008 to February 2016 at a single referral center. Demographics, echocardiography, arterial imaging, and thrombophilia testing were collected. Statistical analysis was performed using Fisher exact test. Results-Across 215 cases, the median follow-up was 3.17 years (1.49, 6.46). Females comprised 42.8% of cases. Age of presentation was neonatal (110, 51.2%) or presumed perinatal (105, 48.8%). The median age at diagnosis was 2.9 days (interquartile range, 2.0-9.9) for neonatal stroke and 12.9 months (interquartile range, 8.7-32.8) for presumed perinatal stroke. Strokes were classified as arterial (149, 69.3%), venous (60, 27.9%), both (4, 1.9%), or uncertain (2, 0.9%) by consensus imaging review. Of the 215 cases, there were 6 (2.8%) recurrent ischemic cerebrovascular events. Abnormal thrombophilia testing was not associated with recurrent stroke, except for a single patient with combined antithrombin deficiency and protein C deficiency. After excluding venous events, 155 patients were evaluated for arteriopathy and cardioembolic risk factors; neither was associated with recurrent stroke. Positive family history of thrombosis was not predictive of abnormal thrombophilia testing. Conclusions-Thrombophilia, arteriopathy, or cardioembolic risk factors were not predictive of recurrent events after perinatal stroke. Thrombophilia evaluation in perinatal stroke should only rarely be considered.