Perinatal arterial ischemic stroke.

Perinatal arterial ischemic stroke is a relatively common and serious neurologic disorder that can affect the fetus, the preterm, and the term-born infant. It carries significant long-term disabilities. Herein we describe the current understanding of its etiology, pathophysiology and classification, different presentations, and optimal early management. We discuss the role of different brain imaging modalities in defining the extent of lesions and the impact this has on the prediction of outcomes. In recent years there has been progress in treatments, making early diagnosis and the understanding of likely morbidities imperative. An overview is given of the range of possible outcomes and optimal approaches to follow-up and support for the child and their family in the light of present knowledge.

Congenital pial AVF along the falx cerebri with complete agenesis of the corpus callosum and bilateral parasagittal pachygyria-polymicrogyria secondary to chronic ischemia.

OBJECTIVE: Pial arteriovenous fistula (AVF) is an extremely rare entity due to direct arterial connection with the venous plexus without an intervening capillary network. The objective of this article is to describe a unique case of congenital pial AVF along the interhemispheric falx with complete callosal agenesis and malformation of cortical development within the bilateral anterior cerebral artery territories. We also demonstrated the distinctive feature of temporal stability of the extensive intracranial abnormalities without active intervention. Less than 100 cases have been reported thus far, most of which involve the adult rather than pediatric age group. A comprehensive literature review of congenital pial AVF will also be included. CASE DESCRIPTION: A 5-year-old child presented with headache and complex partial seizures. Imaging of the brain revealed the presence of polymicrogyria-pachygyria in the parasagittal frontoparietal lobes with associated underlying white matter hypodensities. Complete agenesis of the corpus callosum was also seen. In addition, enlarged and tortuous vessels were noted along the interhemispheric falx with no appreciable nidus. Bilateral dilated and tortuous ACAs were seen supplying the network of abnormal vessels along the falx. The radiological findings were stable on a follow-up MRI 12 years later. CONCLUSION: Our reported case adds to current limited knowledge of this rare entity in the pediatric age group, which is traditionally treated aggressively and urgently. Our case demonstrated temporal stability of this lesion with no detrimental complications observed. This suggests that the outcome of pial AVFs with conservative treatment may not be as grim as previously thought.

Aplasia Cutis Congenita with Ischemic Cortical Change and Normal Array Cytogenetic Analysis with a Fetus Papyraceus Twin.

BACKGROUND: Aplasia cutis congenita (ACC) is a heterogeneous condition that can be associated with fetus papyraceus. Few reports exist documenting genetic investigations in ACC or determining the etiology and recurrence risks. OBJECTIVE: We present a Frieden group 5 ACC with fetus papyraceus along with molecular studies. RESULTS: The newborn had multifocal aplasia cutis congenita involving the head, trunk, and limbs with cerebral ischemic changes demonstrated by imaging. The newborn had a monochorionic twin fetus papyraceus. The array cytogenetic analysis was normal. CONCLUSION: Supported by the ischemic cerebral damage, a monochorionic twin fetus papyraceus (monochorionic twins often have vascular anastomoses), and a normal cytogenetic array, this ACC with Frieden group 5 may have resulted from rapid but non-fatal exsanguination of the surviving twin into the dead twin. This type of ACC may have a low recurrence risk.

Low Apgar score, neonatal encephalopathy and epidural analgesia during labour: a Swedish registry-based study.

BACKGROUND: Maternal intrapartum fever (MF) is associated with neonatal sequelae, and women in labour who receive epidural analgesia (EA) are more likely to develop hyperthermia. The aims of this study were to investigate if EA and/or a diagnosis of MF were associated to adverse neonatal outcomes at a population level. METHODS: Population-based register study with data from the Swedish Birth Register and the Swedish National Patient Register, including all nulliparae (n=294,329) with singleton pregnancies who gave birth at term in Sweden 1999-2008. Neonatal outcomes analysed were Apgar score (AS)<7 at 5 min and ICD-10 diagnosis of neonatal encephalopathy (e.g. convulsions or neonatal cerebral ischaemia). Multivariate logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: EA was used in 44% of the deliveries. Low AS or encephalopathy was found in 1.26% and 0.39% of the children in the EA group compared with 0.80% and 0.29% in the control group. In multivariate analysis, EA was associated with increased risk with low AS, AOR 1.27 (95% CI 1.16-1.39), but not with diagnosis of encephalopathy, 1.11 (0.96-1.29). A diagnosis of MF was associated with increased risk for both low AS, 2.27 (1.71-3.02), and of neonatal encephalopathy, 1.97 (1.19-3.26). CONCLUSION: Diagnosis of MF was associated with low AS and neonatal encephalopathy, whereas EA was only associated with low AS and not with neonatal encephalopathy. The found associations might be a result of confounding by indication, which is difficult to assess in a registry-based population study.

Next generation biomarkers for brain injury.

In perinatal medicine, there is an emerging interest on the potential usefulness of non-invasive brain biochemical monitoring in infants at risk for brain injury. To date, several biomarkers such as neuro-proteins, calcium binding proteins, oxidative stress markers, vasoactive agents, inflammatory mediators, have been investigated. Results showed that hypoxia insult, under different conditions, triggers a biochemical pathophysiological cascade of events leading to brain damage. In this setting, increased biomarkers concentrations in different biological fluids have been found to correlate with the occurrence of brain damage at short-long term both in preterm and term fetuses/newborns. However, before inclusion of any biomarker in guidelines, USA and European institutions have recently stated a panel of criteria that have to be fulfilled. Therefore, the present review offers an overview of the main biomarkers currently studied in perinatal medicine and their progresses according to institutions' criteria.

Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes / Prenatal cerebrovascular accidents diagnosed in the early infant stage: a series of 10 patients

Introducción. El accidente cerebrovascular (ACV) fetal o prenatal se define como un suceso isquémico, trombótico o hemorrágico arterial o venoso que acontece entre las 14 semanas de gestación y el inicio del parto. Pacientes y métodos. Estudio retrospectivo de una serie de 10 pacientes afectos de un ictus, presumiblemente fetal, desapercibido durante el embarazo y diagnosticado en la etapa de lactante; se destacan cuáles han sido los síntomas y la edad en que se han identificado. Resultados. De los 10 pacientes estudiados, ninguno presentaba antecedentes maternos relevantes, pero se detectaron cuatro amenazas de parto pretérmino que se resolvieron con las medidas habituales y sin hallazgos de alteración fetal posterior. Entre el segundo y tercer trimestre de vida es cuando se han realizado los estudios que han llevado al diagnóstico, y se ha indicado por la familia una menor movilidad de un hemicuerpo respecto al contralateral como motivo de consulta. Dos pacientes presentaban una trombofilia. Con una media de seguimiento de seis años, todos asocian una parálisis cerebral infantil, la tercera parte una epilepsia y el 75% tiene dificultades de aprendizaje o discapacidad intelectual. Conclusión. Cuando los ACV no se detectan prenatalmente, es importante que en la atención primaria se busquen y detecten los signos de alarma del desarrollo psicomotor del lactante de forma precoz para iniciar su estudio y procurar una rehabilitación lo más pronto posible (AU)

Introduction. A foetal or prenatal cerebrovascular accident (CVA) is defined as an ischaemic, thrombotic or arterial or venous haemorrhagic event that occurs between the 14th week of gestation and the onset of labour. Patients and methods. We report a retrospective study of a series of 10 patients suffering from a, presumably foetal, stroke that went unnoticed during the pregnancy and was diagnosed in the early infant stage. The symptoms and the age at which they were identified are highlighted. Results. None of the 10 patients studied presented any relevant events in the mothers’ medical history, but there were four threats of a preterm birth that were solved using the usual means and without the occurrence of any alterations that later affected the foetus. The studies that led to the diagnosis were carried out between the sixth and ninth months of life, and the reason for visiting was reported by the family as being a lower degree of mobility on one side of the body with respect to the other. Two patients presented thrombophilia. With a mean follow-up time of six years, all the patients have an associated infantile cerebral palsy, a third of them have epilepsy and 75% have learning difficulties or intellectual disability. Conclusions. When CVA are not detected in the prenatal period, it is important in primary care to look for and detect the warning signs of the psychomotor development of the infant at an early stage in order to begin a study of the case and to undertake rehabilitation as early as possible (AU)

Severe cerebral injury in a recipient with twin anemia-polycythemia sequence.

Twin anemia-polycythemia sequence (TAPS) results from slow intertwin blood transfusion through minuscule placental vascular anastomoses and is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordance. The optimal management of TAPS is not clear. We report a case of TAPS detected antenatally by Doppler ultrasound examination at 15 + 6 weeks' gestation. After counseling, the parents opted for expectant management. Regular Doppler measurements were performed and these remained fairly stable. An emergency Cesarean section was performed at 34 + 5 weeks following signs of fetal distress. The donor twin was severely anemic while the recipient twin had severe polycythemia-hyperviscosity syndrome. On day 1, the recipient developed respiratory insufficiency and subclinical status epilepticus. Magnetic resonance imaging showed a total loss of gray-white matter differentiation as a sign of severe diffuse cerebral ischemia and bilateral intra- and extra-axial hemorrhages. There was almost complete lack of arterial and venous cerebral blood flow. On day 3 intensive care treatment was withdrawn in view of the severity of the brain injury. This case report demonstrates that TAPS may lead to severe cerebral injury and fatal outcome in the recipient twin, and highlights the importance of antenatal Doppler ultrasound monitoring and choice of management.

Acute onset antenatal fetal neurological injury suspected prenatally based on abnormalities in antenatal testing: a case report.

This report discusses the case of a fetus with previously normal findings of cardiotocograph that experienced an acute neurologic insult antenatally. The fetus presented with abnormalities of its heart rate tracing and its movement patterns on ultrasound. Following delivery, the infant was diagnosed with hypoxic ischemic encephalopathy by DWI in the first 24 h after birth, despite having a normal postnatal brain ultrasound.

Magnetic resonance imaging in cerebral ischemia: focus on neonates.

Magnetic resonance imaging (MRI) has dramatically changed our ability to diagnose and treat stroke as well as follow its evolution and response to treatment. Early stroke and ischemia can be visualized using diffusion-weighted imaging (DWI), which utilizes proton diffusion within tissues as a reporter for evolving neuropathology that reflects cytotoxic edema, particularly during the first several days after injury. Historically, T2-weighted imaging (T2WI) has been used for evaluation of vasogenic edema and also is a reliable indicator of injured tissue late after injury. While visual analysis of MR data can provide information about the evolution of injury, quantitative analyses allow definitive and objective evaluations of injury size and location and the effectiveness of novel therapeutic strategies. We review the clinical basis of imaging for stroke and ischemia diagnosis and the methods for post-processing of MR data that could provide novel insights into the evolution and pathophysiology of stroke in the newborn.

Neurological outcome of newborns with neonatal seizures: a cohort study in a tertiary university hospital.

OBJECTIVE: To describe the neurological outcome of newborns with seizures. METHOD: Cohort study with newborns prospectively followed. Perinatal characteristics and etiological screening were related to outcome in a regression model. RESULTS: During the study 3,659 newborns were admitted and 2.7% were diagnosed as having seizures. Hypoxic ischemic encephalopathy (51%) was the etiology more frequently associated to seizures and also to postneonatal epilepsy (53%). In the follow up 25 died during the acute neonatal illness and 9 during the first years of life, 19 were diagnosed as having post neonatal epilepsy, 35 had developmental delay and 11 an association among this two comorbidities. A significant association between abnormal postnatal EEG and neuroimaging to developmental delay (p=0.014, p=0.026) was observed. The group of newborns that had seizures presented an increased risk of developing epilepsy compared to newborns from the same cohort without seizures (19.3/100 vs. 1.8/100, p<0.001). CONCLUSION: In this study neonatal seizures predominated in term newborns with perinatal asphyxia an elevated perinatal mortality and post neonatal morbidity was observed. The follow up showed an increased risk for developing postnatal epilepsy and developmental delay.

Neurological outcome of newborns with neonatal seizures: a cohort study in a tertiary university hospital / Prognóstico neurológico de recém nascidos com crises convulsivas: estudo de coorte em hospital terciário

OBJECTIVE: To describe the neurological outcome of newborns with seizures. METHOD: Cohort study with newborns prospectively followed. Perinatal characteristics and etiological screening were related to outcome in a regression model. RESULTS: During the study 3659 newborns were admitted and 2.7 percent were diagnosed as having seizures. Hypoxic ischemic encephalopathy (51 percent) was the etiology more frequently associated to seizures and also to postneonatal epilepsy (53 percent). In the follow up 25 died during the acute neonatal illness and 9 during the first years of life, 19 were diagnosed as having post neonatal epilepsy, 35 had developmental delay and 11 an association among this two comorbidities. A significant association between abnormal postnatal EEG and neuroimaging to developmental delay (p=0.014, p=0.026) was observed. The group of newborns that had seizures presented an increased risk of developing epilepsy compared to newborns from the same cohort without seizures (19.3/100 vs. 1.8/100, p<0.001). CONCLUSION: In this study neonatal seizures predominated in term newborns with perinatal asphyxia an elevated perinatal mortality and post neonatal morbidity was observed.The follow up showed an increased risk for developing postnatal epilepsy and developmental delay.

OBJETIVO: Avaliar o prognóstico neurológico de neonatos com crises convulsivas. MÉTODO: Estudo prospectivo, realizado em coorte de neonatos provenientes de hospital terciário. As características clínicas perinatais e os resultados de exames complementares foram correlacionados com prognóstico através de modelo de regressão logística. RESULTADOS: Durante o estudo 3659 neonatos foram internados, sendo que 101 apresentaram crises convulsivas (2,7 por cento). A encefalopatia hipóxico-isquêmica foi a etiologia mais frequentemente associada às crises (51 por cento). O seguimento evidenciou 25 óbitos no período neonatal e 9 durante os primeiros anos de vida, 19 lactentes desenvolveram epilepsia, 35 atraso no desenvolvimento e 11 associação entre os dois desfechos. O modelo de regressão logística aplicado mostrou associação significativa entre EEG pós neonatal anormal e neuroimagem anormal com atraso no desenvolvimento (p=0,014, p=0,026). Os neonatos em estudo, quando comparados aos demais da mesma coorte, que não apresentaram crises convulsivas tiveram maior probabilidade de desenvolver epilepsia (19,3/100 vs. 1,8/100, p<0,001). CONCLUSÃO: Neste estudo em que ocorreu predomínio de crises neonatais em neonatos a termo com asfixia perinatal, foi observada alta mortalidade perinatal e morbidade. O seguimento neurológico evidenciou elevado risco de desenvolvimento de epilepsia e/ou atraso no desenvolvimento neuropsicomotor.

Ultrasonic assessment of cerebral blood flow changes during ischemia-reperfusion in 7-day-old rats.

A model of ischemic brain injury in 7-day-old rat pups has been developed to study perinatal ischemia. It combines permanent occlusion of the distal left middle cerebral artery (LMCA) and transient occlusion of homolateral common carotid artery (LCCA). At removal of the clip on LCCA, reflow allowed brain reperfusion through cortical anastomoses. In 10 rat pups, we measured blood flow velocities (BFV) in main cerebral arteries with 12-MHz ultrasound imaging. At basal states, peak systolic BFV in proximal LMCA was 16.0 +/- 3.0 cm.s(-1). Occlusion of LMCA did not yield significant modifications. Occlusion of LCCA involved only a decrease in BFV to 9.5 +/- 2.6 cm.s(-1) (p < 0.001). Indeed, LMCA was then supply by the right internal carotid and the vertebral arteries through the circle of Willis. In three rat pups, release of occlusion of LCCA was followed by restoration of BFV in the left internal carotid artery and in LMCA, in seven pups, by a reversed flow in the LICA and lower BFV in LMCA (11.9 +/- 2.3, p < 0.05). BFV returned to basal values from h5 to h48 in all animals. In addition, ultrasound imaging is a useful, reproducible, non invasive, easy-to-repeat, method to assess and monitor arterial cerebral blood flow supply in small animals. It helps to characterize changes occurring during cerebral ischemia and reperfusion, particularly the depth of the hypoperfusion, as well as the variability of reflow. In preclinical studies, this method could help to identify what can be assigned to a neuroprotective treatment and what depends on changes in cerebral blood flow supply.

Network injury to pulvinar with neonatal arterial ischemic stroke.

The purpose of this study is to establish that newborn stroke involving extensive parts of cerebral cortex immediately leads to secondary network injury in pulvinar. Seven term infants with cortical stroke presented with hypersignal in pulvinar on DWI. Stroke types included: complete MCA stroke (n=4); PCA stroke, ICA stroke and multiple artery stroke (1 each). Age range at scanning was between day 2 and 6 after birth (except for 1 infant scanned within 7 days of acute presentation during ECMO). ADC values in secondarily injured pulvinar were significantly higher than in the area with primary (sub)cortical injury (all patients scanned with identical MR image acquisition). In the absence of asphyxia and because pulvinar is outside of the primary area of infarction, we conclude that there are suggestions from imaging for acute secondary injury to pulvinar following primary damage of their cortical targets and/or connecting axons. Acute secondary injury is probably due to excitotoxicity and deafferentiation. The relevance of network injury for prognosis and the impact of early treatment on it have yet to be studied, in stroke but also in other acute perinatal brain disorders.

Unique anomalous origin of the left anterior cerebral artery.

We present the case of an anomalous origin of the left anterior cerebral artery (ACA) from the supraclinoid segment of the right internal carotid artery. Because of improved imaging quality, anomalies of the ACA-anterior communicating artery (AComA) complex are increasingly recognized on transaxial images. Although most of these anomalies are incidental findings of little clinical significance, some ACA-AComA complex anomalies are clinically significant. Recognition of these anomalies may be instrumental in developing a differential diagnosis or for improved surgical planning.

Hemorrhagic-ischemic cerebral injury in the preterm infant: current concepts.

PV-IVH and adjacent white matter injury remains a significant problem in the premature infant. The potential mechanisms contributing to injury are complex and involve factors related to blood flow and its regulation, as well as cellular mediators including cytokines, free radical formation, and excitotoxin release. Although a reduction in the occurrence of severe IVH can be achieved with indomethacin, it does translate into long-term neurodevelopmental benefit. This reinforces the concept of a more diffuse injury to brain in sick premature infants than is apparent from the appearance of current neuroimaging techniques.

Clinical manifestations of cerebrovascular hypoplasias in childhood.

The aim of the study was to analyze cerebrovascular hypoplasia in childhood and its clinical manifestations in a clinical population of 205 children aged 3 to 14 years. Cerebrovascular hypoplasias were diagnosed using angiography (n=63), magnetic resonance angiography, and transcranial Doppler ultrasonography. Hypoplasias were localized in the internal carotid artery in 41.9% of patients, in the middle cerebral artery in 54.1%, the anterior cerebral artery in 1.0%, and in the vertebro-basilar system in 3.0%. Clinical manifestations included transient ischemic attacks (21% of patients), cerebral infarcts (17%), progressive unilateral cerebral hemisphere atrophy (1.0%), focal and secondary generalized epileptic seizures (56.1%), and migraine-like headache (4.9%). Hypoplasias of the internal carotid artery and middle cerebral artery manifested as focal and secondary generalized epileptic seizures, transient ischemic attacks, cerebral infarcts, migraine-like headache, and progressive unilateral cerebral hemisphere atrophy, in descending order of frequency. Hypoplasias in the anterior cerebral artery or the basilar artery caused cerebral infarcts, and hypoplasias in the vertebral arteries caused transient ischemic attacks. This article discusses the pathophysiology of ischemia in the territory of the hypoplastic cerebral artery in childhood, as well as possibilities for noninvasive neuroimaging for diagnosis of cerebrovascular hypoplasias.

Antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants: prevalence and associated obstetric variables.

AIM: To assess the prevalence of an antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants; to identify possibly related obstetric risk factors. METHODS: A prospective cohort study was made of 1332 infants born at less than 34 completed weeks, using cranial ultrasound, for the presence of antenatal brain lesions (group A) involving the periventricular white matter (PVWM) or central grey matter. Entry criteria were presence of (i) cysts in the PVWM < 7 days; (ii) increased PVWM echogenicity < 6 hours, confirmed to be white matter necrosis at post mortem examination; (iii) a unilateral porencephalic cyst < 3 days; (iv) an intraventricular haemorrhage with unilateral parenchymal involvement < 6 hours; and (v) symmetrical areas of increased echogenicity in the thalami, confirmed to be areas of calcification on post mortem examination. Group B consisted of infants with a normal early neonatal ultrasound scan with subsequent development of the lesions mentioned above. RESULTS: Twenty four cases met the entry criteria for group A: 17 died and five of the seven survivors developed cerebral palsy at follow up. Of the whole cohort, 156 (11.7%) infants died and in 63 (40.3%) of these a large ultrasound lesion was present. In 17 (26.9%) cases this lesion was considered to be of antenatal onset. Sixty eight of the 1176 (5.8%) survivors developed cerebral palsy and this was attributed to antenatal onset in five (7.3%). A comparison of the obstetric risk factors between the infants in group A and B, who either died or developed cerebral palsy, showed a significant difference in gestational age between the two groups (30.9 vs 28.9 weeks; p < 0.001). Prolonged rupture of membranes was significantly more common in group B (p = 0.03), while an ominous cardiotachogram was significantly more common in group A (p = 0.01), and this remained significant following logistic regression analysis. CONCLUSIONS: Although these data suggest that most preterm infants did not develop their brain lesions in utero, an antenatal onset was not uncommon, especially in those with PVWM lesions, who did not survive the neonatal period.

Congenital erythroleukemia in a neonate with severe hypoxic ischemic encephalopathy.

We report a case of a neonate who presented with hypoxic ischemic encephalopathy, persistent hypoglycemia and hypotension, intractable metabolic acidosis, renal failure and a coagulopathy but who, at autopsy, was found to have massive infiltration of nonhematopoietic tissues with blasts. The diagnosis of congenital erythroleukemia was confirmed by the detection of glycophorin A, a major erythrocyte membrane protein, on the surface of the blasts. The clinical presentation and course of the case described here have not previously been reported for this extremely rare condition.

Arteriovenous malformation of the vein of Galen in three neonates: emphasis on associated early ischaemic brain damage.

UNLABELLED: Vein of Galen malformation is a rare intracranial disorder in newborns. In recent years the survival rate has improved due to improvement in endovascular treatment of this abnormality. We describe three neonates with a vein of Galen malformation for whom treatment was not attempted because of associated severe cerebral damage, of antenatal origin in two and of perinatal origin in the other. Autopsy was performed in two neonates. Periventricular leukomalacia was present in both cases, associated in one case with cortical infarction, gliosis and atrophy. CONCLUSION: We recommend careful evaluation of associated cerebral damage prior to attempted treatment of the vein of Galen malformation.

Central nervous system vasculopathy in neonatal lupus erythematosus.

Central nervous system involvement in neonatal lupus erythematosus (NLE) has not been previously reported. We report four patients with NLE, all with complete congenital heart block and three with cerebral ultrasound and color Doppler flow imaging (CDFI) studies demonstrating evidence of associated vasculopathy in the gangliothalamic vasculature. CDFI confirmed blood flow through the affected vessels, indicating that blood flow was not compromised at this early stage. Short-term follow-up revealed no signs of progression of the vasculopathy, focal ischemia, gangliothalamic atrophy, or neurological impairment. Nevertheless, the implications of this finding with respect to the natural history of NLE remain to be defined, particularly in cases in which the disease develops into systemic lupus erythematosus later in life. Besides specific diagnostic studies for NLE, cerebral ultrasound, and CDFI studies are mandatory in all cases of complete congenital heart block, regardless of whether mothers are diagnosed as having connective-tissue disease or not. Neonates with signs of vasculopathy in the gangliothalamic region should be examined for NLE.