Steven Schonfeld

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 ×g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; feto-placental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n= 537), or after a longer interval (n= 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born ≥1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8;p= 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9;p= 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

White matter disorders of prematurity: Association with intraventricular hemorrhage and ventriculomegaly

OBJECTIVES Because intraventricular hemorrhage (IVH) often precedes the development of sonographically defined white matter damage (WMD) in very preterm infants, we sought to identify the IVH characteristics that predict WMD. HYPOTHESES We evaluated variations on the null hypothesis that infants with IVH are no more likely than infants without IVH to have WMD. These variations dealt with characteristics of the IVH (presence or absence of ventriculomegaly) or characteristics of the WMD (size, localization, and laterality). METHODS A total of 1605 infants weighing 500 to 1500 g at birth between January 1991 and December 1993 underwent standardized cranial ultrasound studies with 6 standard coronal and 5 sagittal views at postnatal days 1 to 3, 7 to 10, and at 3 to 8 weeks. RESULTS A total of 129 (8%) infants had WMD, either an echodensity alone (n = 59), an echolucency alone (n = 18), or both (n = 52). In analyses that controlled for gestational age, IVH was associated with a fivefold to ninefold increased risk of WMD regardless of size, laterality, or extent of lesions (P </=.0005). Compared with infants with neither IVH nor ventriculomegaly, infants with both were at 18- to 29-fold greater risk of WMD (P </=.0005). CONCLUSIONS In this study IVH and ventriculomegaly were powerful predictors of WMD occurrence, whether small or large, unilateral or bilateral, localized or diffuse.

Topography of cerebral white-matter disease of prematurity studied prospectively in 1607 very-low-birthweight infants.

The objective of this study was to evaluate to what extent (1) the characteristics of localization, distribution, and size of echodense and echolucent abnormalities enable individuals to be designated as having either periventricular hemorrhagic infarction or periventricular leukomalacia and (2) the characteristics of periventricular hemorrhagic infarction and periventricular leukomalacia are independent occurrences. The population for this study consisted of 1607 infants with birthweights of 500 to 1500 g, born between January 1991 and December 1993, who had at least one cranial ultrasound scan read independently by at least two ultrasonographers. The ultrasound data collection form diagrammed six standard coronal views. The cerebrum was divided into 17 zones in each hemisphere. All abnormalities were described as being echodense or echolucent and were classified on the basis of their size, laterality, location, and evolution. Eight percent (134/1607) of infants had at least one white-matter abnormality. The prevalence of white-matter disease decreased with increasing gestational age. Most abnormalities were small or medium sized and unilateral; only large echodensities tended to be bilateral and asymmetric. Large abnormalities, whether echodense or echolucent, were more likely than smaller abnormalities to be widespread, and the extent of cerebral involvement was independent of whether abnormalities were unilateral or bilateral. Large abnormalities were relatively more likely than small abnormalities to involve anterior planes. Small abnormalities, whether echodense or echolucent, or whether unilateral or bilateral, preferentially occurred near the trigone. Using the characteristics of location, size, and laterality/symmetry, we were able to allocate only 53% of infants with white-matter abnormalities to periventricular hemorrhagic infarction or periventricular leukomalacia. Assuming that periventricular leukomalacia and periventricular hemorrhagic infarction are independent and do not share risk factors, and that each occurs in approximately 5% of infants, we would have expected 0.25%, or about 4 individuals, to have abnormalities with characteristics of both periventricular leukomalacia and periventricular hemorrhagic infarction, whereas we found 63 such infants. Most infants with white-matter disease could not be clearly designated as having periventricular hemorrhagic infarction or periventricular leukomalacia only. Periventricular hemorrhagic infarction contributes to the risk of periventricular leukomalacia occurrence, or the two sorts of abnormalities share common risk antecedent factors. The descriptive term echodense or echolucent and the generic term white-matter disease of prematurity should be used instead of periventricular leukomalacia or periventricular hemorrhagic infarction when referring to sonographically defined white-matter abnormalities. (J Child Neurol 2001;16:401-408).

Coarctation of the lateral ventricles: an alternative explanation for subependymal pseudocysts

Abstract Three cases of sonographically demonstrated cystic areas adjacent to the superolateral margins of the lateral ventricles are described. The cystic areas are considered secondary to a coarctation of the lateral ventricle, a normal variant. The cystic areas are not considered post-hemorrhagic or ischemic sequelae.

Digital subtraction angiography―a new approach to brain death determination in the newborn

The diagnosis of brain death in the newborn infants is elusive and often difficult. The lack of cerebral blood flow has become an identified criterion for loss of cerebral function. The diagnosis can be obtained by the technique of digital subtraction angiography, which is presented in two case reports demonstrating the utility of this technique.

Mechanical thrombectomy – is time still brain? The DAWN of a new era

Abstract Purpose: The purpose of this study is to review the history of treatments for acute ischemic stroke, examine developments in endovascular therapy, and discuss the future of the management of acute ischemic stroke. Methods: A selective review of recent clinical trials for the treatment of acute ischemic stroke was conducted. Results: We reviewed completed trials of the management of acute ischemic stroke including intravenous thrombolytics, intraarterial thrombolytics, and thrombectomy. We also assessed the future direction of research by reviewing ongoing clinical trials. Conclusions: The advancement of endovascular treatment for stroke has led to improved morbidity and mortality for patients. Future challenges include delivering these treatments to stroke centers worldwide.

Updates in the Management of Cerebral Infarctions and Subarachnoid Hemorrhage Secondary to Intracranial Arterial Dissection: A Systematic Review

OBJECTIVE Intracranial arterial dissection (IAD) is a rare cerebrovascular disease that is likely underdiagnosed because of the inherent difficulty of visualizing the subtle radiographic signs of the pathologic small intracranial arteries. No widespread consensus exists on the treatment of IAD, and thus it is often managed empirically because of the absence of major randomized controlled trials. In this study, we conducted a systematic review to evaluate the management and treatment options for IAD. METHODS We performed a systematic review in accordance with the PRISMA guidelines using the following databases: MEDLINE (PubMed) and Cochrane Library. Included studies were limited to human patients with dissections in intracranial vessels only. RESULTS A total of 82 studies were included in this systematic review. The most common complications of IAD were cerebral infarction and subarachnoid hemorrhage, and thus, patients with IAD can be subdivided into those presenting with either ischemia or hemorrhage, respectively. Those with ischemia were predominantly managed with antiplatelet therapy, whereas patients presenting with hemorrhage often were amenable to treatment with endovascular techniques. CONCLUSIONS Given these findings, clinicians should prescribe antiplatelet therapy for patients with IAD presenting with ischemia and consider endovascular treatment for those presenting with hemorrhage. However, further investigation is required given the heterogeneity of methods and reporting outcomes in the investigated studies.