Table of Contents
Washington University Experience | VASCULAR | Hypoxia-Ischemia, fetal-neonatal | White Matter | 10A0 Case 1 History
Case 10 History ---- The deceased was a 49-day-old, former 34-week gestation male infant with fetal hydrops, massive hepatosplenomegaly, and hepatic and renal failure with APGARs of 1 (1 min), 6 (5 min) and 6 (10 min). A sibling had previously died in utero in 2011 with similar findings. The baby was delivered 4/20 via emergent cesarean section for nonreassuring biophysical profile and was hydropic with ascites at birth. The differential diagnosis included giant cell hepatitis, congenital CMV, and autoimmune hepatitis. Due to concern for potential gestational alloimmune liver disease, he was given 3 doses of IVIG. Core biopsy was interpreted as consistent with hemophagocytic lymphohistiocytosis (HLH), prompting genetic studies which identified a UNC13D mutation. Ultrasound performed on the day of birth demonstrated germinal matrix hemorrhage Grade 1 and repeat sonogram (on 5/8) confirmed periventricular parenchymal tissue loss. Subsequent brain MRI (5/18) found diffuse periventricular cystic areas of encephalomalacia with punctate internal calcifications, areas of hemorrhage, diffuse white matter loss, and a small cerebellum and medulla. He also had renal parenchymal disease, muscular VSD, and pulmonary hypoplasia with respiratory failure, hypothyroidism, and pancytopenia. Subsequent evaluation was concerning for extensive hepatic fibrosis and diffuse CNS injury. Throughout hospitalization, he remained in critical condition, with worsening ascites progressing to anasarca and the development of cholestatic hepatitis which progressed to neonatal liver failure (INR >2). On 6/8, he developed metabolic acidosis, bradycardia, and necrotizing enterocolitis unresponsive to fluids, pressors, and antibiotics. He expired on 6/8 due to enterococcus faecalis sepsis. ---- Autopsy findings included intraventricular clot as well as extensive, subacute; cystic/cavitating encephalomalacia, chiefly involving white matter, mineralized neurons in the basal ganglia and thalamus, and hydrocephalus. The neuropathology in this case is most consistent with both intraventicular hemorrhage and parenchymal hypoxic/ischemic damage in a premature infant; however, this child was born at 34 weeks, a time later that most periventricular white matter damage occurs. Later in gestation, damage typically involves more gray matter pathology which may explain the thalamic mineralized neurons in this case. An ultrasound taken on the same day as birth showed evidence of germinal matrix hemorrhage and adjacent abnormal parenchyma, confirmed by MRI some time later. The presence of APGARs of 1, 6, and 6 at 1, 5 and 10 minutes, respectively, and little crying at birth suggest significant CNS damage may have existed at the time of birth. It seems probable some of the pathology in this case may reflect intrauterine insults.
