Perinatal Arterial Ischemic Stroke in Fetal Vascular Malperfusion: A Case Series and Literature Review

Abstract

Fetal vascular malperfusion includes a continuum of placental histologic abnormalities increasingly associated with perinatal brain injury, namely arterial ischemic stroke. Here, we describe the clinical-neuroimaging features of 5 neonates with arterial ischemic stroke and histologically proved fetal vascular malperfusion. All infarcts involved the anterior territories and were multiple in 2 patients. In 2 neonates, there were additional signs of marked dural sinus congestion, thrombosis, or both. A mixed pattern of chronic hypoxic-ischemic encephalopathy and acute infarcts was noted in 1 patient at birth. Systemic cardiac or thrombotic complications were present in 2 patients. These peculiar clinical-radiologic patterns may suggest fetal vascular malperfusion and should raise the suspicion of this rare, underdiagnosed condition carrying important implications in patient management, medicolegal actions, and future pregnancy counseling.

FIG 1.

Brain MR imaging of patient 1 performed on day 1. Axial T1-weighted image (A), T2-weighted image (B), and ADC maps (C and D) demonstrate acute ischemic infarcts in the territory of the right MCA (arrowhead) and right anterior cerebral artery (ACA) (open arrow) associated with mild diffuse atrophy of this cerebral hemisphere as well as a late subacute infarct in the territory of the left MCA (arrow). In addition, there are signs of early secondary network injury of the right thalamus (asterisk) and splenium of the corpus callosum (black arrow) as well as subcortical and deep white matter injury and laminar cortical necrosis (small arrows). Axial T1-weighted image (E) and sagittal T2-weighted image (F) depict marked distension of the transverse and superior sagittal sinuses (arrows) with signs of slowing of the venous blood flow, confirmed on the coronal view of MRV (G). MRA (H) shows reduced visualization of the right MCA and ACA branches compared with the contralateral side (small arrows).

FIG 2.

Brain MR imaging of patient 2 performed on day 1. Axial T1-weighted image (A and B), T2-weighted (C and D) and diffusion-weighted (E–G) images show bilateral atrophy and abnormal T1 and T2 signal intensity of the thalami (arrowheads) and perirolandic regions (arrows) in the context of hypoxic-ischemic lesions. Also note multiple areas of acute ischemic infarct distributed in the right MCA territory and watershed region (open arrows). MRA (H) demonstrates reduced flow-related signal of the right MCA branches (small arrow).

FIG 3.

Longitudinal neuroimaging evaluation of patient 5. Initial brain MR imaging obtained at 18 days of life, including axial T1-weighted image (A), axial (B) and coronal (C) T2-weighted images, axial T2* image (D) and diffusion-weighted image (E), demonstrate a large ischemic infarct in the superficial and deep territory of the right MCA in the late subacute or early chronic phase (arrows). There are associated areas of cortical laminar necrosis (thin white arrow) and a focus of hemorrhagic transformation (thin black arrow). Also note signs of ipsilateral thalamic diaschisis (thick black arrow) and Wallerian degeneration of the corticospinal tract (arrowhead). Follow-up brain MR imaging performed at 6 months (F–J). Axial T1-weighted image (A) and axial (B) and coronal (C) T2-weighted images depict progressive cystic encephalomalacia and atrophy in the infarcted area with ex vacuo enlargement of the adjacent CSF spaces (asterisks). MRA reveals reduced visibility of right MCA branches (arrow). Axial directionally encoded color fractional anisotropy (FA) map at the level of the basal ganglia shows markedly reduced FA of the posterior limb of the right internal capsule (arrowhead).

FIG 4.

Schematic representation of the placental fetal vascularization and histologic features of fetal vascular malperfusion. 1. Vessel of umbilical cord. 2. Amniochorial vessels (A, A′, B, B′). 3. First-order stem vessels (C, C′). 4. Second-order stem vessels (D, D′). 5. Third-order stem vessels (E, E′, F). 6. Fourth-order stem vessels (F′, G, G′, H). A. Amniochorial vessel with dilated lumen occupied by a floating thrombus adhering to the wall by means of coagulation (patient 5). A′. Detail of the previous figure: evidence of wall damage in the form of a necrotic fibrinoid band (patient 5). B. Amniochorial vessel with dilated lumen in which a thrombus in various phases of evolution adheres to the wall; the thrombus has a fibrous nucleus, at the margins of which a recent coagulation and a fibrous thrombus in a medium stage of evolution are observed (patient 5). B′. Detail of B: granulocytic infiltrate of the wall indicating vasculitis as the cause of thrombosis (patient 5). C. First-order stem vessel totally occupied by a long-standing thrombus adherent to the wall (patient 1). C′. Detail of C, a segment of the destructured wall shows evolving lesions after adhesion of the thrombus (patient 1). D. Second-order stem vessel with a thrombotic formation occluding the lumen without adhering to the wall (patient 3). D′. Second-order stem vessel with wall lesion and initial detachment of a floating thrombus into the bloodstream. E. Third-order stem vessel displaying wall damage and initial adhesion of a fibrinoid thrombus. E′. Third-order stem vessel with the lumen completely occluded by a long-standing thrombotic formation hampering the recognition of vessel wall structure (patient 1). F. Third-order stem vessel with a long-standing partly recanalized occlusive thrombus (patient 1). F′. Fourth-order stem vessel: occluded lumen with revascularization; adjacent to this, a totally occluded vessel whose wall structure is no longer recognizable (patient 4). G. Fourth-order stem vessel displaying initial recanalization and endothelial proliferation promoting endoluminal neoangiogenesis (patient 1). G′. Detail of G showing the intermixing of nonagglutinated erythrocytes and incomplete neo-formed vessels (patient 1). H. Fourth-order stem vessel: the lumen is occupied by a long-standing thrombotic formation but displays recanalization; villi undergoing ischemic necrosis caused by perfusion block (patient 1). H′. Group of villi undergoing ischemic necrosis; long-standing lesion integrates the picture of so-called avascularized villi (patient 3).