Fetal stroke and cerebrovascular disease: Advances in understanding from lenticulostriate and venous imaging, alloimmune thrombocytopaenia and monochorionic twins

Abstract

Fetal stroke is an important cause of cerebral palsy but is difficult to diagnose unless imaging is undertaken in pregnancies at risk because of known maternal or fetal disorders. Fetal ultrasound or magnetic resonance imaging may show haemorrhage or ischaemic lesions including multicystic encephalomalacia and focal porencephaly. Serial imaging has shown the development of malformations including schizencephaly and polymicrogyra after ischaemic and haemorrhagic stroke. Recognised causes of haemorrhagic fetal stroke include alloimmune and autoimmune thrombocytopaenia, maternal and fetal clotting disorders and trauma but these are relatively rare. It is likely that a significant proportion of periventricular and intraventricular haemorrhages are of venous origin. Recent evidence highlights the importance of arterial endothelial dysfunction, rather than thrombocytopaenia, in the intraparenchymal haemorrhage of alloimmune thrombocytopaenia. In the context of placental anastomoses, monochorionic diamniotic twins are at risk of twin twin transfusion syndrome (TTTS), or partial forms including Twin Oligohydramnios Polyhydramnios Sequence (TOPS), differences in estimated weight (selective Intrauterine growth Retardation; sIUGR), or in fetal haemoglobin (Twin Anaemia Polycythaemia Sequence; TAPS). There is a very wide range of ischaemic and haemorrhagic injury in a focal as well as a global distribution. Acute twin twin transfusion may account for intraventricular haemorrhage in recipients and periventricular leukomalacia in donors but there are additional risk factors for focal embolism and cerebrovascular disease. The recipient has circulatory overload, with effects on systemic and pulmonary circulations which probably lead to systemic and pulmonary hypertension and even right ventricular outflow tract obstruction as well as the polycythaemia which is a risk factor for thrombosis and vasculopathy. The donor is hypovolaemic and has a reticulocytosis in response to the anaemia while maternal hypertension and diabetes may influence stroke risk. Understanding of the mechanisms, including the role of vasculopathy, in well studied conditions such as alloimmune thrombocytopaenia and monochorionic diamniotic twinning may lead to reduction of the burden of antenatally sustained cerebral palsy.

Keywords: Anemia; COL4A1; COL4A2; Cytomegalovirus; Dural venous ectasia with thrombosis; Embolus; Encephalomalcia; Endothelial dysfunction; FNAIT; Factor V leiden; Fetal and neonatal alloimmune thrombocytopenia; Fetal periventricular venous infarction; Fetus; Focal cortical dysplasia; Focal ischemia; Hydrancephaly; Hypovolemia; Intraparenchymal hemorrhage; Intraventricular hemorrhage; Lenticulostriate vasculopathy; Maternal cocaine; Maternal warfarin; Middle cerebral artery peak systolic velocity; Monochorionic diamniotic twins; Parabiotic; Parvovirus B19; Periventricular hemorrhage; Periventricular leukomalacia; Placental anastomoses; Polycythemia; Polymicrogyria; Porencephaly; Posterior fossa hemorrhage; Prothrombotic; Pulmonary hypertension; Right ventricular outflow tract obstruction; Schizencephaly; Selective intrauterine growth retardation; Stroke; Subarachnoid hemorrhage; TAPS; TOPS; TRAP; TTTS; Thermolabile methylene tetrahydrofolate reductase polymorphism; Trauma; Twin anemia polycythemia syndrome; Twin oligohydramnios polyhydramnios syndrome; Twin reverse arterial perfusion; Twin twin transfusion syndrome; Vascular disruption; Vein of Galen malformation; Venous sinus thrombosis; Zika; sIUGR.