Unusual presentation of fetal ventriculomegaly: a case report
Article information
Abstract
Fetal ventriculomegaly (VM) is a relatively common finding during prenatal examinations and occurs in approximately 0.2% of live births. Although there are various causes, obstructive VM due to cerebellar hemorrhage is exceedingly rare. A 33-year-old primigravida presented at 32 weeks of gestation with VM. At 36 weeks of age, a male infant was delivered via cesarean section. Postnatal imaging revealed severe bilateral hydrocephalus and space-occupying lesions in the cerebellum. Initial concerns about a potential germ cell tumor were raised due to elevated alpha-fetoprotein levels in both serum and cerebrospinal fluid. An external ventricular drain was placed to manage obstructive hydrocephalus. When the baby was 1 month old, surgical exploration revealed an old blood clot without any evidence of a tumor. Histopathological examination confirmed an old hemorrhage with no malignant cells. This case underscores the diagnostic challenges in distinguishing between hemorrhages and tumors in the context of fetal VM. Despite elevated alpha-fetoprotein levels, no tumors were identified. The underlying cause of cerebellar hemorrhage remains unclear despite extensive workups. Nevertheless, this case report details multifaceted diagnostic efforts to address the rare occurrence of cerebellar hemorrhage related to fetal VM, leading to a comprehensive case presentation.
INTRODUCTION
Fetal ventriculomegaly (VM) is often detected during prenatal examinations and occurs in approximately two out of every 1,000 live births [1]. Potential causes of fetal VM include developmental abnormalities, congenital infections, cerebral hypoxia or infarction, intraventricular hemorrhage, and obstructions [2].
Obstructive fetal VM due to the mass effect of cerebellar hemorrhage is extremely rare [3]. The major risk factors include premature birth and low birth weight. Although the exact incidence is unknown, it occurs in approximately 3% of infants weighing less than 1,500 g and 9% of infants weighing less than 750 g. If microbleeding is included in the definition of cerebellar hemorrhage, its incidence can reach 20% [4].
This case report discusses the diagnostic process and management of an infant with obstructive fetal VM caused by cerebellar hemorrhage.
CASE REPORT
A 33-year-old primigravida presented to the emergency department at 32 weeks 5 days of gestation with fever and labor pain. The patient was under surveillance for fetal VM at another hospital (Fig. 1A). Upon admission, she did not exhibit regular labor pain but complained of persistent abdominal discomfort. Conservative management was provided, and her symptoms improved, leading to discharge. During follow-up at the outpatient clinic, the fetal VM persisted on ultrasonography without worsening (Fig. 1B). The patient had no pregnancy-induced hypertension, bleeding tendency, or TORCH infection and no medications were administered.
At 36 weeks and 4 days of gestation, the mother underwent cesarean section and delivered a boy weighing 3,050 g (67th percentile) with Apgar scores of 8 and 8 at 1 and 5 minutes, respectively, and an umbilical cord pH of 7.373. Physical examination of the infant after birth revealed no bulging of the anterior fontanelle or other significant findings. Initial brain ultrasonography revealed severe bilateral hydrocephalus suggestive of obstructive hydrocephalus.
To investigate the possibility of a tumor or tumor bleeding causing the space-occupying lesion, serum levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (β-hCG) were measured. The serum AFP level measured 1 week after birth was 117,621 ng/mL (preterm neonate reference range, 333-13,992) [5], and the β-hCG level was 1.8 mIU/mL (reference range, <10) [5]. There was no bleeding tendency, and TORCH infection was not identified.
Brain magnetic resonance imaging (MRI) revealed a space-occupying lesion in the cerebellum (Fig. 2A, B). The primary differential diagnosis included an unusual location for the hemorrhage, followed by a neoplasm and, least likely, a thrombosed vein of Galen malformation.
The neurosurgeons placed an external ventricular drain (EVD) to decompress the obstructive hydrocephalus. AFP and β-hCG levels were measured in the cerebral spinal fluid (CSF), showing an elevated CSF AFP level of 1,459 ng/mL (reference range, 0.0-10.0) [6] and a normal CSF β-hCG level of 1.7 mIU/mL (reference range, <50) [7]. Based on the results of the serum and CSF tests, considering the elevated AFP and normal β-hCG levels, a germ cell tumor could not be completely ruled out.
Before the surgical resection of the cerebellar lesion, an anomaly workup was performed, including spine MRI and echocardiography. Spinal magnetic resonance imaging showed no abnormalities, and echocardiography revealed a small atrial septal defect measuring 2.5 mm in diameter. Testicular ultrasonography ruled out testicular germ cell tumors.
Periodic brain ultrasonography confirmed that the hydrocephalus had not worsened. Serial serum and CSF AFP and β-hCG levels gradually decreased in AFP levels over time.
At 1 month of age, the infant underwent surgical removal of the cerebellar mass. Intraoperatively, no tumorous tissue was identified. Instead, the lesion was mainly composed of an old blood clot. A frozen biopsy confirmed the absence of a tumor, and the final histopathology revealed no definite malignant cells, consistent with an old hemorrhage.
Postoperative brain MRI showed no signs of worsening of VM (Fig. 2C), and outpatient imaging surveillance was planned as long as the patient’s condition remained stable after discharge. Elevated serum and CSF AFP levels suggested the presence of an extracranial germ cell tumor, which was ruled out by chest and abdominal computed tomography.
Genetic testing, including chromosomal analysis and microdeletion and duplication studies, has yielded unremarkable results when investigating the potential underlying causes of fetal cerebellar hemorrhage.
The infant was discharged and continued to be monitored in the outpatient clinic with plans for long-term monitoring.
This case report was exempted from review by the Institutional Review Board (IRB) of Kyungpook National University Hospital, with a waiver for informed consent (IRB No. KNUCH 2024-03-016).
DISCUSSION
Fetal VM is a relatively common finding during pregnancy, with a reported incidence of 0.3-1.0 per 1,000 births [1]. Various underlying causes exist, including developmental abnormalities, brain parenchymal injury from congenital infections, atrophy, and hemorrhage, such as intraventricular hemorrhage, which can also lead to VM [8].
After birth, imaging studies, such as brain ultrasonography and MRI, are essential, and tumor markers, such as serum and CSF AFP and β-hCG, should be checked to consider the possibility of tumor-related bleeding. In this infant, the elevated AFP level with a normal β-hCG suggested the presence of a germ cell tumor.
Despite elevated serum and CSF AFP levels, no tumors were identified on tissue sampling. Although the possibility of an extracranial tumor source was explored using imaging studies, no tumor origin was detected. Another possibility is that AFP levels can be elevated in premature infants; however, interpreting its significance can be challenging due to the lack of well-defined reference ranges in this population.
Ideally, the causative lesion should be removed to treat obstructive hydrocephalus. In neonates, where surgical access may be difficult, a temporary EVD can be placed while monitoring weight gain; however, EVD placement is not a definitive treatment and carries infection risks, making its long-term use inadvisable. Ultimately, surgical resection, followed by tissue diagnosis, is necessary to establish the precise cause. If tumor-related bleeding is identified, adjuvant chemotherapy or radiation therapy may be considered (depending on the patient’s age) [7].
Cerebellar hemorrhage in neonates may be related to pregnancy-induced hypertension, coagulopathy, infection, or medication. However, in this patient, none of these issues were observed in the mother. Therefore, we considered various other possibilities for identifying the cause of the cerebellar hemorrhage. Despite extensive investigations, the underlying cause of hemorrhage in this patient remains elusive. To further explore the potential genetic causes, whole-genome sequencing could be considered in addition to microarray analyses. Genetic disorders that can cause cerebellar hemorrhage include hemostatic gene disorders (factor V deficiency, von Willebrand disease, and factor VII deficiency), prothrombotic genes (factor V Leiden, MTHFR mutation, and protein C deficiency), and X-linked GATA1 gene mutations [7].
Given the cerebellar volume loss due to hemorrhage and cerebral volume loss due to hydrocephalus, neurological sequelae are expected. In patients with cerebellar hemorrhage, the median survival times were 5 years and 6 months after survival and discharge, respectively. Additionally, recurrent intracerebral hemorrhage, and ischemic stroke, specifically after cerebellar intracranial hemorrhage, may occur in the future [9]. Regular long-term developmental assessments are crucial for achieving optimal neurological outcomes. Continuous monitoring of hydrocephalus progression using imaging is necessary for timely intervention. In addition, aggressive rehabilitative therapy should be pursued to minimize developmental delays. Although the diagnosis was not confirmed, this case was reported due to the rare occurrence of fetal VM due to cerebellar hemorrhage.