NeoQuest March 2022: Abnormal Cranial Ultrasound Findings in a Newborn

A male infant was delivered at 34 weeks’ gestation via cesarean section following a failed induction of labor for pre-eclampsia. Prenatal labs and physical exam were unremarkable except for a head circumference in the 8th percentile. The infant was started on nasogastric feeds. At term postmenstrual age, he still had disorganized oromotor skills. A cranial ultrasound showed the findings in Figure 1A-B, and the infant was diagnosed with an infectious disease. What complication is most likely associated with this finding?

Figure 1A [left] Figure 1B [right]: Coronal and parasagittal views of the infant’s cranial ultrasound demonstrating hyperechogenic linear streaks within the thalami and basal ganglia (white arrows). From: Almeida AC, Freitas A, Vieira MJ. A newborn with an incidental finding on cranial ultrasound. Neoreviews. 2022;23(3):e221–e224.

A. Aplastic anemia
B. Cataracts
C. Cerebral palsy
D. Sensorineural hearing loss

Answer: D. Sensorineural hearing loss

Explanation
The cranial ultrasound obtained for protracted poor oral feeding in this infant demonstrates an incidental finding of increased echogenic streaks in the lenticulostriate arteries within the basal ganglia and thalamus. This finding is consistent with lenticulostriate vasculopathy (LSV).¹ Although LSV can represent a nonspecific finding, the most commonly associated infectious etiology is cytomegalovirus (CMV) infection, which was the ultimate diagnosis in this infant’s case.²

CMV is a type of herpesvirus that can cause a congenital viral infection. More than 60% of the population in the United States are seropositive for CMV, with an even higher prevalence of 90% in less developed countries.³ The most common route of transmission is via primary maternal infection during pregnancy; however, postnatal transmission can also occur, particularly through unpasteurized breast milk.³ Although the majority of infants are asymptomatic, clinical manifestations in symptomatic infants can include hepatosplenomegaly with liver failure and conjugated hyperbilirubinemia, a classic “blueberry muffin rash” with thrombocytopenia, microcephaly, and chorioretinitis.³ Most importantly, congenital CMV infection is the most common cause of nonhereditary sensorineural hearing loss (Option D). Treatment with valganciclovir in infants with symptomatic congenital CMV infection has been shown to reduce hearing loss and improve neurologic outcomes in randomized controlled trials.^4–6

Neuroimaging findings for infants affected by congenital CMV range from periventricular calcifications (Figure 2) to cortical dysplasia, ventriculomegaly, lissencephaly, and LSV, as seen in this clinical vignette.³  LSV is an ultrasound finding characterized by hyperechogenic lines within the deep gray matter located within the lenticulostriated branches of the middle cerebral artery, which are found in the thalamus and the basal ganglia (Figure 1A–B).^1,7 Although the pathogenesis of LSV is unclear, doppler blood flow studies have demonstrated arterial signals within these echogenic “candlestick-like strips”, suggesting the presence of a vascular lesion that has been commonly associated with congenital TORCH infections including CMV.^7–8 When present, clinicians should consider screening for congenital CMV infection and review prenatal labs with particular attention to rubella, HIV, and syphilis screening tests.⁸

Figure 2: A. Coronal view of a cranial ultrasound with periventricular calcifications (arrow) adjacent to the left lateral ventricle. B. Axial view of a computed tomography scan demonstrating periventricular calcifications (arrows) and ventriculomegaly in an infant with congenital CMV infection. From: Tian C, Ali SA, Weitkamp J. Congenital infections, part 1: Cytomegalovirus, Toxoplasma, Rubella and Herpes simplex. Neoreviews. 2010;11(8):e436-446

Aplastic anemia (Option A) is a complication of an acute parvovirus B19 infection. Infection can occur via transmission of respiratory droplets, hematogenous spread, and vertical transmission, with the highest risk occurring during the first and second trimesters.⁹ Clinical manifestations range from nonimmune hydrops to congestive heart failure secondary to profound aplastic anemia and myocarditis, while severe infection can lead to fetal demise in up to 10% of affected women.^10–11 Although rare, parvovirus infection can lead to a disturbance of cerebral neuronal migration characterized by polymicrogyria, a malformation of cortical development known to occur during the second trimester (Figure 3).¹⁰ However, it is not associated with LSV. Our infant did not have clinical symptoms or known risk factors for parvovirus infection, and his cranial ultrasound findings did not demonstrate a neuronal migration disorder.  

Figure 3: A. Axial, and B. Coronal views of a brain MRI in a term infant with congenital parvovirus B19 infection demonstrating extensive polymicrogyria (white arrow). From: Satti KF, Ali SA, Weitkamp JH. Congenital infections, part 2: parvovirus, listeria, tuberculosis, syphilis, and varicella. Neoreviews. 2010;11(12):e681–695

Cataracts (Option B), along with deafness and a patent ductus arteriosus, comprise the classic clinical triad caused by congenital rubella syndrome.³ This rare condition is transmitted vertically with fewer than 10 cases per year in the United States since the measles-mumps-rubella vaccine was introduced.³ Central nervous system involvement can result in microcephaly or meningoencephalitis with cranial ultrasound findings of ventriculomegaly, subependymal cysts, or periventricular calcifications.¹¹ LSV is not found in patients with a rubella infection. The infant in this vignette was born to a mother who was rubella immune with an otherwise normal physical exam.

Cerebral palsy (Option C) is the most common motor disorder among children, particularly in those born preterm or with low birthweight, and is typically diagnosed by two years of age. It is characterized by nonprogressive disorders of movement and posture.¹² This condition can have multiple inciting factors ranging from infection to perinatal insult, with perinatal arterial ischemic stroke (PAIS) representing the leading cause of hemiparetic cerebral palsy.¹³ PAIS occurs between 20 weeks’ gestation and 28 days of postnatal age and is caused by a vascular occlusion most commonly involving the left middle cerebral artery territory.¹³ Because cranial ultrasound may miss an infarction in the deep gray matter structures, MRI with diffusion-weighted imaging is recommended to diagnose a stroke and delineate the vascular territory affected (Figure 4).¹⁴ Our infant did not present with neurologic symptoms suggestive of a stroke and had evidence of LSV on an ultrasound, which has not been associated with PAIS.

Figure 4: Axial view from diffusion weighted imaging on a brain MRI demonstrating ischemic stroke in the left middle cerebral artery territory (white arrow). From: Srivastava R, Kirton A. Perinatal stroke: a practical approach to diagnosis and management. Neoreviews. 2021;22(3):e163–176

Did you know?

• Congenital infections (eg, CMV) and hypoxic-ischemic injury are the most common conditions associated with LSV; however, LSV can also represent a transient finding in healthy preterm infants.⁸

What percentage of infants ultimately diagnosed with a perinatal stroke are asymptomatic at birth?

To find the answer, please refer to the following article: Srivastava R, Kirton A. Perinatal stroke: a practical approach to diagnosis and management. Neoreviews. 2021;22(3):e163–176

NeoQuest March Authors
Faith Kim, Columbia University Medical Center, NY, NY
Anisha Bhatia, Perinatal and Pediatric Services, Inc. Canton, Ohio

References

1. Almeida AC, Freitas A, Vieira MJ. A newborn with an incidental finding on cranial ultrasound. Neoreviews. 2022;23(3):e221–e224
2. Amir J, Schwarz M, Levy I, Haimi-Cohen Y, Pardo J. Is lenticulostriated vasculopathy a sign of central nervous system insult in infants with congenital CMV infection? Arch Dis Child. 2011;96(9):846–850
3. Tian C, Ali SA, Weitkamp JH. Congenital infections, part 1: cytomegalovirus, toxoplasma, rubella, and herpes simplex. Neoreviews. 2010;11(8):e436–446
4. Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, Jacobs RF, Vaudry W, Pass RF, Kiell JM, Soong S, Whitley R, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003;143(1):16–25
5. Kimberlin DW, Jester PM, Sanchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372(10):933–943
6. Acosta E, Bowlin T, Brooks J, et al. Advances in the development of therapeutics for cytomegalovirus infections. J Infect Dis. 2020;221(Suppl 1):S32–S44
7. Sisman J, Chalak L, Heyne R, Pritchard M, Weakley D, Brown LS, Rosenfeld CR. Lenticulostriate vasculopathy in preterm infants: new classification, clinical associations and neurodevelopmental outcome. J Perinatol. 2018;38(10):1370–1378
8. Cantey JB, Sisman J. The etiology of lenticulostriate vasculopathy and the role of congenital infections. Early Hum Dev. 2015;91(7):427–430
9. Satti KF, Ali SA, Weitkamp JH. Congenital infections, part 2: parvovirus, listeria, tuberculosis, syphilis, and varicella. Neoreviews. 2010;11(12):e681–695
10. Schulert GS, Walsh WF, Weitkamp JH. Polymicrogyria and congenital parvovirus B19 infection. AJP Rep. 2011;1(2):105–110
11. Boucoiran I, Kakkar F, Renaud C. Maternal infections. Handb Clin Neurol. 2020;173:401–422
12. Herskind A, Greisen G, Nielsen JB. Early identification and intervention to cerebral palsy. Dev Med Child Neurol. 2015;57(1):29–36
13. Roach GD. Perinatal arterial ischemic stroke. Neoreviews. 2020;21(11):e741–748
14. Srivastava R, Kirton A. Perinatal stroke: a practical approach to diagnosis and management. Neoreviews. 2021;22(3):e163–176