Neuroimaging of Fetal Infection

Ashley J. Robinson; M. Ashraf Ederies

doi:10.1055/s-0037-1604219

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2017; 15(05): 192-200
DOI: 10.1055/s-0037-1604219

Review Article

Georg Thieme Verlag KG Stuttgart · New York

Neuroimaging of Fetal Infection

Ashley J. Robinson

¹Department of Diagnostic Imaging, Sidra Medical and Research Center, Doha, Qatar

²Department of Clinical Radiology, Weill Cornell Medical College, New York, New York, United States

,

M. Ashraf Ederies

¹Department of Diagnostic Imaging, Sidra Medical and Research Center, Doha, Qatar

²Department of Clinical Radiology, Weill Cornell Medical College, New York, New York, United States

› Author Affiliations

Abstract

Infection during pregnancy is common and the developing fetal brain is vulnerable to vertical transmission due to immaturity of the fetal immune system. Infection is a major cause of multiple organ abnormalities, including the neuraxis, due to the neurotropism of the infectious agents. This review sets out to give an overview of fetal infection, review the general principles of the nature and timing of the infectious insult with respect to outcomes, review the neuroimaging of infection by ultrasound and magnetic resonance imaging (MRI), and review the various pathogens involved, including the two most common, cytomegalovirus (CMV) and Toxoplasma, and also other common viral and nonviral infections.

Keywords

Toxoplasma - cytomegalovirus - sensorineural hearing loss - human herpes virus - herpes simplex virus - fetal MRI - congenital zika virus - pseudo-TORCH

Full Text

References

References
1 Bailão LA, Osborne NG, Rizzi MC, Bonilla-Musoles F, Duarte G, Bailão TC. Ultrasound markers of fetal infection part 1: viral infections. Ultrasound Q 2005; 21 (04) 295-308
2 Crino JP. Ultrasound and fetal diagnosis of perinatal infection. Clin Obstet Gynecol 1999; 42 (01) 71-80 ; quiz 174–175
3 Bale Jr JF. Fetal infections and brain development. Clin Perinatol 2009; 36 (03) 639-653
4 Girard N, Gire C, Sigaudy S. , et al. MR imaging of acquired fetal brain disorders. Childs Nerv Syst 2003; 19 (7–8): 490-500
5 Barkovich AJ, Lindan CE. Congenital cytomegalovirus infection of the brain: imaging analysis and embryologic considerations. Am J Neuroradiol 1994; 15 (04) 703-715
6 Carletti A, Colleoni GG, Perolo A. , et al. Prenatal diagnosis of cerebral lesions acquired in utero and with a late appearance. Prenat Diagn 2009; 29 (04) 389-395
7 Bailão LA, Osborne NG, Rizzi MC, Bonilla-Musoles F, Duarte G, Bailão TC. Ultrasound markers of fetal infection, part 2: bacterial, parasitic, and fungal infections. Ultrasound Q 2006; 22 (02) 137-151
8 Steinlin MI, Nadal D, Eich GF, Martin E, Boltshauser EJ. Late intrauterine cytomegalovirus infection: clinical and neuroimaging findings. Pediatr Neurol 1996; 15 (03) 249-253
9 Beke A, Latkóczy K, Nagy GR. , et al. Comparison of prevalence of Toxoplasma and cytomegalovirus infection in cases with fetal ultrasound markers in the second trimester of pregnancy. Prenat Diagn 2011; 31 (10) 945-948
10 Barkovich AJ, Girard N. Fetal brain infections. Childs Nerv Syst 2003; 19 (7–8): 501-507
11 Garcia-Flores J, Recio M, Uriel M. , et al. Fetal magnetic resonance imaging and neurosonography in congenital neurological anomalies: supplementary diagnostic and postnatal prognostic value. J Matern Fetal Neonatal Med 2013; 26 (15) 1517-1523
12 Gay-Andrieu F, Marty P, Pialat J, Sournies G, Drier de Laforte T, Peyron F. Fetal toxoplasmosis and negative amniocentesis: necessity of an ultrasound follow-up. Prenat Diagn 2003; 23 (07) 558-560
13 Doneda C, Parazzini C, Righini A. , et al. Early cerebral lesions in cytomegalovirus infection: prenatal MR imaging. Radiology 2010; 255 (02) 613-621
14 Lipitz S, Hoffmann C, Feldman B, Tepperberg-Dikawa M, Schiff E, Weisz B. Value of prenatal ultrasound and magnetic resonance imaging in assessment of congenital primary cytomegalovirus infection. Ultrasound Obstet Gynecol 2010; 36 (06) 709-717
15 Soussotte C, Maugey-Laulom B, Carles D, Diard F. Contribution of transvaginal ultrasonography and fetal cerebral MRI in a case of congenital cytomegalovirus infection. Fetal Diagn Ther 2000; 15 (04) 219-223
16 de Vries LS, Gunardi H, Barth PG, Bok LA, Verboon-Maciolek MA, Groenendaal F. The spectrum of cranial ultrasound and magnetic resonance imaging abnormalities in congenital cytomegalovirus infection. Neuropediatrics 2004; 35 (02) 113-119
17 Salmaso R, Franco R, de Santis M. , et al. Early detection by magnetic resonance imaging of fetal cerebral damage in a fetus with hydrops and cytomegalovirus infection. J Matern Fetal Neonatal Med 2007; 20 (07) 559-561
18 Picone O, Simon I, Benachi A, Brunelle F, Sonigo P. Comparison between ultrasound and magnetic resonance imaging in assessment of fetal cytomegalovirus infection. Prenat Diagn 2008; 28 (08) 753-758
19 Cannie MM, Devlieger R, Leyder M. , et al. Congenital cytomegalovirus infection: contribution and best timing of prenatal MR imaging. Eur Radiol 2016; 26 (10) 3760-3769
20 Oosterom N, Nijman J, Gunkel J. , et al. Neuro-imaging findings in infants with congenital cytomegalovirus infection: relation to trimester of infection. Neonatology 2015; 107 (04) 289-296
21 Averill LW, Kandula VV, Akyol Y, Epelman M. Fetal brain magnetic resonance imaging findings in congenital cytomegalovirus infection with postnatal imaging correlation. Semin Ultrasound CT MR 2015; 36 (06) 476-486
22 O'Rourke D, Bradley L, King MD, Ryan S. Leukoencephalopathy with anterior temporal cysts due to congenital CMV infection diagnosed retrospectively. J Neuroimaging 2010; 20 (03) 292-293
23 Massoud M, Cagneaux M, Garel C. , et al. Prenatal unilateral cerebellar hypoplasia in a series of 26 cases: significance and implications for prenatal diagnosis. Ultrasound Obstet Gynecol 2014; 44 (04) 447-454
24 Guibaud L, Attia-Sobol J, Buenerd A. , et al. Focal sonographic periventricular pattern associated with mild ventriculomegaly in foetal cytomegalic infection revealing cytomegalic encephalitis in the third trimester of pregnancy. Prenat Diagn 2004; 24 (09) 727-732
25 Jayaram PM, Wake CR. A rare case of absent corpus callosum with severe ventriculomegaly due to congenital herpes simplex infection. J Obstet Gynaecol 2010; 30 (03) 316
26 Meyberg-Solomayer GC, Fehm T, Muller-Hansen I. , et al. Prenatal ultrasound diagnosis, follow-up, and outcome of congenital varicella syndrome. Fetal Diagn Ther 2006; 21 (03) 296-301
27 Auriti C, Piersigilli F, De Gasperis MR, Seganti G. Congenital varicella syndrome: still a problem?. Fetal Diagn Ther 2009; 25 (02) 224-229
28 Ong CL, Daniel ML. Antenatal diagnosis of a porencephalic cyst in congenital varicella-zoster virus infection. Pediatr Radiol 1998; 28 (02) 94
29 Deasy NP, Jarosz JM, Cox TC, Hughes E. Congenital varicella syndrome: cranial MRI in a long-term survivor. Neuroradiology 1999; 41 (03) 205-207
30 Dimova PS, Karparov AA. Congenital varicella syndrome: case with isolated brain damage. J Child Neurol 2001; 16 (08) 595-597
31 Stagno S, Pass RF, Cloud G. , et al. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA 1986; 256 (14) 1904-1908
32 Demmler GJ. Infectious Diseases Society of America and Centers for Disease Control. Summary of a workshop on surveillance for congenital cytomegalovirus disease. Rev Infect Dis 1991; 13 (02) 315-329
33 Malm G, Engman ML. Congenital cytomegalovirus infections. Semin Fetal Neonatal Med 2007; 12 (03) 154-159
34 Freij BJ, Sever JL. Herpesvirus infections in pregnancy: risks to embryo, fetus, and neonate. Clin Perinatol 1988; 15 (02) 203-231
35 Suzuki Y, Toribe Y, Mogami Y, Yanagihara K, Nishikawa M. Epilepsy in patients with congenital cytomegalovirus infection. Brain Dev 2008; 30 (06) 420-424
36 Watt-Morse ML, Laifer SA, Hill LM. The natural history of fetal cytomegalovirus infection as assessed by serial ultrasound and fetal blood sampling: a case report. Prenat Diagn 1995; 15 (06) 567-570
37 Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med 1992; 326 (10) 663-667
38 Malm G, Gröndahl EH, Lewensohn-Fuchs I. Congenital cytomegalovirus infection: a retrospective diagnosis in a child with pachygyria. Pediatr Neurol 2000; 22 (05) 407-408
39 Lipitz S, Yinon Y, Malinger G. , et al. Risk of cytomegalovirus-associated sequelae in relation to time of infection and findings on prenatal imaging. Ultrasound Obstet Gynecol 2013; 41 (05) 508-514
40 Amir J, Atias J, Linder N, Pardo J. Follow-up of infants with congenital cytomegalovirus and normal fetal imaging. Arch Dis Child Fetal Neonatal Ed 2016; 101 (05) F428-F432
41 Mehta NM, Hartnoll G. Congenital CMV with callosal lipoma and agenesis. Pediatr Neurol 2001; 24 (03) 222-224
42 Malinger G, Lev D, Zahalka N. , et al. Fetal cytomegalovirus infection of the brain: the spectrum of sonographic findings. Am J Neuroradiol 2003; 24 (01) 28-32
43 Leyder M, Vorsselmans A, Done E. , et al. Primary maternal cytomegalovirus infections: accuracy of fetal ultrasound for predicting sequelae in offspring. Am J Obstet Gynecol 2016; 215 (05) 638.e1-638.e8
44 Dogan Y, Yuksel A, Kalelioglu IH, Has R, Tatli B, Yildirim A. Intracranial ultrasound abnormalities and fetal cytomegalovirus infection: report of 8 cases and review of the literature. Fetal Diagn Ther 2011; 30 (02) 141-149
45 Picone O, Teissier N, Cordier AG. , et al. Detailed in utero ultrasound description of 30 cases of congenital cytomegalovirus infection. Prenat Diagn 2014; 34 (06) 518-524
46 Tomà P, Magnano GM, Mezzano P, Lazzini F, Bonacci W, Serra G. Cerebral ultrasound images in prenatal cytomegalovirus infection. Neuroradiology 1989; 31 (03) 278-279
47 White AL, Hedlund GL, Bale Jr JF. Congenital cytomegalovirus infection and brain clefting. Pediatr Neurol 2014; 50 (03) 218-223
48 Benoist G, Salomon LJ, Mohlo M, Suarez B, Jacquemard F, Ville Y. Cytomegalovirus-related fetal brain lesions: comparison between targeted ultrasound examination and magnetic resonance imaging. Ultrasound Obstet Gynecol 2008; 32 (07) 900-905
49 Ramenghi LA, Domizio S, Quartulli L, Sabatino G. Prenatal pseudocysts of the germinal matrix in preterm infants. J Clin Ultrasound 1997; 25 (04) 169-173
50 Twickler DM, Perlman J, Maberry MC. Congenital cytomegalovirus infection presenting as cerebral ventriculomegaly on antenatal sonography. Am J Perinatol 1993; 10 (05) 404-406
51 Simonazzi G, Guerra B, Bonasoni P. , et al. Fetal cerebral periventricular halo at midgestation: an ultrasound finding suggestive of fetal cytomegalovirus infection. Am J Obstet Gynecol 2010; 202 (06) 599.e1-599.e5
52 Pugash D, Hendson G, Dunham CP, Dewar K, Money DM, Prayer D. Sonographic assessment of normal and abnormal patterns of fetal cerebral lamination. Ultrasound Obstet Gynecol 2012; 40 (06) 642-651
53 Malinger G, Lev D, Ben Sira L, Kidron D, Tamarkin M, Lerman-Sagie T. Congenital periventricular pseudocysts: prenatal sonographic appearance and clinical implications. Ultrasound Obstet Gynecol 2002; 20 (05) 447-451
54 Malinger G, Lev D, Lerman-Sagie T. Imaging of fetal cytomegalovirus infection. Fetal Diagn Ther 2011; 29 (02) 117-126
55 Inaba Y, Motobayashi M, Nishioka M. , et al. Correlation between white matter lesions and intelligence quotient in patients with congenital cytomegalovirus infection. Pediatr Neurol 2016; 55: 52-57
56 Farkas N, Hoffmann C, Ben-Sira L. , et al. Does normal fetal brain ultrasound predict normal neurodevelopmental outcome in congenital cytomegalovirus infection?. Prenat Diagn 2011; 31 (04) 360-366
57 Parisot S, Droulle P, Feldmann M, Pinaud P, Marchal C. Unusual encephaloclastic lesions with paraventricular calcification in congenital rubella. Pediatr Radiol 1991; 21 (03) 229-230
58 Cluver C, Meyer R, Odendaal H, Geerts L. Congenital rubella with agenesis of the inferior cerebellar vermis and total anomalous pulmonary venous drainage. Ultrasound Obstet Gynecol 2013; 42 (02) 235-237
59 Yamashita Y, Matsuishi T, Murakami Y. , et al. Neuroimaging findings (ultrasonography, CT, MRI) in 3 infants with congenital rubella syndrome. Pediatr Radiol 1991; 21 (08) 547-549
60 Severino M, Zerem A, Biancheri R, Cristina E, Rossi A. Spontaneously regressing leukoencephalopathy with bilateral temporal cysts in congenital rubella infection. Pediatr Infect Dis J 2014; 33 (04) 422-424
61 Driggers RW, Ho CY, Korhonen EM. , et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 2016; 374 (22) 2142-2151
62 França GV, Schuler-Faccini L, Oliveira WK. , et al. Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation. Lancet 2016; 388 (10047): 891-897
63 Joob B, Wiwanitkit V. Fetal magnetic resonance imaging of fetus with Zika virus infection. Pediatr Neurol 2017; 68: e1
64 Vouga M, Baud D. Imaging of congenital Zika virus infection: the route to identification of prognostic factors. Prenat Diagn 2016; 36 (09) 799-811
65 Besnard M, Eyrolle-Guignot D, Guillemette-Artur P. , et al. Congenital cerebral malformations and dysfunction in fetuses and newborns following the 2013 to 2014 Zika virus epidemic in French Polynesia. Euro Surveill 2016; 21 (13)
66 Guillemette-Artur P, Besnard M, Eyrolle-Guignot D, Jouannic JM, Garel C. Prenatal brain MRI of fetuses with Zika virus infection. Pediatr Radiol 2016; 46 (07) 1032-1039
67 Soares de Oliveira-Szejnfeld P, Levine D, Melo AS. , et al. Congenital brain abnormalities and Zika virus: what the radiologist can expect to see prenatally and postnatally. Radiology 2016; 281 (01) 203-218
68 Melo AS, Aguiar RS, Amorim MM. , et al. Congenital Zika virus infection: beyond neonatal microcephaly. JAMA Neurol 2016; 73 (12) 1407-1416
69 Sanín-Blair JE, Gutiérrez-Márquez C, Herrera DA, Vossough A. Fetal magnetic resonance imaging findings in prenatal Zika virus infection. Fetal Diagn Ther 2017
70 Vorona GA, Lanni SM. Fetal magnetic resonance imaging evaluation of a 21-week fetus with Zika virus infection. Pediatr Neurol 2016; 65: 98-99
71 Araujo Júnior E, Carvalho FH, Tonni G, Werner H. Prenatal imaging findings in fetal Zika virus infection. Curr Opin Obstet Gynecol 2017; 29 (02) 95-105
72 Courtier J, Schauer GM, Parer JT, Regenstein AC, Callen PW, Glenn OA. Polymicrogyria in a fetus with human parvovirus B19 infection: a case with radiologic-pathologic correlation. Ultrasound Obstet Gynecol 2012; 40 (05) 604-606
73 Pistorius LR, Smal J, de Haan TR. , et al. Disturbance of cerebral neuronal migration following congenital parvovirus B19 infection. Fetal Diagn Ther 2008; 24 (04) 491-494
74 Sanapo L, Wien M, Whitehead MT. , et al. Fetal anemia, cerebellar hemorrhage and hypoplasia associated with congenital Parvovirus infection. J Matern Fetal Neonatal Med 2017; 30 (16) 1887-1890
75 Bonthius DJ, Wright R, Tseng B. , et al. Congenital lymphocytic choriomeningitis virus infection: spectrum of disease. Ann Neurol 2007; 62 (04) 347-355
76 Anderson JL, Levy PT, Leonard KB, Smyser CD, Tychsen L, Cole FS. Congenital lymphocytic choriomeningitis virus: when to consider the diagnosis. J Child Neurol 2014; 29 (06) 837-842
77 Reitter A, Stücker AU, Buxmann H. , et al. Prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection: a retrospective study. Infect Dis Obstet Gynecol 2013; 2013: 208482
78 Marquis JR, Bardeguez AD. Imaging of HIV infection in the prenatal and postnatal period. Clin Perinatol 1994; 21 (01) 125-147
79 Rac MW, Bryant SN, McIntire DD. , et al. Progression of ultrasound findings of fetal syphilis after maternal treatment. Am J Obstet Gynecol 2014; 211 (04) 426.e1-426.e6
80 al Shahwan S, Rossi ML, al Thagafi MA. Ascending paralysis due to myelitis in a newborn with congenital toxoplasmosis. J Neurol Sci 1996; 139 (01) 156-159
81 Malinger G, Werner H, Rodriguez Leonel JC. , et al. Prenatal brain imaging in congenital toxoplasmosis. Prenat Diagn 2011; 31 (09) 881-886
82 Dhombres F, Friszer S, Maurice P. , et al. Prognosis of fetal parenchymal cerebral lesions without ventriculomegaly in congenital toxoplasmosis infection. Fetal Diagn Ther 2017; 41 (01) 8-14
83 Kulkarni AM, Baskar S, Kulkarni ML. , et al. Fetal intracranial calcification: pseudo-TORCH phenotype and discussion of related phenotypes. Am J Med Genet A 2010; 152A (04) 930-937
84 Crow YJ, Livingston JH. Aicardi-Goutières syndrome: an important Mendelian mimic of congenital infection. Dev Med Child Neurol 2008; 50 (06) 410-416
85 Livingston JH, Stivaros S, van der Knaap MS, Crow YJ. Recognizable phenotypes associated with intracranial calcification. Dev Med Child Neurol 2013; 55 (01) 46-57
86 Livingston JH, Stivaros S, Warren D, Crow YJ. Intracranial calcification in childhood: a review of aetiologies and recognizable phenotypes. Dev Med Child Neurol 2014; 56 (07) 612-626