What is the role of neuroimaging (head ultrasound, brain Computed Tomography (CT), brain Magnetic Resonance Imaging (MRI)) in the early detection and diagnosis of congenital infections in asymptomatic newborns?

Role of Neuroimaging in Early Detection of Asymptomatic Congenital Infections

Brain MRI should be performed as the primary neuroimaging modality for asymptomatic newborns with suspected congenital infections, as it provides superior sensitivity for detecting white matter abnormalities, calcifications, and structural changes that predict neurodevelopmental outcomes, while avoiding radiation exposure associated with CT. 1, 2

Imaging Modality Selection and Timing

MRI as First-Line Imaging

• MRI with diffusion-weighted imaging (DWI) should be performed within 24-48 hours of suspected congenital infection diagnosis to detect early cerebral changes that may not be apparent on other modalities 2
• Brain MRI detects abnormal white matter signal intensity on T2-weighted and FLAIR sequences, which are characteristic findings in congenital infections 2
• MRI obviates the radiation risk associated with head CT, making it preferable for initial evaluation in asymptomatic infants 1
• In congenital CMV infection specifically, MRI shows higher positive predictive value compared to head ultrasound for detecting abnormalities associated with poor neurodevelopmental outcome 3

CT Scan Considerations

• Head CT should be considered when there is suspicion of congenital toxoplasmosis to evaluate for intracranial calcifications, ventriculomegaly, and hydrocephalus 1
• CT has superior sensitivity compared to ultrasound for detecting intracranial calcifications (a key finding in toxoplasmosis) 1
• However, CT should be reserved for specific indications due to radiation exposure concerns in neonates 1

Head Ultrasound Role and Limitations

• Head ultrasound has been used primarily in European cohorts where symptomatic congenital toxoplasmosis rates are lower 1
• Ultrasound has significantly lower sensitivity than CT for intracranial calcifications and may miss important abnormalities 1
• Despite being the safest technique, ultrasound performs less well in detecting brain abnormalities associated with poor neurodevelopmental outcomes 3
• In one study, 32% of asymptomatic CMV patients had abnormal ultrasound findings while CT and MRI were normal, but ultrasound also missed findings detected by other modalities 3

Specific Neuroimaging Patterns by Pathogen

Congenital Toxoplasmosis

• Randomly distributed intracranial calcifications are the hallmark finding, distinguishing toxoplasmosis from other congenital infections 2, 4
• Ventricular dilatation or hydrocephalus may be present, with punctate focal calcifications indicating severe disease 2
• White matter signal abnormalities on T2-weighted and FLAIR sequences are common 2
• Resolution or diminution of calcifications occurs in 75% of treated cases by 1 year of age, associated with improved neurologic function 2

Congenital Cytomegalovirus (CMV)

• Periventricular calcifications (rather than randomly distributed) are characteristic 4
• Microcephaly, ventriculomegaly, and pachygyria may be revealed by fetal MRI 4
• Abnormal white matter signal intensity on T2-weighted sequences is a common finding 2

Other Congenital Infections

• Herpes simplex virus encephalitis shows medial temporal lobe involvement as the hallmark finding 2
• Zika virus infection demonstrates severe microcephaly, brain atrophy, and cortical malformations 2, 4
• Rubella primarily manifests as microcephaly 2

Clinical Decision Algorithm for Asymptomatic Infants

High-Risk Asymptomatic Infants Requiring Immediate Imaging

Perform comprehensive neuroimaging (preferably MRI) at birth for asymptomatic infants with:

• Positive Toxoplasma IgM or IgA antibodies 1
• Maternal acute infection in second or third trimester without antepartum treatment 1
• Positive amniotic fluid PCR or abnormal fetal ultrasonographic findings 1

Lower-Risk Asymptomatic Infants

Consider deferring or using less intensive imaging for asymptomatic infants with:

• Maternal first-trimester infection with spiramycin treatment 1
• Negative amniotic fluid PCR and normal monthly fetal ultrasonography 1
• Negative Toxoplasma IgM and IgA at birth 1

Critical Pitfalls to Avoid

Imaging Interpretation Errors

• Normal neuroimaging does not automatically preclude the diagnosis or risk of congenital infection 1
• No neuroimaging examination shows a negative predictive value of 100% for poor neurodevelopmental outcome 3
• Neuroimaging findings cannot reliably distinguish between genetic and infectious causes of brain malformations; diagnosis requires correlation with maternal history, serologic testing, PCR studies, and CSF analysis 2

Timing and Follow-Up Considerations

• A comprehensive neuroimaging evaluation is mandatory in infants with congenital infections to decide on treatment and make prognostic evaluations 3
• Serial neuroimaging may be necessary, as subtle white matter lesions may be difficult to detect early due to rapid growth, myelination, and activity-dependent plasticity 1
• Repeated MRI scans are recommended at age 2 years for infants with initially normal findings but persistent motor or neurological abnormalities 1

Prognostic Value of Neuroimaging

Predicting Neurodevelopmental Outcomes

• Hydrocephalus ex vacuo with elevated CSF protein predicts poor outcome in toxoplasmosis 2
• Obstructive hydrocephalus requiring shunt still allows 75% chance of normal/near-normal neurodevelopment with treatment 2
• The extent of MRI abnormality correlates with severity of disease and guides treatment intensity decisions 5, 3

Treatment and Surveillance Implications

• Neuroimaging findings determine whether intensive 12-month treatment versus shorter 3-6 month regimens are indicated 1
• Imaging results guide the frequency of neurologic evaluations (every 2-3 months in first year for confirmed cases versus every 4-6 months for uncertain cases) 1