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Abstract: Computerized tomography (CT) of the brain was performed in 10 of 11 consecutive infants with neonatal lupus erythematosus (NLE) (five boys and six girls). Ten of the 11 infants had brain neurosonography. Nine of 10 infants had abnormal CT scans. There was diffuse, markedly reduced attenuation of the cerebral white matter in four infants studied in the first week of life, and also in an infant 5 weeks of age. Patchy reduced subcortical white matter attenuation was observed in another 5-week-old infant. Basal ganglia calcifications were present in two infants at 2 months of age, one of whom also had mild ventriculomegaly. A patient with macrocephaly studied at 4 months of age had enlarged ventricles and subarachnoid spaces consistent with benign macrocephaly of infancy. Cerebral ultrasound examination was abnormal in all five infants studied in the first week of life and in one infant at 2 months of age. Findings included subependymal cysts (4), echogenic white matter (3), and echogenic lenticulostriate vessels (3). Apart from one case of macrocephaly, there was no clinical evidence of neurologic disease and the subsequent development of these infants has been normal. Subclinical central nervous system (CNS) disease in NLE is likely to be a transient phenomenon that resolves as maternal antibodies are cleared from the infant's circulation. It is important to be aware of these neuroimaging abnormalities to avoid misdiagnosis of congenital viral infection in a newborn with multisystem NLE. The potential for neurologic sequelae is uncertain.