Cerebral MR imaging in uninfected children born to HIV-seropositive mothers and perinatally exposed to zidovudine

Abstract

Background and purpose: Mitochondrial dysfunction has been reported in HIV-negative children perinatally exposed to zidovudine, a drug often used in HIV-seropositive mothers during pregnancy. The purpose of this study was to determine the incidence of cerebral MR imaging findings in HIV-uninfected children exposed to zidovudine who present with unexplained neurologic symptoms.

Methods: Two expert groups conducted a systematic, retrospective review of all cerebral MR images available in a multicentric, nationwide French prospective cohort of children born to HIV-seropositive mothers to identify imaging abnormalities. Experts were blinded to each others' interpretations, to the children's neurologic symptoms, and to laboratory evidence of mitochondrial dysfunction. The incidence of abnormalities was determined and compared with the neurologic presentation and laboratory evidence of mitochondrial dysfunction.

Results: MR images from 49 HIV-uninfected children (mean age, 26 months) were available for study. All children were perinatally exposed to zidovudine. Twenty-two had probable or established mitochondrial dysfunction according to their symptoms and laboratory data. Twenty-seven children without mitochondrial dysfunction presented with unexplained neurologic symptoms (n = 14) or nonneurologic symptoms (n = 7), and six were asymptomatic. Sixteen of 22 MR images in children with mitochondriopathy were considered abnormal in both independent analyses. Diffuse hyperintensity in the supratentorial white matter (n = 9) and in the tegmentum pons (n = 9) were the most frequent anomalies. Imaging abnormalities were often multifocal (n = 10) and sometimes associated with necrotic areas (n = 3) and volume loss (n = 8). Although 19 of 27 MR images of children without mitochondrial dysfunction were mainly normal, abnormal images were observed in five of 14 children with unexplained neurologic symptoms and in three of six asymptomatic children.

Conclusion: Images observed in children with antiretroviral-induced mitochondrial dysfunction are similar to those observed in congenital mitochondrial diseases. These images were also observed in symptomatic or asymptomatic children without evidence of systemic mitochondrial dysfunction.

Fig 1.

Image in a boy aged 1 year 5 month with cognitive delay, dystonia, and nystagmus. Results of muscular biopsy established mitochondrial dysfunction. Axial T2-weighted MR image shows diffuse hyperintensity in the periventricular white matter. Note bilateral areas of necrosis.

Fig 2.

Image in a boy aged 10 months with severe cognitive delay and repeated seizures. Results of muscular biopsy established mitochondrial dysfunction. Axial FLAIR MR image shows diffuse hyperintensity in the tegmentum pons, basilar pons, and cerebellar vermis.

Fig 3.

Image in an asymptomatic boy aged 2 years. Axial FLAIR MR image shows hyperintensity in the bilateral periventricular white matter in the posterior trigonal regions.

Fig 4.

Image in an asymptomatic boy aged 2 years. Axial T2-weighted MR image shows hyperintensity of the brainstem and around the dentate nuclei.