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PEDIATRICS

Cerebral MR Imaging in Uninfected Children Born to HIV-Seropositive Mothers and Perinatally Exposed to Zidovudine

Marc Tardieua, Francis Brunelleb, Charles Raybaudc, William Ballf, Béatrice Barretd, Brigitte Pautarde, Eric Lachassinef, Marie-Jeanne Mayauxd and Stéphane Blanchee

a Department of Pediatric Neurology, Hôpital Bicêtre AP-HP, Le Kremlin Bicêtre
b Department of Pediatric Radiology, Hôpital Necker AP-HP, Paris
c Department of Neuroradiology, Hôpital de la Timone, Marseille
d Department of Epidemiology, Demographics, and Social Sciences, Amiens
e Department of Pediatrics, Hôpital Nord, Amiens
f Hôpital Jean Verdier AP-HP, Bondy
g Department of Pediatric Immunology and Hematology, France
h Department of Radiology, Cincinnati Children’s Hospital Medical Center, OH

Address reprint requests to Stéphane Blanche, MD, Unité d’Immunologie et d’Hématologie Pédiatrique, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75743 Paris cedex 15

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.