Prospective evaluation of the brain in asymptomatic children with neurofibromatosis type 1: Relationship of macrocephaly to T1 relaxation changes andstructural brain abnormalities

BACKGROUND AND PURPOSE: Mutation of the neurofibromatosis type 1 (NF-1) gen e may be associated with abnormal growth control in the brain. Because macr ocephaly could be a sign of abnormal brain development and because 30% to 5 0% of children with NF-1 display macrocephaly in the absence of hydrocephal us, we sought to determine the relationship between macrocephaly and other brain abnormalities in young subjects with NF-1. These subjects sere Free o f brain tumor epilepsy, or other obvious neurologic problems. METHODS: We prospectively screened 18 neurologically asymptomatic subjects with NF-1, ages 6 to 16 gears, using clinical measures, psychometric testin g, conventional MR imaging, and quantitative MR imaging to measure T1. RESULTS: Cranial circumference was 2 or more SDs above the age norm in seve n (39%) of 18 subjects, a frequency of macrocephaly 17-fold higher than nor mal. Conventional MR imaging showed abnormalities in all IS children, altho ugh there were more extensive abnormalities in subjects with macrocephaly. Macrocephaly in NF-1 was associated with enlargement of multiple brain stru ctures, and brain T1 in macrocephalic subjects was reduced with respect to controls in the genu, frontal white matter, caudate, putamen, thalamus, and cortex, In normocephalic subjects, T1 was reduced only in the genu and spl enium, Volumetric analysis showed that macrocephaly was associated specific ally with enlargement of white matter volume. CONCLUSION: Neurologically asymptomatic children with NF-1 showed macroceph aly, cognitive deficit, enlarged brain structures, and abnormally low brain T1. Macrocephaly in children with NF-1 may be associated with characterist ic alterations in brain development, marked by more widespread and signific ant changes in T1, greater enlargement of midtime structures, and greater v olume of white matter.