Diffusion-tensor imaging assessment of white matter maturation in childhood and adolescence.

OBJECTIVE: The purpose of this study was to test a first hypothesis that fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values continue to change in late childhood and adolescence and a second hypothesis that less mature white matter (WM) regions have a higher rate of change than WM regions that are relatively more mature. SUBJECTS AND METHODS: Eighty-seven healthy children (50 girls, 37 boys; mean age, 11.2 ± 3.6 years; range, 4.2-17.7 years) underwent six-direction diffusion-tensor imaging with a 3-T MRI system. Three neuroradiologists independently drew regions of interest in 10 WM regions and measured FA and ADC values. To test the first hypothesis, we correlated these values with subject age by linear regression analysis (p < 0.05). To test the second hypothesis, we determined whether regions with lower FA and higher ADC in the 4- to 7-year old group had a higher slope of FA increase and ADC decrease over the entire age range. For this assessment, we used linear regression analysis (p < 0.05) and curve fitting. RESULTS: In the test of the first hypothesis, increases in FA with age were noted in all WM regions and were statistically significant in six regions. Decreases in ADC values with age were noted in all brain regions except the genu of the corpus callosum. In all other regions except the splenium of the corpus callosum, the decreases were statistically significant. In the test of the second hypothesis, the relation between FA in the 4- to 7-year-old subjects and the FA increase in the entire sample was best described with a linear equation. The rate of age-related FA increase tended to be greater with lower initial FA (r = -0.384, p = 0.271). The relation between ADC in the 4- to 7-year-old subjects and ADC decrease in the entire population was best described with a second-order equation. The rate of age-related ADC decrease tended to be greater with higher initial ADC (r = 0.846, p = 0.001). For ADC values of 100 or less at age 4-7 years, the rate of ADC change with age tended to be decrease as initial ADC increased. CONCLUSION: In general, both hypotheses were verified. Overall, FA values continue to increase and ADC values continue to decrease during childhood and adolescence. The most rapid changes were found in WM regions that were least mature in the first few years of the study period.

Hyperlactataemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors.

OBJECTIVE: To evaluate the prevalence, outcome and possible risk factors for hyperlactataemia and lactic acidosis in HIV-positive persons receiving antiretroviral therapy. METHODS: Cross-sectional and longitudinal data from a prospectively collected clinical database. Associations with antiretroviral regimen, clinical and laboratory parameters were assessed using univariate and multivariate Cox's proportional hazards model. RESULTS: Patients naive to therapy and patients on current therapy for a minimum of 4 months were assessed. Median lactate was 1.1 mol/l in 253 untreated individuals and 1.4 mmol/l in 1239 patients stable on therapy for at least 4 months. At least two on-therapy samples were available for 750 of the 1239 individuals, taken a median 92 days apart. Lactate measurement showed a low positive predictive value of 38.9% but a high negative predictive value (98%) for normal values. Lactate was elevated > or = 2.4 mmol/l in 102 individuals on at least one occasion. In the multivariate Cox's proportional hazards model, no demographic characteristics were associated with hyperlactataemia. Didanosine-containing regimens doubled the relative hazard of hyperlactataemia compared with those sparing didanosine. Abacavir-containing regimens reduced the hazard of hyperlactataemia. Choice of thymidine analogue did not influence risk. Hyperlactataemia was associated with acid-base disturbance. Use of didanosine and female sex were over-represented amongst nine patients with severe hyperlactataemia (> 5 mmol/l) or lactic acidosis. CONCLUSIONS: Screening of lactate is of limited use in asymptomatic individuals on antiretroviral therapy. Raised lactate represents part of a spectrum of lactate and acid-base disturbance that infrequently includes lactic acidosis. Didanosine appears associated with an increased risk of hyperlactataemia.