Hypophosphatemia is Associated with the Serial Administration of Triple-Dose Gadolinium to Patients for Brain MRI.

BACKGROUND AND PURPOSE: The purpose of this study is to report a metabolic abnormality associated with frequent, triple-dose Gadolinium (TdGd) use in MS patients during BECOME trial. METHODS: Potential clinical adverse events and lab abnormalities were monitored at each monthly MRI visit. Hypophosphatemia was defined as phosphate <2.5 mg/dL. Statistical analysis included McNemar's test for pairwise comparisons across visits and generalized estimating equations (GEE) to fit models over time. RESULTS: Eight hundred seventy seven phosphate values were analyzed from the first 12 months. Compared with 4% of subjects at screening, an average of 15.1% (95% confidence interval (CI): 11.4%-19.7%) of patients had hypophosphatemia at visits from months 1 to 12, during which subjects received serial TdGd. Forty four of seventy five (59%) patients developed hypophosphatemia at least once. We also found a significant increasing trend in hypophosphatemia by visit when treatment groups were evaluated together or separately (p < .001). There was a statistically significant decrease in frequency to 9.8% (95% CI: 4.6-19.8%) by month 24 (p = .005) coinciding with a period of less frequent gadolinium administration. CONCLUSIONS: Serial TdGd in MS patients, unrelated to immunomodulatory treatment, was associated with increased frequency of hypophosphatemia that progressed with cumulative triple-dose and markedly decreased in second year, with less frequent triple-dose administration.

Impact of inflammation on brain volume in multiple sclerosis.

OBJECTIVE: To study changes in brain volume measured monthly in patients treated for relapsing multiple sclerosis due to loss of tissue and the appearance of inflammation. DESIGN AND PATIENTS: The results from T2/fluid-attenuated inversion recovery axial images from 13 consecutive monthly 3-T brain magnetic resonance imaging tests conducted on 74 patients diagnosed with relapsing multiple sclerosis in the BECOME study were used to calculate whole brain volumes using automated software analysis tools. The patients had been randomized to receive treatment with interferon beta-1b or glatiramer acetate. Ongoing inflammation was studied by counting the number of combined active lesions and measuring the volume of gadolinium enhancement. A mixed-effects model was used to analyze brain volumes over time. RESULTS: There was a significant decrease in brain volume over time but there was no difference in its rate of change by age, sex, frequency of ongoing inflammation, multiple sclerosis type, or randomized treatment assignment. The mean rate of brain volume change per month from multivariable models was -1.1 cm(3) (95% CI, -1.5 to -0.6) and during times of magnetic resonance imaging activity, it increased transiently by an average of 1.2 cm(3)/lesion (95% CI, 0.7 to 1.7) and 7.1 cm(3)/1 cm(3 )of gadolinium volume. In a model with both measures, combined active lesions were independent predictors of brain volume but gadolinium volume was not. CONCLUSION: Two major changes in brain volume occur in patients with relapsing multiple sclerosis, a steady decrease likely due to tissue loss with overlapping transient increases due to the appearance of inflammation.