Permeability of the blood–brain barrier predicts no evidence of disease activity at 2 years after natalizumab or fingolimod treatment in relapsing–remitting multiple sclerosis

Autor: Stig P. Cramer, Henrik Larsson, Jette L. Frederiksen, Helle J. Simonsen, Ian Galea, Aravinthan Varatharaj
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Annals of Neurology
Cramer, S P, Simonsen, H J, Varatharaj, A, Galea, I, Frederiksen, J L & Larsson, H B W 2018, ' Permeability of the blood–brain barrier predicts no evidence of disease activity at 2 years after natalizumab or fingolimod treatment in relapsing–remitting multiple sclerosis ', Annals of Neurology, vol. 83, no. 5, pp. 902-914 . https://doi.org/10.1002/ana.25219
ISSN: 1531-8249
0364-5134
Popis: Objective: To investigate whether blood–brain barrier (BBB) permeability, as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), can provide early detection of suboptimal treatment response in relapsing–remitting multiple sclerosis (RRMS). Methods: Thirty-five RRMS patients starting on fingolimod or natalizumab, drugs with a common effect of decreasing lymphocyte influx into the central nervous system, were scanned with DCE-MRI at 3T prior to treatment and at 3 and 6 months posttreatment. We calculated the influx constant Ki, a measure of BBB permeability, using the Patlak model. Suboptimal treatment response was defined as loss of no evidence of disease activity (NEDA) status after 2 years of treatment. Results: Subjects with loss of NEDA status at 2 years had a 51% higher mean Ki in normal-appearing white matter (NAWM) measured after 6 months of treatment, compared to subjects with maintained NEDA status (mean difference = 0.06ml/100g/min, 95% confidence interval [CI] = 0.02–0.09, p = 0.002). Ki in NAWM at 6 months was a good predictor of loss of NEDA status at 2 years (area under the curve = 0.84, 95% CI = 0.70–0.99, p = 0.003), and a value above 0.136ml/100/g/min yielded an odds ratio of 12.4 for suboptimal treatment response at 2 years, with a sensitivity of 73% and a specificity of 82%. Interpretation: Our results suggest that BBB permeability as measured by DCE-MRI reliably predicts suboptimal treatment response and is a surrogate marker of the state of health of the BBB. We find a predictive threshold for disease activity, which is remarkably identical in clinically isolated syndrome as previously reported and established RRMS as investigated here. Ann Neurol 2018;83:902–914.
Databáze: OpenAIRE
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