Contributions
Abstract: P552
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: “No evidence of disease activity”(NEDA), defined by absence of clinical events (relapses or EDSS worsening) and radiological activity (new/enlarging T2 or enhancing lesions), is the goal of therapy for MS. However, conventional MRI measures correlate modestly with disability and do not detect diffuse damage in normal-appearing tissue. Diffusion tensor imaging (DTI) quantitatively measures white matter (WM) integrity, yielding better correlation with disability. We recently presented data showing that NEDA patients exhibit significantly slower rates of change in fractional anistropy (FA) compared to those not meeting NEDA criteria, but suprisingly, the rate of change of mean diffusivity (MD) was similar in both groups. In order to study this discrepancy, we examined the rate of change in two other DTI parameters, axial diffusivity (AD, which corresponds to axonal loss) and radial diffusivity (RD, which corresponds to myelin loss).
Methods: We included RRMS patients who visited our MS center over a three month period, met NEDA criteria for ≥2 years, and whose MRIs included DTI data. Patients who did not meet NEDA criteria served as controls (EDA group). MRI sequences included T2-, T1-, FLAIR, and a single-shot echo-planar sequence for DTI. Tract based spatial statistics were used to create a WM skeleton and mean values of AD and RD were obtained over the skeleton. Annual rates of change were calculated.
Results: 85 RRMS patients were included, 39 of which met NEDA criteria. AD was stable over time in both NEDA and EDA groups, suggesting preserved axons. However, RD significantly increased over time at a yearly rate of 1.1% (p=0.0006) in the NEDA group and at a yearly rate of 1.5% (p< 0.0001) in the EDA group, suggesting ongoing myelin loss. While the EDA rate of deterioration was faster than that of the NEDA group, this did not reach statistical significance.
Conclusions: We previously showed that FA increases and MD decreases over time, even in the setting of NEDA. We now show RD increases significantly over time in the NEDA group, suggesting ongoing myelin loss even in the absence of overt disease activity, whereas AD is stable, suggesting preserved axonal fibers. While patients meeting NEDA criteria showed a somewhat slower rate of RD increase, this did not reach statistical significance. Taken together, this data demonstrates that DTI is more sensitive at detecting ongoing myelin loss than routine measures.
Disclosure:
Asaff Harel has received consulting fees from Teva pharmaceuticals.
Dylan Sperling has no relevant disclosures.
Achillefs Ntranos has no relevant disclosures.
Matilde Inglese has received research support from the National Institutes of Health, National MS Society, Novartis Pharmaceuticals, and Teva Neuroscience.
Abstract: P552
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: “No evidence of disease activity”(NEDA), defined by absence of clinical events (relapses or EDSS worsening) and radiological activity (new/enlarging T2 or enhancing lesions), is the goal of therapy for MS. However, conventional MRI measures correlate modestly with disability and do not detect diffuse damage in normal-appearing tissue. Diffusion tensor imaging (DTI) quantitatively measures white matter (WM) integrity, yielding better correlation with disability. We recently presented data showing that NEDA patients exhibit significantly slower rates of change in fractional anistropy (FA) compared to those not meeting NEDA criteria, but suprisingly, the rate of change of mean diffusivity (MD) was similar in both groups. In order to study this discrepancy, we examined the rate of change in two other DTI parameters, axial diffusivity (AD, which corresponds to axonal loss) and radial diffusivity (RD, which corresponds to myelin loss).
Methods: We included RRMS patients who visited our MS center over a three month period, met NEDA criteria for ≥2 years, and whose MRIs included DTI data. Patients who did not meet NEDA criteria served as controls (EDA group). MRI sequences included T2-, T1-, FLAIR, and a single-shot echo-planar sequence for DTI. Tract based spatial statistics were used to create a WM skeleton and mean values of AD and RD were obtained over the skeleton. Annual rates of change were calculated.
Results: 85 RRMS patients were included, 39 of which met NEDA criteria. AD was stable over time in both NEDA and EDA groups, suggesting preserved axons. However, RD significantly increased over time at a yearly rate of 1.1% (p=0.0006) in the NEDA group and at a yearly rate of 1.5% (p< 0.0001) in the EDA group, suggesting ongoing myelin loss. While the EDA rate of deterioration was faster than that of the NEDA group, this did not reach statistical significance.
Conclusions: We previously showed that FA increases and MD decreases over time, even in the setting of NEDA. We now show RD increases significantly over time in the NEDA group, suggesting ongoing myelin loss even in the absence of overt disease activity, whereas AD is stable, suggesting preserved axonal fibers. While patients meeting NEDA criteria showed a somewhat slower rate of RD increase, this did not reach statistical significance. Taken together, this data demonstrates that DTI is more sensitive at detecting ongoing myelin loss than routine measures.
Disclosure:
Asaff Harel has received consulting fees from Teva pharmaceuticals.
Dylan Sperling has no relevant disclosures.
Achillefs Ntranos has no relevant disclosures.
Matilde Inglese has received research support from the National Institutes of Health, National MS Society, Novartis Pharmaceuticals, and Teva Neuroscience.