Contributions
Abstract: 155
Type: Scientific Session
Abstract Category: Clinical aspects of MS - Natural course
Introduction: Among relapsing remitting (RR) MS patients, high frequency of early relapses associates with higher risk of developing severe disability, suggesting that early biological mechanisms influence the long-term disease evolution. We set out to investigate the relationship between early cortical pathology, early relapses (ER) and the risk of converting to secondary progressive (SP) MS.
Methods: By using 3D Double Inversion Recovery, 3DT1 weighted imaging and Freesurfer analysis, we assessed the number of cortical (CLs) and white matter (WM) lesions, and the rate of cortical thinning, among 219 RR MS patients with 1 (n=116), 2 (n=53) and ≥3 (n = 50) relapses during the first 2 years, followed for 7.9 mean years.
Results: Within the observation period, 59 (27%) patients converted to SPMS in 6.1 mean years. At the disease onset, we detected 674 CLs in 166 (76%) patients; a larger number of CLs associated with a significantly higher risk of SP (HR 2.16, 4.79 and 12.3, for 2, 5 and 7 lesions, respectively; p< 0.001), shorter latency to SP and faster rate of global cortical thinning (mean loss/year -0.93%, -0.99%, -1.13%, -1.33%, for 0, 1-3, 4-6, ≥7 lesions, respectively; p< 0.001). In the group with no CLs (n=53) none of patients entered the SP phase and only few (n=4) reached EDSS 4. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset (mean mm3 CLs volume 181.6, 386.8, 544.0 for 1, 2 and ≥3 ER, respectively; p< 0.001), accrued more CLs (mean mm3 CLs volume 118.8, 138.8, 790.5 for 1, 2 and ≥3 ER, respectively; p< 0.001), experienced faster rate of cortical atrophy (mean loss/year -0.47%, -0.79%, -0.94% for 1, 2 and ≥3 ER, respectively; p< 0.001) over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p< 0.001), a larger baseline CLs (HR 2.21, p=0.005) and WM lesions (HR 1.32, p=0.03) volume, early changes of global Cth (HR 1.36, p=0.03), and ≥3 ER (HR 6.08, p< 0.001) independently predicted a higher probability of SP.
Conclusions: Widespread focal cortical damage at onset distinguishes patients destined to have frequent early relapses and a rapid occurrence of the progressive course, which is driven by the worsening global cortical pathology over time. These results provided a basis for patients' stratification aimed at therapeutic optimization and highlight the importance of elucidating mechanisms involved in the early cortical pathology.
Disclosure: Antonio Scalfari: nothing to disclose
Chiara Romualdi: nothing to disclose
Roberta Magliozzi: nothing to disclose
Miriam Mattoscio: nothing to disclose
Paolo Muraro: nothing to disclose
Richard Nicholas: nothing to disclose
Massimilano Calabrese: nothing to disclose
Abstract: 155
Type: Scientific Session
Abstract Category: Clinical aspects of MS - Natural course
Introduction: Among relapsing remitting (RR) MS patients, high frequency of early relapses associates with higher risk of developing severe disability, suggesting that early biological mechanisms influence the long-term disease evolution. We set out to investigate the relationship between early cortical pathology, early relapses (ER) and the risk of converting to secondary progressive (SP) MS.
Methods: By using 3D Double Inversion Recovery, 3DT1 weighted imaging and Freesurfer analysis, we assessed the number of cortical (CLs) and white matter (WM) lesions, and the rate of cortical thinning, among 219 RR MS patients with 1 (n=116), 2 (n=53) and ≥3 (n = 50) relapses during the first 2 years, followed for 7.9 mean years.
Results: Within the observation period, 59 (27%) patients converted to SPMS in 6.1 mean years. At the disease onset, we detected 674 CLs in 166 (76%) patients; a larger number of CLs associated with a significantly higher risk of SP (HR 2.16, 4.79 and 12.3, for 2, 5 and 7 lesions, respectively; p< 0.001), shorter latency to SP and faster rate of global cortical thinning (mean loss/year -0.93%, -0.99%, -1.13%, -1.33%, for 0, 1-3, 4-6, ≥7 lesions, respectively; p< 0.001). In the group with no CLs (n=53) none of patients entered the SP phase and only few (n=4) reached EDSS 4. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset (mean mm3 CLs volume 181.6, 386.8, 544.0 for 1, 2 and ≥3 ER, respectively; p< 0.001), accrued more CLs (mean mm3 CLs volume 118.8, 138.8, 790.5 for 1, 2 and ≥3 ER, respectively; p< 0.001), experienced faster rate of cortical atrophy (mean loss/year -0.47%, -0.79%, -0.94% for 1, 2 and ≥3 ER, respectively; p< 0.001) over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p< 0.001), a larger baseline CLs (HR 2.21, p=0.005) and WM lesions (HR 1.32, p=0.03) volume, early changes of global Cth (HR 1.36, p=0.03), and ≥3 ER (HR 6.08, p< 0.001) independently predicted a higher probability of SP.
Conclusions: Widespread focal cortical damage at onset distinguishes patients destined to have frequent early relapses and a rapid occurrence of the progressive course, which is driven by the worsening global cortical pathology over time. These results provided a basis for patients' stratification aimed at therapeutic optimization and highlight the importance of elucidating mechanisms involved in the early cortical pathology.
Disclosure: Antonio Scalfari: nothing to disclose
Chiara Romualdi: nothing to disclose
Roberta Magliozzi: nothing to disclose
Miriam Mattoscio: nothing to disclose
Paolo Muraro: nothing to disclose
Richard Nicholas: nothing to disclose
Massimilano Calabrese: nothing to disclose