BERLIN—Widespread focal cortical damage at multiple sclerosis (MS) onset identifies patients likely to have frequent early relapses and a rapid development of progressive disease, which results from worsening global cortical pathology over time, according to a study presented at ECTRIMS 2018. The results provide a basis for patient stratification with the goal of therapeutic optimization. In addition, the data “highlight the importance of elucidating mechanisms involved in early cortical pathology,” according to the investigators.
Following Patients With Relapsing-Remitting MS
Among patients with relapsing-remitting MS, a high frequency of early relapses is associated with increased risk of developing severe disability, which suggests that early biologic mechanisms influence long-term disease evolution. Antonio Scalfari, MD, PhD, a consultant neurologist at Imperial College Healthcare in London, and colleagues sought to investigate the relationship between early cortical pathology, early relapses, and the risk of converting to secondary progressive MS.
Dr. Scalfari and colleagues examined 219 patients with relapsing-remitting MS. Participants had one (n = 116), two (n = 53), or three or more (n = 50) relapses during the first two years. Follow-up lasted for a mean of 7.9 years. The researchers assessed the number of cortical lesions and white matter lesions and the rate of cortical thinning using 3D double inversion recovery, 3D T1-weighted imaging, and Freesurfer analysis.
Cortical Lesions Predicted Cortical Thinning
During the observation period, 59 (27%) patients converted to secondary progressive MS in a mean of 6.1 years. At disease onset, the investigators detected 674 cortical lesions in 166 (76%) patients. A larger number of cortical lesions was associated with a significantly higher risk of secondary progressive MS. The hazard ratios (HR) for secondary progressive MS were 2.16 for patients with two lesions, 4.79 for patients with five lesions, and 12.3 for patients with seven lesions. A large number of cortical lesions also was associated with shorter latency to secondary progressive MS and a faster rate of global cortical thinning. The mean loss per year was 0.93% for patients with no lesions, 0.99% for patients with one to three lesions, 1.13% for patients with four to six lesions, and 1.33% for patients with seven or more lesions. In the group with no cortical lesions (n = 53), no patients entered the secondary progressive phase, and four reached an Expanded Disability Status Scale score of 4.
Patients with a high number of early relapses, compared with those with low and moderate numbers, had a larger volume of white matter lesions and cortical lesions at onset. The mean volumes of cortical lesions were 181.6 mm3, 386.8 mm3, and 544.0 mm3 for patients with one, two, and three or more early relapses, respectively. Patients with a high number of early relapses also accrued more cortical lesions (mean cortical lesion volumes were 118.8 mm3, 138.8 mm3, and 790.5 mm3 for patients with one, two, and three or more early relapses, respectively), had a faster rate of cortical atrophy (mean loss/year was 0.47%, 0.79%, and 0.94% for patients with one, two, and three or more early relapses, respectively), and entered the secondary progressive phase more rapidly.
In the multivariate model, older age at onset (HR, 1.97), a larger baseline cortical lesion (HR, 2.21) and white matter lesion (HR, 1.32) volume, early changes of global cortical thickness (HR, 1.36), and three or more early relapses (HR, 6.08) independently predicted a higher probability of secondary progressive MS.