{
  "abstract": "Background Multiple sclerosis (MS) involves cortical injury, including cortical lesion (CL) development. Ibudilast treatment was found to slow progression of whole brain and cortical atrophy, but the effect of ibudilast on CLs is unknown. The present study aims to evaluate the treatment effect of ibudilast on CL development and whether the effect of ibudilast on brain atrophy is modified by CLs in primary-progressive MS (PPMS).Methods In this longitudinal study, we analysed data of 102 people with PPMS (ibudilast: n=49; placebo: n=53) from the Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis. CLs were identified on artificial intelligence-generated double inversion-recovery images created from T1 and T2 images at 3T MRI and rated at baseline and week 96. Atrophy was measured by cortical thickness and brain parenchymal fraction.Results CLs were detected in all participants with PPMS with a median count of 22 (11–34) in the ibudilast group and 28 (13–44) in the placebo group. At baseline, treatment groups did not differ in any brain volume measure or CL count. Higher CL counts at baseline were associated with higher CL formation during follow-up ( B(95% CI)=0.20 (0.12 to 0.29), p<0.001), independent of ibudilast treatment.Change in CL count did not differ between treatment groups (mean difference (SD)=0.07 (0.29), p=0.364). Protective effect of ibudilast on cortical thickness was more prominent in subjects with greater CL formation, but this relationship was not observed with whole brain atrophy.Conclusions Ibudilast treatment does not affect CL development in PPMS. Its protective effect on cortical thinning is more prominent with greater CL formation.Trial registration number NCT01982942.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Anatomy and Neurosciences, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Eva A Krijnen"
    },
    {
      "affiliations": [
        "Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA"
      ],
      "name": "Anne M Bruijn"
    },
    {
      "affiliations": [
        "Department of Biostatistics, Brown University, Providence, Rhode Island, USA"
      ],
      "name": "Ani Eloyan"
    },
    {
      "affiliations": [
        "Anatomy and Neurosciences, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands"
      ],
      "name": "Menno M Schoonheim"
    },
    {
      "affiliations": [
        "Neurology, Cleveland Clinic Foundation, Cleveland, Ohio, USA"
      ],
      "name": "Robert J Fox"
    },
    {
      "affiliations": [
        "Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA"
      ],
      "name": "Eric C Klawiter"
    }
  ],
  "title": "Evaluation of cortical pathology in primary-progressive multiple sclerosis: a post hoc analysis of the SPRINT-MS trial",
  "uid": "92d452ff-c6fc-5776-91d9-63603134d8c2"
}