#ECTRIMS2018 — In CIS Patients, Early Lesions in Specific Brain Area Linked to Worse Disability 30 Years Later, Study Shows

Lesions in the infratentorial region of the brain at the onset of clinically isolated syndrome (CIS) and lesions in white matter one year after CIS onset are associated with worse disability 30 years later, a study reports.

The study, “Early MRI predictors of long-term multiple sclerosis outcomes: a 30-year follow-up study of people presenting with clinically isolated syndromes,” was presented at the 34^th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place through Friday in Berlin.

Karen Chung, from the NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology in the United Kingdom, presented the data.

Unlike most multiple sclerosis (MS) patients who experience neurological impairment over time, some develop little disability even after 20 or more years. Given the scarcity of magnetic resonance imaging (MRI) studies on predictors of long-term MS outcomes, a team from the U.K. and the Netherlands assessed early MRI predictors of disability 30 years after the onset of CIS.

CIS is a neurological episode lasting at least 24 hours, and is characterized by inflammation and loss of the protective layer of nerve fibers — called myelin — often preceding MS development.

“Clinical outcomes after a CIS are very variable,” Chung said.

Specifically, the team investigated MRI predictors using, as the threshold of disability, an Expanded Disability Status Scale (EDSS) score of 3.5 or lower — meaning minimal to moderate disability and no mobility impairment — 30 years after CIS onset.

The study used data from the 30-year follow-up of the first London CIS group. It assessed specific MRI-detected brain lesions and lesion location at baseline and at one- and five-year scans.

Possible lesion locations were periventricular (around the brain ventricles, which are interconnected cavities filled with a liquid called cerebrospinal fluid), juxtacortical (next to the cerebral cortex, implicated in diverse functions, such as memory and motor control), deep white matter (which is made of nerve fibers), and infratentorial (which contains the cerebellum and has been previously linked with long-term disability in MS).

Disease course at 30 years was classified as CIS, MS with an EDSS score 3.5 or less, MS with an EDSS score higher than 3.5, or death due to MS (EDSS score of 10).

Outcomes were known for 120 of the initial 132 participants (91%) after a mean period of 30.1 years.

At 30 years, 40 participants had CIS (33%), and 80 had MS (67%). Among those with MS, 35 (44%) had relapsing-remitting MS, while 26 (33%) had secondary progressive MS. MS contributed to the death of 16 patients (20%), and three others (4%) died of unknown or unrelated causes.

In total, 32 patients (27%) had an EDSS score of 3.5 or less, all of whom had not progressed beyond RRMS.

Infratentorial lesions at baseline and deep white matter lesions at one year were the most significant early MRI predictors correlating with an EDSS score greater than 3.5 at 30 years.

The estimated risk of an EDSS score greater than 3.5 at 30 years was 13% in patients without baseline infratentorial and deep white matter lesions one year after CIS, and 94% in those with both baseline infratentorial and one-year deep white matter lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher levels of disability three decades later,” Chung concluded.