Linear brain atrophy measures in multiple sclerosis and clinically isolated syndromes: a 30-year follow-up

ObjectiveTo determine 30-year brain atrophy rates following clinically isolated syndromes and the relationship of atrophy in the first 5 years and clinical outcomes 25 years later.MethodsA cohort of 132 people who presented with a clinically isolated syndrome suggestive of multiple sclerosis (MS) were recruited between 1984–1987. Clinical and MRI data were collected prospectively over 30 years. Widths of the third ventricle and the medulla oblongata were used as linear atrophy measures.ResultsAt 30 years, 27 participants remained classified as having had a clinically isolated syndrome, 34 converted to relapsing remitting MS, 26 to secondary progressive MS and 16 had died due to MS. The mean age at baseline was 31.7 years (SD 7.5) and the mean disease duration was 30.8 years (SD 0.9). Change in medullary and third ventricular width within the first 5 years, allowing for white matter lesion accrual and Expanded Disability Status Scale increases over the same period, predicted clinical outcome measures at 30 years. 1 mm of medullary atrophy within the first 5 years increased the risk for secondary progressive MS or MS related death by 30 years by 583% (OR 5.83, 95% CI 1.74 to 19.61, p<0.005), using logistic regression.ConclusionsOur findings show that brain regional atrophy within 5 years of a clinically isolated syndrome predicts progressive MS or a related death, and disability 25 years later.

Prognostic value of serum neurofilaments in patients with clinically isolated syndromes

ObjectiveTo assess the prognostic role of serum neurofilament light chains (NfL) for clinically defined multiple sclerosis (CDMS) and McDonald 2017 multiple sclerosis (MS) in patients with clinically isolated syndromes (CIS).MethodsWe retrospectively analyzed data of patients admitted to our neurologic department between 2000 and 2015 for a first demyelinating event. We evaluated baseline serum NfL in addition to CSF, MRI, and clinical data.ResultsAmong 222 patients who were enrolled (mean follow-up 100.6 months), 45 patients (20%) developed CDMS and 141 patients (63.5%) developed 2017 MS at 2 years. Serum NfL (median 22.0, interquartile range 11.6–40.4 pg/mL) was noticeably increased in patients with a recent relapse, with a high number of T2 and gadolinium-enhancing lesions at baseline MRI. Serum NfL was prognostic for both CDMS and McDonald 2017 MS, with a threefold and a twofold respective reduction in CDMS and 2017 MS risk in those patients with low and extremely low levels of NfL. The results remained unchanged subsequent to adjustment for such established MS prognostic factors as oligoclonal bands, Gd-enhancing lesions, and a high T2 lesion load at baseline MRI. NfL was associated with disability at baseline but not at follow-up.ConclusionsSerum NfL have a prognostic value for CIS patient conversion to MS. NfL might play a twin role as biomarker in MS as peak level measurements can act as a quantitative marker of serious inflammatory activity, while steady-state levels can be a reflection of neurodegenerative and chronic inflammatory processes.