ObjectiveNeurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single‐molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).MethodssNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross‐sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow‐up = 3.1 years, interquartile range [IQR] = 2.0–4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes.ResultssNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2–65.3) or both brain and spinal gadolinium‐enhancing lesions (62.5pg/ml, IQR = 42.7–71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9–41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease‐modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC‐based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval [CI] = 1.21–3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07–5.42, p = 0.034).InterpretationThese results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857–870

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ObjectiveTo assess whether chronic white matter inflammation in multiple sclerosis (MS) patients - as detected in-vivo by paramagnetic rim MRI lesions (PRL) - is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuro-axonal damage.MethodsIn 118 MS patients with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathological evaluation was performed in 25 MS lesions from 20 additional autopsy MS patients.ResultsIn univariable analyses, participants with ≥2 PRL (“PRL ≥2”, n=43) compared to those with ≤1 PRL (“PRL 0–1,” n=75) had higher age-adjusted sNfL percentiles (median, 91 and 68; p<0.001) and higher MS disease severity scale (MSSS median, 4.3 and 2.4; p=0.003). In multivariable analyses, sNfL percentile levels were higher in PRL ≥2 cases (βadd: 16.3; 95% CI: 4.6–28.0; p<0.01), whereas disease-modifying treatment (DMT), EDSS, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRL (n=30; βadd: 30.4; 95% CI, 15.6–45.2; p<0.01). Subsequent multivariable analysis revealed that PRL ≥2 cases had also higher MSSS (βadd: 1.1; 95% CI, 0.3–1.9; p<0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center: p=0.004 and p=0.0002, respectively).InterpretationChronic white matter inflammation was associated with increased levels of sNfL and disease severity in non-acute MS patients, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.

Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in PD.

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Level IV, prospective observational study.

RivLev did not differ between patients with AIS and ICH. Half of the patients with AIS under rivaroxaban had a RivLev low enough to consider thrombolysis. In ICH patients, two-thirds had a RivLev high enough to meet the eligibility for the use of a specific reversal agent. INR thresholds perform poorly to inform treatment decisions in individual patients. Ann Neurol 2018;83:451-459.