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Background: Sensitive and specific biomarkers for use in progressive multiple sclerosis (MS) have not been established. We investigate neurofilament light (NfL) as a treatment response biomarker in progressive MS. Objective: To evaluate whether ibudilast 100 mg/day alters serum and cerebrospinal fluid (CSF) levels of NfL in progressive MS. Methods: In a protocol-defined exploratory analysis from a 2-year, phase 2 clinical trial of ibudilast in progressive MS (NCT01982942), serum samples were collected from 239 subjects and a subset contributed CSF and assayed using single-molecule assay (SIMOA) immunoassay. A mixed model for repeated measurements yielded log(NfL) as the response variable. Results: The geometric mean baseline serum NfL was 31.9 and 28.8 pg/mL in placebo and ibudilast groups, respectively. The geometric mean baseline CSF NfL was 1150.8 and 1290.3 pg/mL in placebo and ibudilast groups, respectively. Serum and CSF NfL correlations were r = 0.52 and r = 0.78 at weeks 48 and 96, respectively. Over 96 weeks, there was no between-group difference in NfL in either serum ( p = 0.76) or CSF ( p = 0.46). After controlling for factors that may affect NfL, no effect of ibudilast on NfL in either serum or CSF was observed. Conclusion: Ibudilast treatment was not associated with a change in either serum or CSF NfL.

Diffusion basis spectrum imaging (DBSI) models diffusion-weighted magnetic resonance imaging (MRI) signals as a combination of discrete anisotropic diffusion tensors and a spectrum of isotropic diffusion tensors. Here, we report the histopathological correlates of DBSI in the biopsied brain tissue of a patient with an inflammatory demyelinating lesion typical of multiple sclerosis (MS). Increased radial diffusivity (marker of demyelination), decreased fiber fraction (apparent axonal density), elevated nonrestricted isotropic fraction (marker of vasogenic edema), but unchanged axial diffusivity (marker of integrity of residual axons) seen in the lesion appeared consistent with histopathological findings of inflammatory demyelination with relative axonal sparing. Our report supports the application of DBSI as a biomarker in human studies of MS.

Background: The Expanded Disability Status Scale (EDSS) is the standard measure of disability in multiple sclerosis clinical trials. The EDSS has limited application in the clinical setting due to required completion time and scoring complexity. Systematically recording an objective, simplified, less time-intensive, and neurologist-derived disability score would be beneficial for patient care. Objective: To develop and validate a streamlined version of the Expanded Disability Status Scale (sEDSS) for clinical monitoring. Methods: The EDSS was modified by eliminating maneuvers with no impact on function, consolidating redundancies, and simplifying scoring. This sEDSS was refined and preliminarily validated using a pilot cohort of 102 patients. Subsequently, the sEDSS was retrospectively validated using 968 patients from the CombiRx trial. We evaluated correlation and agreement between each functional system as well as the overall sEDSS and EDSS. Results: The sEDSS correlated strongly with the EDSS, both overall (Spearman’s rho = 0.93) and for each functional system (Spearman’s rho 0.65–0.97). Correlation was slightly lower for functional systems where scoring was modified for consolidation and simplification. Conclusion: The sEDSS had strong agreement and correlation with the existing EDSS and can provide a useful measure of disability in clinical practice.

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) both affect spinal cord with notable differences in pathology. Objective: Determine the utility of diffusion tensor imaging (DTI) to differentiate the spinal cord lesions of NMO from MS within and outside T2 lesions. Methods: Subjects greater than or equal to 12 months from a clinical episode of transverse myelitis underwent a novel transaxial cervical spinal cord DTI sequence. Ten subjects with NMO, 10 with MS and 10 healthy controls were included. Results: Within T2 affected white matter regions, radial diffusivity was increased in both NMO and MS compared with healthy controls ( pConclusions: Higher radial diffusivity within spinal cord white matter tracts derived from diffusion tensor imaging were appreciated in NMO compared with MS, consistent with the known greater tissue destruction seen in NMO. DTI also detected tissue alterations outside T2 lesions and may be a surrogate of anterograde and retrograde degeneration.