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BackgroundThe N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD).ObjectiveEvaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum.MethodsAdults (n = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed.ResultsA total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (>2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks.ConclusionAC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks.

Background: Remote assessment of neurological disability in people with multiple sclerosis (MS) could improve access to clinical care and efficiency of clinical research. Objective: To develop and validate a telemedicine-based MS disability examination that does not require an in-home examiner. Methods: Adults with MS were recruited after a standardized in-person Expanded Disability Status Scale (EDSS) evaluation, and within 1 week underwent a blinded televideo-enabled EDSS examination with a different clinician. EDSS and tele-EDSS scores were compared. Results: Overall, 41 adults participated (mean (standard deviation (SD)) age: 47.0 years (11.6); median EDSS: 2 (range: 0–7)); 37 required no in-home assistance for the tele-EDSS evaluation (e.g. help positioning camera). Mean difference between EDSS and tele-EDSS was 0.34 (95% confidence interval (CI): 0.07–0.61). For 88% of evaluations, tele-EDSS and EDSS scores were within 1 point (similar to reported in-person inter-rater differences). Unweighted kappa for agreement within 0.5 point was 0.72. Correlation for individual functional systems (FS) ranged from modest (vision: 0.37) to high (bowel/bladder: 0.79). Overall correlation between EDSS and tele-EDSS was 0.89 (p < 0.0001); and 0.98 (p < 0.0001) at EDSS range: 4–7. Conclusion: In this proof of principle study, disability evaluation in mild to moderate MS is feasible using telemedicine without an aide at the patient's location. [ABSTRACT FROM AUTHOR]

Background: Electronic medical records (EMR) data are increasingly used in research, but no studies have yet evaluated similarity between EMR and research-quality data and between characteristics of an EMR multiple sclerosis (MS) population and known natural MS history. Objectives: To (1) identify MS patients in an EMR system and extract clinical data, (2) compare EMR-extracted data with gold-standard research data, and (3) compare EMR MS population characteristics to expected MS natural history. Methods: Algorithms were implemented to identify MS patients from the University of California San Francisco EMR, de-identify the data and extract clinical variables. EMR-extracted data were compared to research cohort data in a subset of patients. Results: We identified 4142 MS patients via search of the EMR and extracted their clinical data with good accuracy. EMR and research values showed good concordance for Expanded Disability Status Scale (EDSS), timed-25-foot walk, and subtype. We replicated several expected MS epidemiological features from MS natural history including higher EDSS for progressive versus relapsing–remitting patients and for male versus female patients and increased EDSS with age at examination and disease duration. Conclusion: Large real-world cohorts algorithmically extracted from the EMR can expand opportunities for MS clinical research. [ABSTRACT FROM AUTHOR]

Objective: To assess retinal ganglion cell (RGC) injury and sex differences in axon loss in pediatric multiple sclerosis (MS). Methods: This is a cross-sectional evaluation of consecutive pediatric MS subjects and controls. Eyes with acute optic neuritis (ON) within 6 months of visit were excluded. Spectral domain optical coherence tomography (OCT) included peripapillary ring and macular scans with post-acquisition segmentation of retinal layers using automated software (Heidelberg v1.8.6.0). Generalized estimating equations (GEEs) measured associations of sex, history of ON, disease duration, and age with OCT outcomes. Results: In all, 53 MS subjects (100 eyes, median disease duration = 1.0 years, interquartile range (IQR) = 0.3, 2.5) were compared to 19 control subjects (38 eyes). Eyes with history of ON showed reduced retinal nerve fiber layer (RNFL: −26.8 µm, 95% confidence interval (CI) = −38.9, −14.8, p < 0.001) and 26% lower ganglion cell layer (GCL) volumes (−0.12 mm3, 95% CI = −0.16, −0.072, p < 0.001) compared to control eyes. Non-ON MS eyes had lower temporal RNFL (−11.9 µm, 95% CI = −18.6, −5.3, p < 0.001) and GCL volumes (−0.036 mm3, 95% CI = −0.06, −0.011, p = 0.004) than control eyes. In MS eyes, males versus females had lower global RNFL (−9.4 µm, 95% CI = −17.4, −1.33, p = 0.022) and in ON eyes had lower temporal quadrant RNFL (−9.6 µm, 95% CI = −15.1, −4.15, p = 0.001). Conclusion: Subclinical retinal injury occurs in pediatric-onset MS patients without a history of ON. As in adult-onset MS, substantial GCL thinning is present in eyes with prior ON. Finally, greater retinal axonal injury occurs in boys compared to girls. [ABSTRACT FROM AUTHOR]