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Objective To prospectively determine the value of optical coherence tomography (OCT) as a surrogate outcome measure for the progression of myelopathy in males with adrenoleukodystrophy. Methods Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness were measured at baseline, 1‐ and 2‐year follow‐up in patients and age‐matched controls. We assessed the severity of myelopathy with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up‐and‐go. Linear mixed model analysis was used to compare changes in retinal layer thickness of patients to controls. In addition, we correlated changes in retinal layer thickness with changes in clinical parameters. Results Longitudinal data were available for 28 patients and 29 controls. Peripapillary RNFL (pRNFL) thickness decreased significantly in patients compared to controls (−1.75µm, p = 0.001), whereas change in macular GCL and RNFL was not different between groups. Analysis of the symptomatic subgroup showed that, apart from a similar decrease in pRNFL thickness, GCL thickness decreased significantly (−0.55 µm, p = 0.014). There were moderately strong correlations between changes in retinal layer thickness and changes in clinical parameters of severity of myelopathy. Interpretation This prospective study demonstrates the potential of OCT‐measured retinal neurodegeneration as a surrogate outcome measure for the progression of myelopathy in adrenoleukodystrophy. As differences were small, our findings need to be confirmed with longer follow‐up and/or in a larger patient sample.

Objective: To explore the potential of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of spinal cord degeneration in adrenoleukodystrophy, as objective treatment-outcome parameters are needed. Methods: Plasma NfL and GFAP levels were measured in 45 male and 47 female ALD patients and compared to a reference cohort of 73 healthy controls. For male patients, cerebrospinal fluid (CSF) samples (n = 33) and 1-year (n = 39) and 2-year (n = 18) follow-up data were also collected. Severity of myelopathy was assessed with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up-and-go. Results: NfL and GFAP levels were higher in male (P 2) NfL = 0.49, GFAP = 0.13) and female (P

In this observational study, 159 patients with multiple sclerosis received personalized dosing of ocrelizumab incentivized by the COVID-19 pandemic. Re-dosing was scheduled when CD19 B-cell count was ⩾10 cells/µL (starting 24 weeks after the previous dose, repeated 4-weekly). Median interval until re-dosing or last B-cell count was 34 [30–38] weeks. No clinical relapses were reported and a minority of patients showed Expanded Disability Status Scale (EDSS) progression. Monthly serum neurofilament light levels remained stable during extended intervals. Two (1.9%) of 107 patients with a follow-up magnetic resonance imaging (MRI) scan showed radiological disease activity. Personalized dosing of ocrelizumab could significantly extend intervals with low short-term disease activity incidence, encouraging future research on long-term safety and efficacy.

Background Progressive myelopathy is the main cause of disability in adrenoleukodystrophy (ALD). Development of therapies is hampered by a lack of quantitative outcome measures. In this study, we investigated whether myelopathy in ALD is associated with retinal neurodegeneration on optical coherence tomography (OCT), which could serve as a surrogate outcome measure. Methods Sixty-two patients (29 men and 33 women) and 70 age-matched and sex-matched controls (33 men and 37 women) were included in this cross-sectional study. We compared retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness between ALD patients and controls. In addition, we correlated these OCT measurements with clinical parameters of severity of myelopathy. Results Patients had significantly thinner RNFL (male group, p p p p ≤ 0.002) and in pRNFL thickness (superior and temporal quadrant) in both male (p ≤ 0.02) and the female (p ≤ 0.02) groups. Neuroretinal layer thickness correlated moderately with severity of myelopathy in men (correlation coefficients between 0.29–0.55, p Conclusions These results suggest that neurodegeneration of the spinal cord in ALD is reflected in the retina of patients with ALD. Therefore, OCT could be valuable as an outcome measure for the myelopathy of ALD. Additional longitudinal studies are ongoing.

ObjectiveTo prospectively determine the potential of diffusion MRI (dMRI) of the cervical spinal cord and the corticospinal tracts in brain as surrogate outcome measure for progression of myelopathy in men with adrenoleukodystrophy, as better outcome measures to quantify progression of myelopathy would enable clinical trials with fewer patients and shorter follow-up.MethodsClinical assessment of myelopathy included Expanded Disability Status Scale (EDSS), Severity Scoring System for Progressive Myelopathy (SSPROM), Timed Up-and-Go, and 6-Minute Walk Test. Applied dMRI metrics included fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity.ResultsData were available for 33 controls and 52 patients. First, cross-sectionally, differences between groups (controls vs patients; controls vs asymptomatic patients vs symptomatic patients) were statistically significant for fractional anisotropy, mean diffusivity, and radial diffusivity in spinal cord and brain corticospinal tracts (effect size 0.31–0.68). Correlations between dMRI metrics and clinical measures were moderate to strong (correlation coefficient 0.35–0.60). Second, longitudinally (n = 36), change on clinical measures was significant after 2-year follow-up for EDSS, SSPROM, and Timed Up-and-Go (p≤ 0.021, effect size ≤0.14). Change on brain fractional anisotropy and radial diffusivity was slightly larger (p≤ 0.002, effect sizes 0.16–0.28). In addition, a statistically significant change was detectable in asymptomatic patients using brain dMRI and not using the clinical measures. Change on clinical measures did not correlate to change on dMRI metrics.ConclusionAlthough effect sizes were small, our prospective data illustrate the potential of dMRI as surrogate outcome measure for progression of myelopathy in men with adrenoleukodystrophy.

Males with adrenoleukodystrophy develop progressive myelopathy causing severe disability later in life. No treatment is currently available, but new disease-modifying therapies are under development. Knowledge of the natural history of the myelopathy is of paramount importance for evaluation of these therapies in clinical trials, but prospective data on disease progression are lacking. We performed a prospective observational cohort study to quantify disease progression over 2 years of follow-up. Signs and symptoms, functional outcome measures and patient-reported outcomes were assessed at baseline, 1 and 2 years of follow-up. We included 46 male adrenoleukodystrophy patients (median age 45.5 years, range 16-71). Frequency of myelopathy at baseline increased with age from 30.8% (50 years). Disease progression was measured in the patients who were symptomatic at baseline (n = 24) or became symptomatic during follow-up (n = 1). Significant progression was detected with the functional outcome measures and quantitative vibration measurements. Over 2 years of follow-up, Expanded Disability Status Score increased by 0.34 points (P = 0.034), Severity Scoring system for Progressive Myelopathy decreased by 2.78 points (P = 0.013), timed up-and-go increased by 0.82 s (P = 0.032) and quantitative vibration measurement at the hallux decreased by 0.57 points (P = 0.040). Changes over 1-year follow-up were not significant, except for the 6-minute walk test that decreased by 19.67 meters over 1 year (P = 0.019). None of the patient-reported outcomes were able to detect disease progression. Our data show that progression of myelopathy in adrenoleukodystrophy can be quantified using practical and clinically relevant outcome measures. These results will help in the design of clinical trials and the development of new biomarkers for the myelopathy of adrenoleukodystrophy.10.1093/brain/awy299_video1awy299media15995811923001.

Background Progressive myelopathy is the main cause of disability in adrenoleukodystrophy (ALD). Development of therapies is hampered by a lack of quantitative outcome measures. In this study, we investigated whether myelopathy in ALD is associated with retinal neurodegeneration on optical coherence tomography (OCT), which could serve as a surrogate outcome measure. Methods Sixty-two patients (29 men and 33 women) and 70 age-matched and sex-matched controls (33 men and 37 women) were included in this cross-sectional study. We compared retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness between ALD patients and controls. In addition, we correlated these OCT measurements with clinical parameters of severity of myelopathy. Results Patients had significantly thinner RNFL (male group, p