Progression of myelopathy in males with adrenoleukodystrophy: towards clinical trial readiness.

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% (<30 years) to 94.7% (>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.

Rapid Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review and Meta-analysis.

Rapid diagnosis of respiratory virus infections contributes to patient care. This systematic review evaluates the diagnostic accuracy of rapid tests for the detection of respiratory viruses. We searched Medline and EMBASE for studies evaluating these tests against polymerase chain reaction as the reference standard. Of 179 studies included, 134 evaluated rapid tests for influenza viruses, 32 for respiratory syncytial virus (RSV), and 13 for other respiratory viruses. We used the bivariate random effects model for quantitative meta-analysis of the results. Most tests detected only influenza viruses or RSV. Summary sensitivity and specificity estimates of tests for influenza were 61.1% and 98.9%. For RSV, summary sensitivity was 75.3%, and specificity, 98.7%. We assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Because of incomplete reporting, the risk of bias was often unclear. Despite their intended use at the point of care, 26.3% of tests were evaluated in a laboratory setting. Although newly developed tests seem more sensitive, high-quality evaluations of these tests are lacking.

Longitudinal diffusion MRI as surrogate outcome measure for myelopathy in adrenoleukodystrophy.

OBJECTIVE: To 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. METHODS: Clinical 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. RESULTS: Data 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. CONCLUSION: Although effect sizes were small, our prospective data illustrate the potential of dMRI as surrogate outcome measure for progression of myelopathy in men with adrenoleukodystrophy.