The Physiological Variation of the Retinal Nerve Fiber Layer Thickness and Macular Volume in Humans as Assessed by Spectral Domain-Optical Coherence Tomography

Purpose.: With the introduction of spectral domain–optical coherence tomography (SD-OCT), changes in retinal nerve fiber layer (RNFL) thickness and macular volume (MV) can be detected with high precision. The aim of this study was to determine whether there is a physiological quantifiable degree of variation of these structures in humans. Methods.: This study took place during a 10-km charity run at VU University Medical Center Amsterdam. Weight, height, hydration status, RNFL thickness (ring scan, 12° around the optic nerve head), and MV (20° × 20°) were assessed in 69 subjects (44 runners, 25 controls) using SD-OCT with eye-tracking function. The SD-OCT scans were assessed before running (normal status), after running (more dehydrated status), and 1 to 1.5 hours after finishing the run (rehydrated status). Controls were measured at the same time intervals as the runners but did not participate in the running event. Changes over time were assessed by general linear models, correcting for repeated measurements. Results.: In runners, a significant increase in both RNFL thickness (94.4 μm [baseline] to 95.2 μm [rehydration], P = 0.04) and MV (288.9 μm [baseline] to 291.0 μm [rehydration], P < 0.001) over time was observed. Controls did not show significant changes over time. Anatomically, the physiological change of RNFL thickness was most marked in the nasal sectors. Conclusions.: This prospective study demonstrated a significant physiological variation of the RNFL thickness and MV at a proportion that, on an individual patient level, may be relevant for longitudinal studies in neurodegenerative diseases

Feasibility of detecting atrophy relevant for disability and cognition in multiple sclerosis using 3D-FLAIR

BACKGROUND AND OBJECTIVES: Disability and cognitive impairment are known to be related to brain atrophy in multiple sclerosis (MS), but 3D-T1 imaging required for brain volumetrics is often unavailable in clinical protocols, unlike 3D-FLAIR. Here our aim was to investigate whether brain volumes derived from 3D-FLAIR images result in similar associations with disability and cognition in MS as do those derived from 3D-T1 images. METHODS: 3T-MRI scans of 329 MS patients and 76 healthy controls were included in this cross-sectional study. Brain volumes were derived using FreeSurfer on 3D-T1 and compared with brain volumes derived with SynthSeg and SAMSEG on 3D-FLAIR. Relative agreement was evaluated by calculating the intraclass correlation coefficient (ICC) of the 3D-T1 and 3D-FLAIR volumes. Consistency of relations with disability and average cognition was assessed using linear regression, while correcting for age and sex. The findings were corroborated in an independent validation cohort of 125 MS patients. RESULTS: The ICC between volume measured with FreeSurfer and those measured on 3D-FLAIR for brain, ventricle, cortex, total deep gray matter and thalamus was above 0.74 for SAMSEG and above 0.91 for SynthSeg. Worse disability and lower average cognition were similarly associated with brain (adj. R2 = 0.24-0.27, p < 0.01; adj. R2 = 0.26-0.29, p < 0.001) ventricle (adj. R2 = 0.27-0.28, p < 0.001; adj. R2 = 0.19-0.20, p < 0.001) and deep gray matter volumes (adj. R2 = 0.24-0.28, p < 0.001; adj. R2 = 0.27-0.28, p < 0.001) determined with all methods, except for cortical volumes derived from 3D-FLAIR. DISCUSSION: In this cross-sectional study, brain volumes derived from 3D-FLAIR and 3D-T1 show similar relationships to disability and cognitive dysfunction in MS, highlighting the potential of these techniques in clinical datasets

Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome: A MAGNIMS Study

BACKGROUND AND OBJECTIVES: To compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing MS diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: CSF examination, brain and spinal cord MRI obtained ≤5 months from CIS onset, and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 CIS patients from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Score (EDSS) ≥ 3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), time (DIT) (including oligoclonal bands assessment) and DIS + DIT for predicting a second clinical attack (clinically definite [CD] MS) and EDSS ≥ 3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated. RESULTS: At follow-up (median = 69.1 months), 406/785 CIS patients developed CDMS. At 36 months, the 2017 DIS + DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60) and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision = 3.2; 2010 revision = 13.0; CDMS = 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥ 3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years. DISCUSSION: The 2017 McDonald criteria showed higher sensitivity, lower specificity and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria

The association between age and inflammatory disease activity on MRI in relapse-onset multiple sclerosis during long-term follow-up

BACKGROUND: Inflammatory disease activity in multiple sclerosis (MS) decreases with advancing age. Previous work found a decrease in contrast enhancing lesions (CELs) with age. Here we describe the relation of age and MRI measures of inflammatory disease activity during long-term follow-up in a large real-world cohort of people with relapse-onset MS. METHODS: We investigated MRI data from the long-term observational Amsterdam MS cohort. We used logistic regression models and negative binomial generalized estimating equations to investigate the associations between age and radiological disease activity after a first clinical event. RESULTS: We included 1,063 participants, and 10,651 cranial MRIs. Median follow-up time was 6.1 years (IQR 2.4-10.9 years). Older participants had a significantly lower risk of CELs on baseline MRI (40-50 years vs. 50 years vs. 50 years vs. 50 years, a less aggressive treatment strategy might be appropriate compared to younger patients