Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS

ObjectiveTo investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity.MethodsIn this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL and T1/T2 lesion volumes (T1LV/T2LV) were assessed between 84 patients with P-MS and 36 sex- and age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity in the previous 12 monthsResultspRNFL and GCIPL thickness were significantly lower in patients with P-MS than in HCs (p = 0.003 and p < 0.0001, respectively). INL was significantly thicker in patients aged < 51 years compared to the older ones and HCs (38.2 vs 36.5 and 36.7 m; p = 0.038 and p = 0.04, respectively) and in those who presented MRI activity (new T2/gadolinium-enhancing lesions) in the previous 12 months compared to the ones who did not and HCs (39.5 vs 36.4 and 36.7 m; p = 0.003 and p = 0.008, respectively). Recent MRI activity was significantly predicted by greater INL thickness (Nagelkerke R2 0.36, p = 0.001).ConclusionsINL thickness was higher in younger patients with P-MS with recent MRI activity, a criterion used in previous studies to identify a specific subset of patients with P-MS who best responded to disease-modifying treatment. If this finding is confirmed, we suggest that INL thickness might be a useful tool in stratification of patients with P-MS for current and experimental treatment choic

Mapping tissue microstructure across the human brain on a clinical scanner with soma and neurite density image metrics

Soma and neurite density image (SANDI) is an advanced diffusion magnetic resonance imaging biophysical signal model devised to probe in vivo microstructural information in the gray matter (GM). This model requires acquisitions that include b values that are at least six times higher than those used in clinical practice. Such high b values are required to disentangle the signal contribution of water diffusing in soma from that diffusing in neurites and extracellular space, while keeping the diffusion time as short as possible to minimize potential bias due to water exchange. These requirements have limited the use of SANDI only to preclinical or cutting‐edge human scanners. Here, we investigate the potential impact of neglecting water exchange in the SANDI model and present a 10‐min acquisition protocol that enables to characterize both GM and white matter (WM) on 3 T scanners. We implemented analytical simulations to (i) evaluate the stability of the fitting of SANDI parameters when diminishing the number of shells; (ii) estimate the bias due to potential exchange between neurites and extracellular space in such reduced acquisition scheme, comparing it with the bias due to experimental noise. Then, we demonstrated the feasibility and assessed the repeatability and reproducibility of our approach by computing microstructural metrics of SANDI with AMICO toolbox and other state‐of‐the‐art models on five healthy subjects. Finally, we applied our protocol to five multiple sclerosis patients. Results suggest that SANDI is a practical method to characterize WM and GM tissues in vivo on performant clinical scanners

Different MRI patterns in MS worsening after stopping fingolimod

Objective To analyze MRI images in patients with MS who experienced worsening of neurologic status (WNS) after stopping fingolimod (FTY).MethodsIn this retrospective study, demographic, clinical, and radiologic data of patients with MS who experienced WNS after stopping FTY were retrospectively collected. We introduced the "\u3b4Expanded Disability Status Scale (EDSS)-ratio" to identify patients who, after FTY withdrawal, showed an inflammatory flare-up exceeding the highest lifetime disease activity level. Patients with \u3b4EDSS-ratio > 1 were enrolled in the study.ResultsEight patients were identified. The mean (SD) age of the 8 (7 female) patients was 35.3 (4.9) years. The mean FTY treatment duration was 3.1 (0.8) years. The mean FTY discontinuation-WNS interval was 4 (0.9) months. The 4 patients with \u3b4EDSS-ratio 65 2 developed severe monophasic WNS (EDSS score above 8.5), characterized by clinical features and MRI findings not typical of MS, which we classified as "tumefactive demyelination pattern" (TDL) and "Punctuated pattern" (PL). Conversely, patients whose \u3b4EDSS-ratio was between 1 and 2 had clinical features and brain MRI compatible with a more typical, even if aggressive, MS relapse. In patients with TDL and PL, the flare-up of inflammatory activity led to severe tissue damage resulting in T2 but also T1 lesion volume increase at 6-month follow-up.ConclusionsPeculiar MRI features (TDL and PL), different from a typical MS flare-up, might occur in some patients who experienced WNS after stopping FTY. Further studies, also involving immunologic biomarkers, are necessary to investigate TDL or PL pathophysiology