Using quantitative magnetic resonance imaging to track cerebral alterations in multiple sclerosis brain: A longitudinal study.

INTRODUCTION: Quantitative MRI quantifies tissue microstructural properties and supports the characterization of cerebral tissue damages. With an MPM protocol, 4 parameter maps are constructed: MTsat, PD, R1 and R2*, reflecting tissue physical properties associated with iron and myelin contents. Thus, qMRI is a good candidate for in vivo monitoring of cerebral damage and repair mechanisms related to MS. Here, we used qMRI to investigate the longitudinal microstructural changes in MS brain. METHODS: Seventeen MS patients (age 25-65, 11 RRMS) were scanned on a 3T MRI, in two sessions separated with a median of 30 months, and the parameters evolution was evaluated within several tissue classes: NAWM, NACGM and NADGM, as well as focal WM lesions. An individual annual rate of change for each qMRI parameter was computed, and its correlation to clinical status was evaluated. For WM plaques, three areas were defined, and a GLMM tested the effect of area, time points, and their interaction on each median qMRI parameter value. RESULTS: Patients with a better clinical evolution, that is, clinically stable or improving state, showed positive annual rate of change in MTsat and R2* within NAWM and NACGM, suggesting repair mechanisms in terms of increased myelin content and/or axonal density as well as edema/inflammation resorption. When examining WM lesions, qMRI parameters within surrounding NAWM showed microstructural modifications, even before any focal lesion is visible on conventional FLAIR MRI. CONCLUSION: The results illustrate the benefit of multiple qMRI data in monitoring subtle changes within normal appearing brain tissues and plaque dynamics in relation with tissue repair or disease progression.

Comparative study of AQP4-NMOSD, MOGAD and seronegative NMOSD: a single-center Belgian cohort.

PURPOSE: To emphasize physio-pathological, clinical and prognosis differences between conditions causing serious and sometimes very similar clinical manifestations: anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies related diseases, and seronegative NMOSD (neuromyelitis optica spectrum disorders). METHODS: Based on Wingerchuk et al. (Neurology 85:177-189, 2015) criteria for NMOSD and on those more recently proposed by Jarius et al. (J Neuroinflammation 15:134, 2018) for MOGAD (MOG associated disorders), we retrospectively surveyed 10 AQP4-NMOSD, 8 MOGAD and 2 seronegative NMOSD, followed at the specialized neuroimmunology unit of the CHU Liège. RESULTS: Female predominance was only observed in AQP4 group. Age at onset was 37.8 and 27.7 years old for AQP4-NMOSD and MOGAD respectively. In both groups, the first clinical event most often consisted of optic neuritis (ON), followed by isolated myelitis. Fifteen of our 20 patients encountered a relapsing course with 90% relapses in AQP4-NMOSD, 62.5% in MOGAD and 50% in seronegative group, and a mean period between first and second clinical event of 7.1 and 4.8 months for AQP4-NMOSD and MOGAD, respectively. In total we counted 54 ON, with more ON per patient in MOGAD. MOG-associated ON mainly affected the anterior part of the optic nerve with a papilledema in 79.2% of cases. Despite a fairly good visual outcome after MOG-associated ON, retinal nerve fibre layer (RNFL) thickness decreased, suggesting a fragility of the optic nerve toward further attacks. CONCLUSION: As observed in larger cohorts, our MOGAD and AQP4-NMOSD cases differ by clinical and prognostic features. A better understanding of these diseases should encourage prompt biological screening and hasten proper diagnosis and treatment.

Atezolizumab Treatment for Progressive Multifocal Leukoencephalopathy.

Atezolizumab successfully reinvigorated JC virus immunity in a patient in Belgium with progressive multifocal leukoencephalopathy, as demonstrated by clinical, virologic, and radiologic response to treatment. However, the treatment also resulted in immune reconstitution inflammatory syndrome and life-threatening immune-related adverse events. These conditions were treated with corticosteroids, leading to treatment resistance.

The frequency and influence of dementia risk factors in prodromal Alzheimer's disease.

We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.