Multiparameter MRI quantification of microstructural brain alteration in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disorder of the central nervous system (CNS), which stands as the most common cause of neurological disability in young adults. Traditionally, MS is primarily characterized by the accumulation of focal demyelinated plaques within the white matter (WM). With the advent of highly developed histopathological techniques in the second half of the 20th century, it became clear that focal lesions are also present in grey matter (GM), and that neurodegeneration diffusely affects macroscopically normal-appearing brain tissues (NABT). These observations are particularly evident in the progressive forms of the disease. Nevertheless, in vivo evaluation of MS patients remains unsatisfactory, because conventional MRI is insensitive to many pathological mechanisms underpinning MS. In the present work, we precisely aimed at improving the impact of 3 Tesla MRI on the detection and characterization of these processes, using quantitative MRI (qMRI) parameters sensitive to iron and myelin contents: magnetization transfer (MT) saturation, effective transverse relaxation rate R2* (1/T2*) and longitudinal relaxation rate R1 (1/T1). We designed a prospective cross-sectional study, contrasting 36 MS patients to 36 age-matched healthy controls. Processing and statistical analyses of MRI data were conducted on the basis of two distinct approaches: general analysis looked for differences in qMRI parameters summarized over three different NABT classes (normal appearing cortical and deep grey matters, normal appearing white matter), whereas voxel-based analyses assessed the spatial distribution of qMRI changes within normal appearing cortical and deep grey matters. Consistent with histopathological findings, results suggest a widespread reduction in myelin and/or iron contents within NABT of MS patients, both at the global and loco-regional levels, and beyond the ability of atrophy measurements. Interestingly, these microstructural alterations tend to be more pronounced and diffuse in progressive MS population. Moreover, correlation analyses indicate that they might play a significant role in determining brain volume loss as well as irreversible disability in MS. Our cross-sectional study proves that simultaneous quantification of multiple MRI parameters can sensitively assess NABT microstructure in MS. However, future large-scale studies should evaluate the reproducibility and predictive values of these results

The Complex Interplay Between Trait Fatigue and Cognition in Multiple Sclerosis

peer reviewedCognitive impairments are frequent in patients with Multiple Sclerosis (MS). Yet, the influence of MS-related symptoms on cognitive status is not clear. Studies investigating the impact of trait fatigue along with anxio-depressive symptoms on cognition are seldom, and even less considered fatigue as multidimensional. Moreover, these studies provided conflicting results. Twenty-nine MS patients and 28 healthy controls, matched on age, gender and education underwent a full comprehensive neuropsychological assessment. Anxio-depressive and fatigue symptoms were assessed using the HAD scale and the MFIS, respectively. Six composite scores were derived from the neuropsychological assessment, reflecting the cognitive domains of working memory, verbal and visual learning, executive functions, attention and processing speed. Stepwise regression analyses were conducted in each group to investigate if trait cognitive and physical fatigue, depression and anxiety are relevant predictors of performance in each cognitive domain. In order to control for disease progression, patient’s EDSS score was also entered as predictor variable. In the MS group, trait physical fatigue was the only significant predictor of working memory score. Cognitive fatigue was a predictor for executive functioning performance and for processing speed (as well as EDSS score for processing speed). In the healthy controls group, only an association between executive functioning and depression was observed. Fatigue predicted cognition in MS patients only, beyond anxio-depressive symptoms and disease progression. Considering fatigue as a multidimensional symptom is paramount to better understand its association with cognition, as physical and cognitive fatigue are predictors of different cognitive processes

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

peer reviewedObjectives: 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 diagnostic criteria for NMOSD and 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 Liege. 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 the seronegative group, and a mean period between the 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 fiber 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

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

peer reviewedIntroduction: 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. Emilie Lommers and Christophe Phillips equally contributed to the work

Exploring the specificity of fatigue-related brain activity in early Multiple Sclerosis.

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Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.

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Motor Fatigue Measurement by Distance-Induced Slow Down of Walking Speed in Multiple Sclerosis

Background: Motor fatigue and ambulation impairment are prominent clinical features of people with multiple sclerosis (pMS). We hypothesized that a multimodal and comparative assessment of walking speed on short and long distance would allow a better delineation and quantification of gait fatigability in pMS. Objectives: To compare 4 walking paradigms: the timed 25-foot walk (T25FW), a corrected version of the T25FW with dynamic start (T25FW+), the timed 100-meter walk (T100MW) and the timed 500-meter walk (T500MW). Methods: Thirty controls and 81 pMS performed the 4 walking tests in a single study visit. Results: The 4 walking tests were performed with a slower WS in pMS compared to controls even in subgroups with minimal disability. The finishing speed of the last 100-meter of the T500MW was the slowest measurable WS whereas the T25FW+ provided the fastest measurable WS. The ratio between such slowest and fastest WS (Deceleration Index, DI) was significantly lower only in pMS with EDSS 4.0-6.0, a pyramidal or cerebellar functional system score reaching 3 or a maximum reported walking distance !4000m. Conclusion: The motor fatigue which triggers gait deceleration over a sustained effort in pMS can be measured by the WS ratio between performances on a very short distance and the finishing pace on a longer more demanding task. The absolute walking speed is abnormal early in MS whatever the distance of effort when patients are unaware of ambulation impairment. In contrast, the DI-measured ambulation fatigability appears to take place later in the disease course