The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis.

Choroid plexus (CP) can be seen as a watchtower of the central nervous system (CNS) that actively regulates CNS homeostasis. A growing body of literature suggests that CP alterations are involved in the pathogenesis of multiple sclerosis (MS) but the underlying mechanisms remain elusive. CPs are enlarged and inflamed in relapsing-remitting (RRMS) but also in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) stages, far beyond MS diagnosis. Increases in the choroid plexus/total intracranial volume (CP/TIV) ratio have been robustly associated with increased lesion load, higher translocator protein (TSPO) uptake in normal-appearing white matter (NAWM) and thalami, as well as with higher annual relapse rate and disability progression in highly active RRMS individuals, but not in progressive MS. The CP/TIV ratio has only slightly been correlated with magnetic resonance imaging (MRI) findings (cortical or whole brain atrophy) and clinical outcomes (EDSS score) in progressive MS. Therefore, we suggest that plexus volumetric assessments should be mainly applied to the early disease stages of MS, whereas it should be taken into consideration with caution in progressive MS. In this review, we attempt to clarify the pathological significance of the temporal CP volume (CPV) changes in MS and highlight the pitfalls and limitations of CP volumetric analysis.

Cognitive Fatigability is Independent of Subjective Cognitive Fatigue and Mood in Multiple Sclerosis.

BACKGROUND: Sustained cognitive testing is used to detect cognitive fatigability and is often considered a substitute for subjective cognitive fatigue (CF). However, the relationship between cognitive fatigability and subjective CF in people with multiple sclerosis (PwMS) remains undetermined. OBJECTIVE: To explore potential associations between fatigability induced by sustained cognitive testing and subjective CF in PwMS. METHODS: We gave 120 PwMS and 60 demographically matched, healthy individuals the Beck Depression Inventory-FastScreen (BDI-FS) to measure mood and the Modified Fatigue Impact Scale to measure CF. In addition, we used the Quotient ADHD Test, a sustained attention test, to measure cognitive fatigability. We also explored potential correlations between the individuals' performance on the sustained attention test and thalamic volume using recent MRI scans. RESULTS: Forty-one (34.2%) of the PwMS exhibited cognitive fatigability. These 41 were found to be significantly older (P=0.006), had been diagnosed with the disease for longer (P=0.03), had higher scores (P<0.001) on the Expanded Disability Status Scale, and had reduced thalamic volume (P=0.04) compared with the 79 (65.8%) PwMS not exhibiting cognitive fatigability. The PwMS exhibiting cognitive fatigability scored similarly on the BDI-FS (P=0.21) and self-reported similar rates of CF (P=0.62) as the PwMS not exhibiting cognitive fatigability. CONCLUSION: Cognitive fatigability induced by sustained cognitive testing is not an accurate clinical alternative to subjective CF. This study provides evidence to support cognitive fatigability and CF in PwMS as two distinct concepts.

Clinically reliable cognitive decline in relapsing remitting multiple sclerosis: Is it the tip of the iceberg?

OBJECTIVES: Cognitive impairment is common in multiple sclerosis, but the brain MRI correlates in relapsing remitting multiple sclerosis remain controversial. The current study aimed to investigate whether cognitive decline can be predicted by global and/or regional brain atrophy. METHODS: Sixty-three patients with relapsing remitting multiple sclerosis (36 men, mean age 39.9 ± 9.4 years old, mean EDSS 1.4 ± 1.2, mean disease duration 4.9 ± 4.3 years) and 46 healthy controls (21 men, mean age 37.5 ± 10.8 years old) were included. Demographic data were obtained, and a longitudinal neuropsychological and global and regional MRI brain volume assessment was performed. RESULTS: The patients performed worse than controls in most neuropsychological tests at baseline. The percentage of patients with clinically meaningful cognitive decline ranged from only 0% to 7.9%. Statistically significant volume reduction was found for all MRI measures except for the left accumbens nucleus. Whole or regional brain atrophy ranged from -0.02% to -0.25%, with subcortical structures showing the largest atrophy rates. A total of 22.2% to 93.7% patients showed atrophy across the brain structures assessed volumetrically. DISCUSSION: It was regional rather than whole-brain changes that significantly predicted cognitive decline for the patients in the tasks that tested processing speed, visuo-spatial and inhibition skills. The overall data suggest that the progression of cognitive impairment in relapsing remitting multiple sclerosis as captured by conventional neuropsychological testing is the tip of the iceberg of neurodegenerative sequelae in the disease. Also, regional volumetric changes are better than whole-brain atrophy at predicting cognitive dysfunction.

Brain volume dynamics in multiple sclerosis. A case-control study.

Objectives: In this study, we aimed to explore the extent and clinical relevance of brain volume dynamics in relapsing remitting multiple sclerosis (RRMS). Methods: Sixty-three patients with RRMS with a disease duration of about 5 years (36 women, mean age 39.9 ± 9.4 years; mean EDSS1.4 ± 1.2, mean relapse rate 0.98 ± 1.17) and 50 healthy control individuals (24 women, mean age 39.1 ± 10.2 years) were recruited and imaged on a MRI scanner by using post-gadolinium high-resolution3D T1W sequences. Cross-sectional and longitudinal volumetric data were obtained by using SIENA(X) and FIRST software. Results: Patients showed significantly lower subcortical volumes compared to healthy controls. Interestingly, the educational level predicted the rate of right thalamus atrophy. The mean annualized percentage of brain volume change (aPBVC) was -0.92% (±1.64%) and was presented in higher rates during the first five years after MS diagnosis. Conclusion: Brain atrophy mainly involved subcortical grey matter structures and was more conspicuous during the first years of MS diagnosis. The buffering role of education in atrophy was also corroborated by this study.

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by focal or diffuse inflammation, demyelination, axonal loss and neurodegeneration. Brain atrophy can be seen in the earliest stages of MS, progresses faster compared to healthy adults, and is a reliable predictor of future physical and cognitive disability. In addition, it is widely accepted to be a valid, sensitive and reproducible measure of neurodegeneration in MS. Reducing the rate of brain atrophy has only recently been incorporated as a critical endpoint into the clinical trials of new or emerging disease modifying drugs (DMDs) in MS. With the advent of easily accessible neuroimaging softwares along with the accumulating evidence, clinicians may be able to use brain atrophy measures in their everyday clinical practice to monitor disease course and response to DMDs. In this review, we will describe the different mechanisms contributing to brain atrophy, their clinical relevance on disease presentation and course and the effect of current or emergent DMDs on brain atrophy and neuroprotection.

Efficacy of computer-based cognitive training in neuropsychological performance of patients with multiple sclerosis: A systematic review and meta-analysis.

IMPORTANCE: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by relapses and a progressive course that may lead to accumulation of physical and cognitive disability. Cognitive training interventions seem to improve the cognitive performance of MS patients. The aim of the present meta-analysis is to quantitatively investigate the effect of computer-based cognitive rehabilitation on the neuropsychological performance of patients with MS. METHODS: We performed a systematic review of the PubMed database to identify available studies that performed computer-based cognitive training in MS patients. Studies should have reported pre- and post-cognitive training neuropsychological tests scores and included both intervention and placebo/no-intervention MS groups. We analyzed the effect of computer-based cognitive rehabilitation on individual neuropsychological tests, on specific functional domains, and on overall cognition performance. The effect-size of cognitive training pre- and post-treatment compared to placebo/ no-intervention was estimated using the standardized mean difference (SMD). The 95% confidence intervals (CI) were estimated using a Z test by comparing the final values. Baseline between-group differences in selected outcomes were estimated with ANOVA. RESULTS: In total, 9 studies fulfilled the criteria for inclusion and were inserted in the quantitative analysis. Computer-based cognitive training was found to improve the performance in the memory domain of MS patients compared to control interventions (SMD, 0.22; 95% CI 0.01-0.43; p = 0.04). Moreover, in the subgroup analysis, cognitive training demonstrated significant effects in Selective Reminding Test (SRT) delay memory (SMD, 0.58; 95% CI 0.29-0.87; p < 0.001). CONCLUSIONS: The present meta-analysis revealed a significant effect for computer-based cognitive training on the performance of the memory domain of patients with MS. This finding may have significant implications in the current treatment practice when cognitive decline is detected in MS patients.

Vitamin B12, folate, and homocysteine levels and multiple sclerosis: A meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating and disabling inflammatory disease of the central nervous system. Several factors contribute to MS pathogenesis including genetic-environmental interactions. Case-control studies suggest that there might be associations between MS and homocysteine (Hcy), vitamin B12, and folate blood levels. AIM: To meta-analyze all available data describing associations between MS and serum or plasma Hcy, vitamin B12, and folate levels. METHODS: The PubMed, MEDLINE, and EMBASE databases were searched for eligible case-control studies published until June 2017. After data extraction, separate analyses using mainly random-effects models were conducted to test for associations between MS and vitamin B12, Hcy, or folate blood levels. RESULTS: Twelve, 12, and 9 studies met the inclusion criteria for meta-analysis of MS and Hcy, vitamin B12, and folate levels, respectively. The standardized mean difference (SMD) between MS patients and controls was statistically significant for Hcy (SMD: 0.70, 95% CI: 0.06, 1.34). Stratification according to clinical pattern did not reveal significant differences between relapsing-remitting MS patients and controls (SMD: 0.30, 95% CI: -0.93, 1.54) or between secondary progressive MS patients and controls (SMD: 0.12, 95% CI: -1.65, 1.90). There were no significant differences in SMD between MS patients and healthy individuals for vitamin B12 (SMD: -0.09, 95% CI: -0.29, 0.10) or folate (SMD: -0.06, 95% CI: -0.17, 0.05). CONCLUSION: MS patients tend to have elevated Hcy blood levels compared to healthy controls. Hcy may contribute to the pathogenesis of the disease.

Faces Attract Infants' Attention in Complex Displays.

Infant's face preferences have previously been assessed in displays containing 1 or 2 faces. Here we present 6-month-old infants with a complex visual array containing faces among multiple visual objects. Despite the competing objects, infants direct their first saccade toward faces more frequently than expected by chance (Experiment 1). The attention-grabbing effect of faces is not selective to upright faces (Experiment 2) but does require the presence of internal facial elements, as faces whose interior has been phase-scrambled did not attract infants' attention (Experiment 3). On the contrary, when the number of fixations is considered, upright faces are scanned more extensively than both inverted and phase-scrambled faces. The difference in selectivity between the first look measure and the fixation count measure is discussed in light of a distinction between attention-grabbing and attention-holding mechanisms.