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Two structurally connected brain regions are more likely to interact, with the lengths of the structural bundles, their widths, myelination, and the topology of the structural connectome influencing the timing of the interactions. We introduce an in vivo approach for measuring functional delays across the whole brain in humans (of either sex) using magneto/electroence-phalography (MEG/EEG) and integrating them with the structural bundles. The resulting topochronic map of the functional delays/velocities shows that larger bundles have faster velocities. We estimated the topochronic map in multiple sclerosis patients, who have damaged myelin sheaths, and controls, demonstrating greater delays in patients across the network and that structurally lesioned tracts were slowed down more than unaffected ones. We provide a novel framework for estimating functional transmission delays in vivo at the single-subject and single-tract level. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcomes (PROs) may help patients and clinicians in selecting disease-modifying therapies (DMTs) for multiple sclerosis (MS). Objective: To evaluate PRO differences among first-line DMTs for relapsing-remitting (RR) people with MS (pwMS). Methods: Multicenter study. RR pwMS on first-line DMTs completed Fatigue Severity Scale (FSS), PROs Indices for MS (PRIMUS), 36-item Short-Form Health Survey (SF-36), treatment satisfaction questionnaire for medication (TSQM), Beck Depression Inventory-II (BDI-II), and Symbol Digit Modalities Test (SDMT). Differences among PROs across DMTs were tested by ANOVA. Multivariable linear regressions were used to investigate associations between PROs and the treatment group. Results: Two-hundred eighty pwMS were enrolled: 56% were on interferons (INF), 22% on dimethylfumarate (DMF), 13% on glatiramer acetate, and 9% on teriflunomide (Teri). Compared with INF, pwMS on Teri were the oldest, with higher disability, worst depression at BDI, worst cognitive performances at SDMT (p = 0.001), fatigue at FSS (p = 0.001), and activity limitation and quality of life respectively at PRIMUS (p = 0.005) and SF-36 Mental Composite Score (p < 0.001); pwMS on DMF reported highest side effects and, together with pwMS on Teri, better treatment satisfaction at TSQM. Conclusions: Compared with INF-treated patients, pwMS on DMF and Teri reported the best treatment satisfaction, although DMF-treated pwMS reported higher side effects and those on Teri the worst QoL and fatigue; however, the older age, higher disability and depression, and worse cognitive performance of pwMS on Teri suggest to be careful in evaluating these results. [ABSTRACT FROM AUTHOR]

Background: Little is known about the influence of multiple sclerosis (MS) diagnosis on parenthood attitude in people with MS (pwMS).Objective: To investigate the impact of diagnosis, clinical features and external disease-related influences on parenthood decision-making in Italian pwMS.Methods: A web-based survey was posted on SMsocialnetwork.com to investigate clinical status, parenthood desire, influences on family planning, pregnancy outcomes, abortions and adoptions of pwMS.Results: 33/395 respondents never wanted to become parent because of MS ("anti-parenthood after diagnosis"). 362 declared to be in favor of parenthood. 51% pwMS having a child by the survey time had already received the MS diagnosis at first childbirth. The frequency of a second child in pwMS after diagnosis was 38% compared to 67% in people without yet MS diagnosis. 16% of pwMS were discouraged to become parent after diagnosis, mainly by medical personnel. In 71% of respondents, diagnosis did not delay the decision to become parent and only 39% were counseled by treating physician to plan pregnancy. Patients' distribution according to the clinical phenotype (exclusively relapsing vs exclusively progressive) showed a higher proportion of progressive patients in the "anti-parenthood after diagnosis" subgroup.Conclusion: MS diagnosis impacted dramatically on the life project of 7% of pwMS that decided not to have children because of the disease and in pro-parenthood pwMS impacted especially on having the second child. Only a minority was counseled to plan pregnancy. A worse disease course driving to a progressive phenotype at survey time might have negatively impacted on parenthood desire. [ABSTRACT FROM AUTHOR]

Many guidelines are available for the management of lower urinary tract symptoms (LUTSs) in multiple sclerosis (MS) patients, but no agreement exists on the best approach for subjects without LUTSs. The objective of this study was to evaluate whether LUTSs can be detected in MS patients asymptomatic for urinary dysfunction, comparing three different tools [measure of post-void residual volume (PRV), bladder diary (BD), a focused questionnaire (IPSS)], and whether disability, disease duration and signs of pyramidal involvement are linked to their subclinical presence. 178 MS patients (118 women) have been included (mean age 41.2 years, mean disease duration 11.3 years, mean EDSS 2.2), and tested with the above-mentioned tools. PRV was abnormal in 14 subjects (7.8%), associated to abnormal findings at IPSS in 3 cases, at BD in 2 cases, at both in 1. BD was abnormal in 37 subjects (20.8%), with concomitant abnormal PRV in 2, abnormal IPSS in 10 cases, abnormal IPSS and BD in 1. IPSS was ≥ 9 in 43 subjects (24.1%). At least one test was abnormal in 76 patients (42.7%): 1 in 57 patients (32.0%), 2 in 17 (9.5%), and 3 tests in 2 (1.1%). Patients with at least one abnormal urinary variable, compared to patients without urinary abnormalities, had a more frequent pyramidal involvement (69.5 vs. 16.8%, χ(2) = 48.6, p < 0.00001), a more frequent occurrence of EDSS ≥2 (83.1 vs. 23.5%, χ(2) = 56.9, p < 0.00001), and a longer disease duration (15.7 ± 7.3 vs. 9.1 ± 7.1, t = 5.7, p < 0.00001). Asymptomatic LUTS were frequent but none of the tests used permitted to better identify asymptomatic patients. [ABSTRACT FROM AUTHOR]

To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT ( p < 0.01), PASAT 3″ ( p < 0.00), PASAT 2″ ( p < 0.03), SRT-D ( p < 0.02), and 10/36 SPART-D ( p < 0.04); as well as a significant increase of the FC of the DMN in the posterior cingulate cortex (PCC) and bilateral inferior parietal cortex (IPC). After cCR, a significant negative correlation between Stroop Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve. [ABSTRACT FROM AUTHOR]

We describe the clinical and neuropathological findings of three unrelated autopsy cases of MELAS harboring the A3243G transition in the mitochondrial DNA (mtDNA). Using immunohistochemical techniques, we studied the expression of several subunits of the respiratory chain in various brain regions from the same cases. In all three cases there was a reduced immunocytochemical staining for mtDNA-encoded subunits of the respiratory chain, confirming the presence of a defective mitochondrial protein synthesis in this disease. Mitochondrial abnormalities were mostly confined to multiple areas of different size and shape, in agreement with the focal character of the brain pathology in MELAS, and were most prominent in the cerebral cortex, providing a morphological contribution to the explanation of the cognitive regression of the patients. Immunoreactivity for mtDNA-encoded subunits was reduced in the walls of many pial and intracerebral arterioles of different brain regions but there was no clear correlation between territories of affected vessels and distribution of the histological and immunohistochemical lesions. Cerebral focal lesions in MELAS might have a metabolic nature and several pathogenetic mechanisms might be involved in the genesis of stroke-like episodes when there is a local increased ATP demand. [ABSTRACT FROM AUTHOR]