To evaluate cognitive changes in a cohort of radiologically isolated syndromes (RIS) suggestive of multiple sclerosis (MS) and to assess their relationship with quantitative magnetic resonance (MR) ...measures such as white matter (WM), lesion loads, and cerebral atrophy.
We assessed the cognitive performance in a group of 29 subjects with RIS recruited from 5 Italian MS centers and in a group of 26 patients with relapsing-remitting MS (RRMS). A subgroup of 19 subjects with RIS, 26 patients with RRMS, and 21 healthy control (HC) subjects also underwent quantitative MR assessments, which included WM T1 and T2 lesion volumes and global and cortical brain volumes.
Cognitive impairment of the same profile as that of RRMS was found in 27.6% of our subjects with RIS. On MR scans, we found comparable levels of lesion loads and brain atrophy in subjects with RIS and well-established RRMS. In subjects with RIS, high T1 lesion volume (ρ = 0.526, p = 0.025) and low cortical volume (ρ = -0.481, p = 0.043) were associated with worse cognitive performance.
These findings emphasize the importance of including accurate neuropsychological testing and quantitative MR metrics in subjects with RIS suggestive of MS. They can provide a better characterization of these asymptomatic subjects, potentially useful for diagnostic and therapeutic decisions.
Cognitive dysfunction involves 40–65% of multiple sclerosis patients and can have a great functional impact. It can be detected in all the disease phenotypes since the early stages of the disease, ...and tends to progress over time. Memory, complex attention, information-processing speed and executive functions are most commonly involved. The relationship between cognitive changes and magnetic resonance imaging (MRI) findings may involve changes in different areas, including white matter lesions, cortical and deep grey matter and normal appearing brain tissue on conventional MRI. The search for effective therapeutic strategies is a major undertaking, involving the use of both pharmacologic and rehabilitative approaches. Early treatment with disease-modifying drugs that can contain the disease burden in the brain seems to be highly advisable in order to prevent or delay the development of cognitive impairment.
Background:
There is controversial information on the efficacy of cognitive rehabilitation in multiple sclerosis (MS).
Objective:
The objective of this paper is to test a home-based computerized ...program for retraining attention dysfunction in MS.
Methods:
Relapsing–remitting patients who failed > 2 tests of attention on an extensive neuropsychological battery were randomized to specific or nonspecific computerized training (ST, n-ST), in one-hour sessions, twice a week for three months. Outcome measures included neuropsychological assessment, depression, fatigue, everyday activities and a visual analogue scale assessing attentive performance (VAS). Assessments were repeated after the interventions and after a further three months. Statistical analysis included the analysis of variance (ANOVA) for repeated measures.
Results:
Eighty-eight out of 102 randomized patients completed the study (69 women, age 40.9 ± 11.5 years, disease duration 13.0 ± 8.7 years, Expanded Disability Status Scale score 2.7 ± 1.5). Fifty-five patients were randomized to ST, 33 to n-ST. A benefit of the ST was observed on the Paced Auditory Serial Addition Test (p < 0.002). However, patient self-report did not reveal differences between ST and n-ST patient groups.
Conclusion:
Although our program trained different attention components, we could detect some improvements exclusively on tasks of sustained attention. Moreover, patient self-perceived results may be independent of the training program.
Abstract Background Caregivers’ involvement in the diagnostic and monitoring processes of the level of consciousness of patients with Disorders of Consciousness (DoC) is strongly encouraged by ...international guidelines, as current literature suggests a better chance to detect behavioural responses when caregivers are involved in clinical assessments. Since caregivers’ involvement during clinical assessments can be difficult, the Social And Family Evaluation (SAFE) scale has been recently proposed as a standardised tool that caregivers can autonomously use to collect their opinions about the level of consciousness of patients with DoC, based on the behaviours manifested by the patients in a given time-window. Objective Providing preliminary results concerning SAFE adoption. Methods 22 patients with DoC were assessed through the Coma Recovery Scale-revised (CRS-r), while their caregivers filled-in the SAFE. Results The SAFE showed a very high internal consistency, very high test-retest reliability, and high criterion validity when correlated to the CRS-r total score. Moreover, in line with the literature, the SAFE allowed the detection of some behaviours indicative of a higher level of consciousness than those detected by clinicians through the CRS-r in more than half of the sample. Conclusion Overall, these preliminary data are promising for the adoption of the SAFE to collect the opinions of the caregivers about the level of consciousness of patients with DoC, especially in those settings where it would be otherwise difficult to monitor the patients, such as long-term care structures and at home, as a tool for telemedicine allowing the monitoring of patients in remote settings.
To assess relapses, disability progression and the role of disease modifying drugs (DMDs) in the year after delivery in women with multiple sclerosis (MS).
We prospectively followed-up pregnancies ...occurring between 2002 and 2008 in women with MS, recruited from 21 Italian MS centres. The risk of relapses and disability progression in the year after delivery was assessed using time-dependent Cox regression analysis.
350 out of 423 pregnancies were assessed (pregnancies not resulting in live birth and with a postpartum follow-up period shorter than 1 year were excluded from the analysis). 148 patients (42.3%) had at least one relapse in the year after delivery. An Expanded Disability Status Scale (EDSS) score at conception ≥2.0 (HR=1.4; 95% CI 1.1 to 2.0; p=0.046) and a higher number of relapses before (HR=1.5; 95% CI 1.2 to 1.8; p<0.001) and during pregnancy (HR=2.3; 95% CI 1.6 to 3.4; p<0.001) were related to a higher risk of postpartum relapses. On the contrary, early DMD resumption after delivery marginally reduced the risk of postpartum relapses (HR=0.7, 95% CI 0.4 to 1.0; p=0.079). Moreover, 44/338 women progressed by at least one point on the EDSS. Disability progression was associated with a higher number of relapses before (HR=1.4, 95% CI 1.1 to 1.9; p=0.047) and after delivery (HR=2.7, 95% CI 1.4 to 5.2; p=0.002).
Our findings show an increased risk of postpartum relapses and disability accrual in women with higher disease activity before and during pregnancy. Since it may reduce the risk of postpartum relapses, early DMD resumption should be encouraged, particularly in patients with more active disease.
To assess the relationship between breastfeeding and risk of puerperal relapses in a large cohort of patients with multiple sclerosis (MS).
We prospectively followed-up pregnancies occurring between ...2002 and 2008 in women with MS, recruited from 21 Italian MS centers, and gathered data on breastfeeding through a standardized interview. The risk of relapses after delivery was assessed using the Cox regression analysis.
A total of 302 out of 423 pregnancies in 298 women resulted in full-term deliveries. Patients were followed up for at least 1 year after delivery. The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not. In the multivariate analysis, adjusting for age at onset, age at pregnancy, disease duration, disability level, and relapses in the year prior to pregnancy and during pregnancy, treatment with disease-modifying drugs (DMDs), and exposure to toxics, the only significant predictors of postpartum relapses were relapses in the year before pregnancy (hazard ratio HR = 1.5; 95%confidence interval CI 1.3-1.9; p < 0.001) and during pregnancy (HR = 2.2; 95% CI 1.5-3.3; p < 0.001).
In our sample, postpartum relapses were predicted only by relapses before and during pregnancy. Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity. Our results can assist neurologists facing the breastfeeding issue in mother counseling and shared decision-making. Especially, among patients with high risk of postpartum relapses, breastfeeding may not be feasible and early postpartum treatment should be an option.
To assess the presence of cortical lesions (CLs) as detected by MRI in subjects with radiologically isolated syndrome (RIS).
Fifteen subjects with RIS underwent an MRI examination, including a double ...inversion recovery sequence for CL assessment. T2-hyperintense white matter (WM) lesion volume (LV) and normalized volumes of brain and cortex were also obtained.
Thirty-four CLs were identified in 6 of 15 (40%) subjects with RIS and predominantly distributed in frontotemporal lobes. CLs were frequent in subjects with RIS with immunoglobulin G oligoclonal bands on CSF, cervical cord lesions, and dissemination in time on brain MRI. WM LV was higher in subjects with CLs than in those without CLs (11.5 ± 10.1 vs 3.9 ± 2.8 cm(3), p = 0.04). Indeed, CL number and volume correlated with WM LV (r = 0.57, p = 0.03 and r = 0.61, p = 0.01). All subjects with CLs were classified in a previous study as having a very high probability of having relapsing-remitting multiple sclerosis (MS) on a logistic regression analysis of quantitative MRI indices.
We found CLs in subjects with RIS, a condition characterized by the unanticipated MRI finding of WM lesions highly suggestive of MS in the absence of a clinical scenario. CLs were mainly localized to the frontotemporal lobes and were associated with important markers of evolution to MS.
To assess pregnancy and fetal outcomes after in utero exposure to interferon-β (IFNβ) in all pregnancies occurring in women with multiple sclerosis (MS) during the study period, with a specific focus ...on the risk of spontaneous abortion.
In this cohort study, data were gathered through a standardized, semi-structured interview. Patients who discontinued IFNβ less than 4 weeks from conception (exposed) were compared with those who had discontinued the drug at least 4 weeks from conception or who were never treated (not exposed). Possible confounders were handled through multivariate analyses adjusted for propensity score (PS).
We collected data on 396 pregnancies in 388 women, 88 classified as exposed (mean exposure 4.6 ± 5.8 weeks). IFNβ exposure was not associated with an increased risk of spontaneous abortion (PS-adjusted odds ratio OR 1.08, 95% confidence interval CI 0.4 to 2.9, p = 0.88), although it was associated with both lower baby weight (PS-adjusted β -113.8, p < 0.0001) and length (PS-adjusted β -1.102, p < 0.0001). Proportion of spontaneous abortion in exposed patients fell within the range expected for the Italian population in the same period. IFNβ exposure (PS-adjusted OR 2.11, 95% CI 1.18 to 3.78, p = 0.012) and cesarean delivery were the only predictors of preterm delivery. In the exposed group, we did not observe any significant fetal complications, malformations, or developmental abnormalities over a median follow-up of 2.1 years.
Our findings point to the relative safety of IFNβ exposure times of up to 4 weeks and can assist neurologists facing therapeutic decisions in women with MS with a pregnancy plan.
The aim of this study was to investigate the impact of anxiety on the cognitive performance of a clinical sample of relapsing—remitting (RR) MS patients. One hundred ninety patients (140 females) ...were included in the study and assessed through the beck depression inventory, the state-trait anxiety inventory and the Rao’s brief repeatable battery which assesses cognitive domains most frequently impaired in MS. As for neuropsychological performance, a total of 76 (40 %) subjects fulfilled our criterion for cognitive impairment. Tests most frequently failed by cognitive impairment (CI) patients were those assessing complex attention and information processing speed Simbol Digit Modalities Test (SDMT), Paced Auditory Serial Auditory Test (PASAT) 3 and 2 and verbal memory. In the univariate analysis, state anxiety was related to failure on the SDMT (
p
= 0.042), and marginally, to failure on the PASAT-3 (
p
= 0.068), and to the presence of CI (
p
= 0.082). Moderate/severe depression was detected in 38 (20 %) patients and fatigue in 109 (57 %). Higher depression scores were related to impairment on the ST (OR = 1.05; 95 % CI 1.01–1.10;
p
= 0.029).
