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.
To assess the evolution of cognitive and psychosocial functioning in a cohort of childhood and juvenile multiple sclerosis (MS) cases after a mean period of 2 years had elapsed since baseline ...evaluation.
In this cohort study, we used the same extensive neuropsychological battery with alternative versions of the tests assessing memory, attention/concentration, executive functions, and language. Fatigue and depression were also measured. An interview on school and daily living activities was obtained from the parents. The cognitive performance of the patients was compared with that of demographically matched healthy controls (HC).
Fifty-six patients and 50 HC were assessed. At follow-up, criteria for cognitive impairment (failure on at least 3 tests) were fulfilled in 39 patients (70%) and 75% of the cases were classified as having a deteriorating cognitive performance. Changes were prominent in tests of verbal memory, complex attention, verbal fluency, and receptive language. In the regression analysis, the only significant predictor of cognitive deterioration was older age of the subject (odds ratio 1.9, 95% confidence interval 1.2-2.9, p = 0.003). Psychiatric disorders, most frequently depression, were diagnosed in 12 patients (30.5%). Fatigue was reported by 21% of the patients. MS negatively affected school and everyday activities in 30% to 40% of the subjects.
Our findings confirm the importance of systematic assessment of cognitive and psychosocial issues in children and teens with MS. The progressive nature of the cognitive difficulties emphasizes the need for developing effective treatment strategies.
The Brief Repeatable Battery of Neuropsychological Tests (BRB) is by far the most widely used instrument to estimate cognitive dysfunction in multiple sclerosis (MS) patients. However, the paucity of ...normative data currently limits its applicability. We administered the BRB to 200 healthy subjects to obtain normative values. Moreover, we assessed the influence of demographic factors on the test scores and calculated corrections for these relevant factors. To test executive functions not explored by the BRB, we also included the Stroop word-color task (ST). Higher educational level was associated with better performance on all the tests, except for the world list generation (WLG) and the ST, considering version A, and on Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT) and Selective Reminding Test-Delayed (SRT-D), considering version B. Females performed better than males on the WLG considering version A, and on the SRT-Long Term Storage (SRT-LTS) and SRT-Consistent Long Term Retrieval (SRT-CLTR) considering version B. Increasing age was associated with worse performance on the ST in version A, and on the SRT-LTS, SRT-CLTR and WLG in version B. Our data can improve the applicability of the BRB for both clinical and research purposes.
To assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting (RR) multiple sclerosis (MS).
Conventional MR was acquired in 41 patients with RR MS and 16 ...demographically matched normal control subjects (NCs). An automated analysis tool was used with conventional T1-weighted MRI to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed using the Rao Brief Repeatable Battery. Relationship between volumetric MR measures and neuropsychological scores was assessed.
Neuropsychological assessment allowed for the identification of 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. The whole MS sample showed lower values of normalized cortical volumes (NCVs) than did the NC group (p = 0.01). Upon grouping of MS patients according to cognitive performance, NCV values were lower (p = 0.02) in MS-ci patients than in both MS-cp patients and NCs. Moreover, there were positive correlations between NCV values and measures of verbal memory (r = 0.51, p = 0.02), verbal fluency (r = 0.51, p = 0.01), and attention/concentration (r = 0.65, p < 0.001) in MS-ci patients. Furthermore, NCV values were decreased in patients who scored lower on a greater number of tests (r = -0.58, p < 0.01) in the MS-ci group. None of the neuropsychological measures correlated to NCV values in the MS-cp patient group.
Cortical atrophy was found only in cognitively impaired patients and was significantly correlated with a poorer performance on tests of verbal memory, attention/concentration, and verbal fluency. Gray matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.
To assess the impact of multiple sclerosis (MS) on cognitive and psychosocial functioning in childhood and juvenile cases.
We used an extensive neuropsychological battery assessing IQ, memory, ...attention/concentration, executive functions, and language. Fatigue and depression were also measured. An interview on school and daily living activities was obtained from the parents. Performance of cases was compared with that of demographically matched healthy controls.
Sixty-three patients and 57 healthy controls were assessed. Five patients (8%) exhibited a particularly low IQ (<70). Criteria for cognitive impairment (failure on at least three tests) were fulfilled in 19 patients (31%), whereas 32 patients (53%) failed at least two tests. Beyond deficits in memory, complex attention, and executive functions, the profile of deficits was characterized by involvement of linguistic abilities. In the regression analysis, the only significant predictor of cognitive impairment was an IQ score lower than 90 (odds ratio OR 18.2, 95% CI 4.6-71.7, p < 0.001). Considering the IQ score as a dependent variable, the only significant predictor was represented by younger age at onset (OR 0.7, 95% CI 0.5-0.9, p = 0.009). Depressive symptoms were reported by 6% of the cases, and fatigue was reported by 73% of the cases. MS negatively affected school and everyday activities in 56% of the subjects.
In childhood and juvenile cases, multiple sclerosis (MS) is associated with cognitive impairment and low IQ scores, the latter related to younger age at onset. These aspects are of critical importance in helping children and adolescents with MS to manage their difficulties and psychosocial challenges.
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system typically affecting young adults. Psychological coping has proved to be crucially important for adjusting to ...the adaptive demands of chronic diseases, and in the last few years it has received growing interest in MS. A common finding in the literature is that MS patients tend to adopt dysfunctional avoiding strategies and to rely less on task-oriented and positive attitude strategies, which represent a better adjustment to disease-related challenges. Moreover, the studies show higher psychoticism in MS subjects compared with the general population, and higher levels of depression and anxiety that can contribute to lower QoL perception. In our study including 63 MS patients cognitive functioning did not seem to influence the type of coping. However, subjects with impairment on tasks that assess sustained attention and some aspects of executive function were less prone to adopt positive coping strategies. Cognitive and emotional problems should be carefully monitored, providing prompt diagnosis and treatment as appropriate.
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.
Objective
Recent findings support greater efficacy of early vs. delayed interferon beta (IFNβ) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to ...evaluate the effectiveness of early IFNβ treatment in definite relapsing‐remitting MS (RRMS) and to assess the optimal time to initiate IFNβ treatment with regard to the greatest benefits on disability progression.
Methods
A cohort of 2,570 IFNβ‐treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNβ treatment on risk of reaching a 1‐point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS‐adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings.
Results
The lowest hazard ratios (HRs) for the three PS quintiles–adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1‐point progression in EDSS score (HR = 0.63; 95% CI = 0.48–0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36–0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders.
Interpretation
Greater benefits on disability progression may be obtained by an early IFNβ treatment in RRMS. Ann Neurol 2009;66:513–520
To assess whether neuropsychological tests and MRI measures could be used as predictors of short-term disease evolution in a population of patients with benign multiple sclerosis (B-MS).
The ...definition of B-MS is controversial. Recent data suggest that neuropsychological tests and MRI measures can provide valuable information for a more correct definition and interpretation of B-MS.
Sixty-three patients with B-MS (Expanded Disability Status Scale EDSS < or =3.0 and disease duration > or =15 years) underwent neuropsychological assessment using the Rao's Brief Repeatable Neuropsychological Battery and the Stroop Test. At that time, conventional brain MRI and magnetization transfer (MT) imaging was performed. White matter lesion load, global and regional brain volumes, and MT ratio in lesions and normal-appearing brain were measured. After a mean follow-up of 5 years, patients still having an EDSS score < or =3.5 were classified as still benign, whereas patients who had developed a secondary progressive course or who had an EDSS score > or =4.0 were defined as no longer benign (NLB).
At end of follow-up, 29% of patients were classified as NLB. Male gender (hazard ratio HR = 2.9; 95% confidence interval CI 1.2-7.5; p = 0.02), number of neuropsychological tests failed (HR = 1.4; 95% CI 1.1-1.7; p = 0.003), and T1-weighted lesions (HR = 1.3; 95% CI 1.1-1.5; p = 0.002) were related to NLB status. In a model including these 3 variables, the NLB status was predicted with an accuracy of 82%.
Cognitive assessment and MRI metrics can predict short-term disease evolution in benign multiple sclerosis (B-MS). This information can be useful to correctly identify patients with B-MS.
The definition of benign multiple sclerosis (B-MS) is still controversial. This mainly takes into account the subject's motor ability, with little or no relevance to other important features such as ...cognition. Moreover, no paraclinical markers are currently available to reliably identify patients who will remain benign in the long term.
To assess, by using quantitative magnetic resonance (MR) metrics, differences in tissue damage between B-MS patients after dividing them into two groups on the basis of their cognitive performance.
Forty-seven B-MS patients (Expanded Disability Status Scale score </=3.0 and disease duration >/=15 years) underwent neuropsychological assessment through the Rao Brief Repeatable Battery and the Stroop Test. At that time, B-MS patients underwent conventional brain MR and magnetization transfer (MT) imaging. White matter lesion load, global and regional brain volumes, and MT ratio (MTr) in lesions and normal-appearing brain were measured. Quantitative MR measures were compared in cognitively impaired (CI-MS) and cognitively preserved (CP-MS) patients and in 24 demographically matched healthy controls. Test performance was correlated with MR changes in specific cortical regions.
Eleven patients were classified as CI-MS, and 36 were classified as CP-MS. Both T2-weighted and T1-weighted lesion loads were higher (p = 0.05 and 0.001) in CI-MS than in CP-MS patients. Furthermore, CI-MS patients were characterized by more pronounced decrease in neocortical volume (p = 0.005) and cortical MTr (p = 0.02) values than CP-MS patients. Finally, test performance correlated significantly with MR changes in relevant cortical regions.
Cognitive assessment and quantitative magnetic resonance can help to reliably identify benign multiple sclerosis patients.
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