Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: a 5-year longitudinal study.

BACKGROUND: Cardiovascular diseases (CVDs) are more frequent in multiple sclerosis (MS) patients when compared to controls. In particular, CVDs are linked with higher accumulation of lesions and advanced brain atrophy. OBJECTIVE: To investigate whether CVDs contribute to accelerated lesion accumulation and brain atrophy over 5 years in patients with MS. METHODS: 194 MS patients and 43 controls without neurologic disease were followed for 5 years. Full physical, neurological evaluation, and structured questionnaire investigating CVD and risk factors (hypertension, hyperlipidemia, heart disease, smoking, diabetes, obesity/overweight) were collected using interview-based questionnaire and further cross-reference with electronic medical records. Lesion and brain atrophy outcomes were assessed with 3T MRI. ANCOVA adjusted for age, gender, and disease duration were used accordingly. False discovery rate correction was performed using Benjamini-Hochberg correction. RESULTS: Patients with diagnosis of heart disease showed higher white matter and whole brain volume loss compared to those without (-4.2% vs. -0.7%, P = 0.01 and -3.4% vs. -1.6%, P = 0.01, respectively). The percentage lateral ventricle volume change in MS patients with hypertension was higher compared to non-hypertensive patients (24.5% vs. 14.1%, P = 0.05). Hyperlipidemia, smoking, and obesity/overweight were not associated with progression of MRI-derived outcomes. CVDs did not contribute to larger lesion volume accrual over the 5-year period. The presence of CVDs was not associated with MRI-derived changes in the controls. CONCLUSIONS: Hypertension and heart disease contribute to advanced brain atrophy in MS patients. CVDs did not contribute to additional lesion accrual. CVD comorbidities in MS patients may contribute to neurodegenerative tissue injury that can be detected with brain MRI.

Perceived neuropsychological impairment inversely related to self-reported health and employment in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) patients frequently report cognitive difficulties which impact daily functioning. The objective was to investigate the relationship between patient-reported cognitive impairment and depression, demographic and MS-related variables, and to clarify its impact on self-reported health measures and employment. METHOD: A large two-centre survey included the MS Neuropsychological Screening Questionnaire (MSNQ), the two-question screening tool for depression, vitality, health-related quality of life, the Health-Promoting Lifestyle Profile II and questions assessing social network satisfaction and employment status. RESULTS: Of the 751 respondents (median age 54 years, median Expanded Disability Status Scale 5, 66.2% female), two-thirds reported perceived neuropsychological impairment or depressive symptoms. Whilst depressive symptoms were related to higher MSNQ scores, the MSNQ poorly predicted depression. After correcting for confounders, higher MSNQ scores and depressive symptoms decreased vitality, health-related quality of life and health-promoting behaviours and increased the probability of being socially dissatisfied. In participants below retirement age, higher MSNQ and Expanded Disability Status Scale scores increased the probability of unemployment, whilst depression did not. CONCLUSION: The contribution of the MSNQ to self-reported health measures and its unique explanatory power regarding unemployment suggest that subjective cognitive complaints are connected to subtle, yet meaningful, neuropsychological dysfunction.

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

BACKGROUND AND PURPOSE: While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. METHODS: Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). RESULTS: The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). CONCLUSIONS: The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment.

Multimodal imaging in systemic lupus erythematosus patients with diffuse neuropsychiatric involvement.

OBJECTIVES: The objective of this paper is to investigate conventional and nonconventional brain magnetic resonance imaging (MRI) findings in systemic lupus erythematosus (SLE) patients with diffuse neuropsychiatric involvement (dNPSLE) compared to healthy controls (HCs). METHODS: Twenty-six (26) SLE patients with one or more diffuse NP syndromes related to the central nervous system (CNS) (dNPSLE) and 36 age- and sex-matched HCs were scanned on a 3T MRI using a multimodal imaging approach. Univariate and multivariate analyses were used to determine MRI-specific measure differences between dNPSLE and HCs for lesion burden, tissue-specific atrophy, magnetization transfer ratio (MTR) and diffusion-tensor imaging (DTI) outcomes. RESULTS: In univariate analyses, dNPSLE patients showed significantly increased T1 lesion number (p = .001) and T1-lesion volume (LV, p = .008) compared to HCs. dNPSLE patients showed decreased whole brain volume (p < .0001), gray matter volume (p < .0001), cortical volume (p < .0001) and increased lateral ventricle volume (p = .004) compared to HCs. dNPSLE patients had increased axial diffusivity (AD) of NAWM (p = .008) and NA brain tissue (p = .017) compared to HCs. In the multivariate regression analysis, decreased cortical volume was associated with SLE (R (2) = 0.59, p < .0001). CONCLUSIONS: This study shows that cortical and central atrophy are associated with SLE patients with diffuse CNS syndromes. Microscopic tissue injury in the NAWM on AD DTI measures in SLE patients indicates a predominant reduction of axonal density.

Reports of patients and relatives from the CogniCIS study about cognition in clinically isolated syndrome: what are our patients telling us?

OBJECTIVE: To assess the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) in patients with clinically isolated syndrome (CIS). METHODS: 130 European CIS patients and 60 relatives completed the MSNQ. RESULTS: The mean (SD) MSNQ score for CIS patients was 15.5 (10.8) and for their informants 11.3 (9.6). Neither the CIS patient nor relative MSNQ report scores correlated with any of the cognitive test scores in the Brief Repeatable Battery of Neuropsychological Tests, but they were significantly related to psychosocial scales including depression. CONCLUSIONS: In CIS, patient and relative MSNQ scores are influenced by psychosocial variables rather than actual objective cognitive status. Formal cognitive test assessment is recommended for CIS patients.

Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS).

BACKGROUND: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. OBJECTIVE: To recommend a brief cognitive assessment for multiple sclerosis (MS) that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use. METHODS: An expert committee of twelve members representing the main cultural groups that have so far contributed considerable data about MS cognitive dysfunction was convened. Following exhaustive literature review, peer-reviewed articles were selected to cover a broad spectrum of cultures and scales that targeted cognitive domains vulnerable to MS. Each was rated by two committee members and candidates scales were rated on psychometric qualities (reliability, validity, and sensitivity), international application, ease of administration, feasibility in the specified context, and acceptability to patients. RESULTS: The committee recommended the Symbol Digit Modalities Test, if only 5 minutes was available, with the addition of the California Verbal Learning Test - Second Edition and the Brief Visuospatial Memory Test - Revised learning trials if a further 10 minutes could be allocated for testing. CONCLUSIONS: A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.

Subjective cognitive impairment is related to work status in people with multiple sclerosis.

Background: Unemployment is common among people with multiple sclerosis (pwMS) and has been associated with subjective cognitive difficulties, specifically in memory, attention, and executive functioning. However, longitudinal research on subjective cognitive difficulties and employment is scarce. Objective: We investigated whether subjective cognitive impairment (SCI), based on the clinical cut-off score of the MS Neuropsychological Screening Questionnaire (MSNQ), was associated with work status and negative work events (NWE) at baseline and after 2 years. Moreover, we investigated whether four MSNQ subdomains were related to work status and NWE. Methods: 287 participants (77.4% female, median age = 42 years) completed questionnaires on subjective cognitive functioning, depression, anxiety, and fatigue, and completed the Symbol Digit Modalities Test (SDMT). After baseline comparisons, logistic regression analyses were performed, with work status and NWE at baseline, and employment change and NWE change within 2 years after baseline as dependent variables. Independent variables included SCI and the MSNQ domains. Covariates anxiety, depression, fatigue, and SDMT were added. Results: SCI, depression and anxiety were associated with work status (Nagelkerke R 2 = .286), but only SCI was associated with employment change (Nagelkerke R 2 = .164). No predictors were associated with NWE at baseline or follow-up. In addition, no MSNQ subdomain was related to work status, employment change or NWE. Conclusion: Unemployed pwMS and pwMS with a deteriorated work status reported more cognitive difficulties after 2 years than employed pwMS or pwMS with a stable work status. In addition, depression, and anxiety were associated with work status.

Visual-cognitive processing deficits in pediatric multiple sclerosis.

BACKGROUND: Children with multiple sclerosis (MS) can suffer significant cognitive deficits. This study investigates the sensitivity and validity in pediatric MS of two visual processing tests borrowed from the adult literature, the Brief Visuospatial Memory Test-Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT). OBJECTIVE: To test the hypothesis that visual processing is disproportionately impacted in pediatric MS by comparing performance with that of healthy controls on the BVMTR and SDMT. METHODS: We studied 88 participants (43 MS, 45 controls) using a neuropsychological assessment battery including measures of intelligence, language, visual memory, and processing speed. Patients and demographically matched controls were compared to determine which tests are most sensitive in pediatric MS. RESULTS: Statistically significant differences were found between the MS and control groups on BVMTR Total Learning (t (84) = 4.04, p < 0.001, d = 0.87), BVMTR Delayed Recall (t (84) = 4.45, p < 0.001, d = 0.96), and SDMT (t (38) = 2.19, p = 0.035, d = 0.69). No significant differences were found between groups on confrontation naming or general intellectual ability. Validity coefficients exploring correlation between BVMTR, SDMT, and disease characteristics were consistent with the adult literature. CONCLUSIONS: This study found that BVMTR and SDMT may be useful in assessing children and adolescents with MS.

Employment status monitoring in an Argentinian population of patients with multiple sclerosis: Particularities of a developing country.

BACKGROUND: Multiple sclerosis (MS) is a neurological chronic disease that causes a number of physical, cognitive and emotional symptoms. The identification of these factors will allow mitigating unemployment and improve quality of life of patients. The Buffalo Vocational Monitoring Survey (BVMS) is a tool to characterize Work-Challenged patients. OBJECTIVE: To describe and analyze BVMS data in people with multiple sclerosis (PwMS) from Argentina. To study the association with physical, cognitive and psychiatric morbidity in employed patients, comparing the performance of MS Work-Challenged and MS Work-Stable patients, with and without accommodations. METHODS: 119 MS patients were administered the Argentina adaptation of the BVMS, and completed measures of physical disability, fatigue, depression, cognitive processing speed, memory and verbal fluency. RESULTS: 65.54% of the patients were employed and 19.32% were unemployed, the remaining having roles of housewife, students and disability retirees. Within the employed subgroup, 60.26% were working as employees and 39.74% were self-employed. Cognitive and clinical variables differentiate patients with and without negative events and accommodations (p >  0.05). CONCLUSIONS: This Spanish version BVMS is considered a new tool to monitor employment difficulties in Spanish-speaking MS patients. MS Work-Challenged had a higher depression, fatigue and worse performance in cognitive variables.

Psychometrics and normative data for the Multiple Sclerosis Functional Composite: replacing the PASAT with the Symbol Digit Modalities Test.

The MS Functional Composite (MSFC) is a continuous scale of neurological disability for patients with multiple sclerosis (MS). Cognition is represented by the Paced Auditory Serial Addition Test (PASAT), although the Symbol Digit Modalities Test (SDMT) has been proposed as a promising alternative. MSFC scores were calculated using either the PASAT or the SDMT with the following reference populations: National Multiple Sclerosis Society (NMSS) Task Force, 400 MS patients, and 100 normal controls. A subgroup of 115 patients was followed longitudinally, with a test-retest interval of 2.3 +/- 1.2 years. Pearson correlations were calculated and analyses of variance (ANOVAs) were used to assess relationships among the MSFC components and composite scores, and differences in performance between patients and controls. Longitudinal changes were also assessed. Logistic regression was performed to determine which MSFC scores are most predictive of diagnosis, course, and work disability. All MSFCs had similar test-retest reliability and correlations with other measures including neurological disability, depression, and fatigue. The SDMT showed slightly better validity with respect to predicting diagnosis, course, and work disability, although the amount of variance accounted for was similar for each version of the MSFC. Our data, derived from a large sample of MS patients and normal controls, supports the validity of both PASAT and SDMT versions of the MSFC. Because the SDMT has slightly better predictive validity and has a relatively easier administration procedure, some clinicians and researchers may wish to replace the PASAT with the SDMT in future calculations of the MSFC using the calculation methods provided in this manuscript.

Evaluation of the symbol digit modalities test (SDMT) and MS neuropsychological screening questionnaire (MSNQ) in natalizumab-treated MS patients over 48 weeks.

BACKGROUND AND OBJECTIVES: Brief cognitive tests to monitor cognitive impairment in patients with multiple sclerosis (MS) are needed. METHODS: Performance on monthly administrations of the Symbol Digit Modalities Test (SDMT) and the MS Neuropsychological Questionnaire (MSNQ) was assessed in 660 patients with MS in 21 countries (109 sites) for 48 weeks in an open-label, safety-extension study of natalizumab. RESULTS: At baseline, the cohort's mean age was 40.1 years, 67.6% were female and the median Expanded Disability Status Scale score was 2.5. Test-retest correlations were high for both SDMT (range 0.89 for weeks 0-4 to 0.96 for weeks 44-48) and MSNQ (0.82 for weeks 0-4 to 0.93 for weeks 44-48). There were no statistically significant effects of geographic region. While SDMT scores improved by 15 points over 48 weeks (p < 0.0001), incremental monthly changes were small (effect size d < 0.3). Similar results were obtained on the MSNQ except that scores moved downward, suggesting fewer cognitive complaints over 48 weeks (p < 0.0001), but again the incremental monthly changes were small (d <-0.2). CONCLUSIONS: These results replicate earlier work in a smaller cohort treated with conventional disease-modifying therapy, and support the reliability of the SDMT and MSNQ as potential screening for monitoring tools for cognition over time.

Memory impairment in multiple sclerosis: correlation with deep grey matter and mesial temporal atrophy.

BACKGROUND: MRI research in multiple sclerosis (MS) samples reveals pathology in both the cerebral cortex and deep grey matter (DGM). The classical subcortical dementia hypothesis has been ascribed to MS and is supported by studies highlighting the role of thalamic atrophy in neuropsychological outcomes. However, the importance of mesial temporal lobe (MTL) atrophy in MS is largely untested and poorly understood. New structural imaging techniques permit volumetric measures of multiple regions within the MTL lobe and DGM. OBJECTIVE: To determine the relative importance of MTL and DGM structures in predicting MS performance on memory tests presented in the auditory/verbal and visual/spatial spheres. METHODS: Cross sectional analysis of 50 patients with MS undergoing structural brain MRI and neuropsychological testing. Using Freesurfer software, the volumes of the MTL (hippocampus, amygdala) and DGM (thalamus, caudate) structures were calculated and compared with control values. Neuropsychological testing contributed measures of new learning, delayed recall and recognition memory, in the auditory/verbal and visual/spatial memory modalities. RESULTS: Significant correlations between lower regional volume and poorer test performance were observed across all memory tests. For measures of free recall or new learning, DGM volumes were most strongly predictive of outcomes. In contrast, measures of recognition memory were predicted only by MTL volumetric measures. CONCLUSION: For the first time, the predictive validity of MTL and DGM atrophy were simultaneously compared with MS using reliable and validated neuropsychological measures. This study found that both compartments play significant but different roles in the amnesia of MS.

Effects of l-amphetamine sulfate on cognitive function in multiple sclerosis patients.

We evaluated the effects of the levo (l) enantiomer of amphetamine sulfate on cognitive function in multiple sclerosis (MS) patients. Using a counterbalanced within-subjects design, 19 MS patients received four single-dose administrations of placebo, 15 mg, 30 mg, or 45 mg of l-amphetamine. Neuropsychological tests measuring processing speed and memory served as the primary outcomes. Performance on tests of processing speed were improved following the 45 mg condition and the largest effects were observed on the Symbol Digit Modalities Test, which measures visual processing speed and working memory. While episodic memory test effects were in the expected direction, the findings were not statistically significant. These preliminary findings show promise for the use of l-amphetamine for the symptomatic treatment of slowed mental processing in MS. Further placebo-controlled trials are needed to confirm these findings.

Impact of Focal White Matter Damage on Localized Subcortical Gray Matter Atrophy in Multiple Sclerosis: A 5-Year Study.

BACKGROUND AND PURPOSE: It is unclear to what extent subcortical gray matter atrophy is a primary process as opposed to a result of focal white matter damage. Correlations between WM damage and atrophy of subcortical gray matter have been observed but may be partly attributable to indirect relationships between co-occurring processes arising from a common cause. Our aim was to cross-sectionally and longitudinally characterize the unique impact of focal WM damage on the atrophy of connected subcortical gray matter regions, beyond what is explainable by global disease progression. MATERIALS AND METHODS: One hundred seventy-six individuals with MS and 47 healthy controls underwent MR imaging at baseline and 5 years later. Atrophy and lesion-based disruption of connected WM tracts were evaluated for 14 subcortical gray matter regions. Hierarchic regressions were applied, predicting regional atrophy from focal WM disruption, controlling for age, sex, disease duration, whole-brain volume, and T2-lesion volume. RESULTS: When we controlled for whole-brain volume and T2-lesion volume, WM tract disruption explained little additional variance of subcortical gray matter atrophy and was a significant predictor for only 3 of 14 regions cross-sectionally (ΔR2 = 0.004) and 5 regions longitudinally (ΔR2 = 0.016). WM tract disruption was a significant predictor for even fewer regions when correcting for multiple comparisons. CONCLUSIONS: WM tract disruption accounts for a small percentage of atrophy in connected subcortical gray matter when controlling for overall disease burden and is not the primary driver in most cases.

MRI T2 hypointensity of the dentate nucleus is related to ambulatory impairment in multiple sclerosis.

OBJECTIVES: MRI T2 hypointensity in multiple sclerosis (MS) gray matter, suggesting iron deposition, is associated with physical disability, disease course, lesion load, and brain atrophy. Ambulatory dysfunction limits quality of life; however correlation with conventional MRI remains poor. METHODS: Normalized intensity on T2-weighted images was obtained in the basal ganglia, thalamus, red nucleus, and dentate nucleus in 47 MS patients and 15 healthy controls. Brain T1-hypointense and FLAIR-hyperintense lesion volume, third ventricle width, brain parenchymal fraction and timed 25 foot walk (T25FW) were measured in the MS group. RESULTS: T2 hypointensity was present throughout gray matter in MS vs. controls (all p<0.01). Dentate T2 hypointensity was the only MRI variable significantly correlated with T25FW (Pearson r=-0.355, p=0.007) and was also the best MRI correlate of physical disability (EDSS) score in regression modeling (r=-0.463, R(2)=0.223, p=0.004). CONCLUSIONS: T2 hypointensity is present in subcortical gray matter nuclei in patients with MS vs. normal controls. Dentate nucleus T2 hypointensity is independently related to ambulatory impairment and disability, accounting for more variance than conventional lesion and atrophy measures. This study adds more weight to the notion that T2 hypointensity is a clinically relevant marker of tissue damage in MS.

Iron and volume in the deep gray matter: association with cognitive impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: There is a well-established correlation between deep gray matter atrophy and cognitive dysfunction in MS. However, the cause of these signs of neurodegeneration is poorly understood. Iron accumulation in the deep gray matter is higher in patients with MS compared with age- and sex-matched healthy controls, and could contribute to disease progression. Our objective was to evaluate the relationship between iron and cognition in several deep gray matter structures while accounting for the influence of volume loss. MATERIALS AND METHODS: Eighty-five patients with MS and 27 healthy volunteers underwent 3T MR imaging and neuropsychological examination. We used SWI filtered phase to analyze the mean phase of low-phase voxels, indicative of abnormal iron accumulation. RESULTS: Correlations between mean phase of low-phase voxels and cognitive tests were found in the caudate nucleus (r = 0.240 and 0.232), putamen (r = 0.368, 0.252, and 0.238), globus pallidus (r = 0.235), and pulvinar nucleus of thalamus (r = 0.244, 0.255, and 0.251) (P < .05). However, correlations between structure volume and cognition were more robust. Furthermore, the introduction of structure volume into hierarchical regression analyses after iron metrics significantly improved most models, and mean phase of low-phase voxels did not account for significant variance after volume. CONCLUSIONS: These findings suggest that iron accumulation plays a significant, if minor, role in MS cognitive decline.

Cognitive and White Matter Tract Differences in MS and Diffuse Neuropsychiatric Systemic Lupus Erythematosus.

BACKGROUND AND PURPOSE: Multiple sclerosis and neuropsychiatric systemic lupus erythematosus are autoimmune diseases with similar CNS inflammatory and neurodegenerative characteristics. Our aim was to investigate white matter tract changes and their association with cognitive function in patients with MS and those with neuropsychiatric systemic lupus erythematosus compared with healthy controls by using diffusion tensor imaging. MATERIALS AND METHODS: Thirty patients with relapsing-remitting MS and 23 patients with neuropsychiatric systemic lupus erythematosus matched for disease severity and duration and 43 healthy controls were scanned with 3T MR imaging. The DTI was postprocessed, corrected for lesions, and analyzed with tract-based spatial statistics. Cognitive assessment included examination of processing speed; visual, auditory/verbal, and visual-spatial memory; and sustained attention and executive function. Differences were considered significant at P < .05. RESULTS: Tract-based spatial statistics analysis revealed significantly decreased fractional anisotropy and increased mean diffusivity in patients with MS compared with healthy controls, decreased fractional anisotropy in patients with MS compared with those with neuropsychiatric systemic lupus erythematosus, and an increased mean diffusivity in patients with neuropsychiatric systemic lupus erythematosus compared with healthy controls. Patients with MS showed decreased fractional anisotropy throughout central WM pathways, including the corpus callosum and the inferior longitudinal and fronto-occipital fasciculi compared with those with neuropsychiatric systemic lupus erythematosus. Altered cognitive scores in patients with MS were significantly associated with decreased fractional anisotropy and increased mean diffusivity in all examined domains, while in patients with diffuse neuropsychiatric systemic lupus erythematosus, only decreased fractional anisotropy in the superior WM pathways showed significant association with executive function. CONCLUSIONS: Patients with MS and neuropsychiatric systemic lupus erythematosus showed widespread WM tract alterations outside overt lesions, though more severe changes were identified in patients with MS. The WM tract changes were associated with cognitive dysfunction in all explored domains only in patients with MS.

Whole-brain atrophy in multiple sclerosis measured by two segmentation processes from various MRI sequences.

Recent MRI and pathologic studies have drawn attention to the destructive nature of the multiple sclerosis (MS) disease process, including the early occurrence of axonal and neuronal loss, leading to macroscopic brain and spinal cord atrophy. Measurement of brain atrophy from MRI has emerged as a potential outcome measure and marker of disease severity in MS and neurodegenerative diseases such as Alzheimer's. However, the optimal method for quantifying atrophy has not been established, including the choice of pulse sequence and segmentation algorithm employed. Using two different MRI scanners to ensure generalizability of results, we compared the reproducibility of four pulse sequences and two analysis methods (fully automated [FA] and semi-automated [SA]) when obtaining brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, in patients with MS (n=13) and normal controls (n=2). In order to ensure the validity of our fully automated analysis technique, we also used it to evaluate the atrophy rate over nine months in 57 MS patients from the placebo arm of a clinical trial. All pulse sequences were capable of yielding reproducibility of around 1% coefficient of variation (CoV) or better. The best reproducibility was obtained using 2D multi-slice sequences (conventional spin echo [SE] and fluid-attenuated inversion recovery [FLAIR]), with fully automated analysis. Fully automated analysis of the longitudinal data (conventional spin echo) showed an atrophy rate of -0.5% change in BPF per year, in line with previous findings from a similar cohort of patients. In conclusion, BPF measurement is affected by both pulse sequence and segmentation method. Automated measurement has high reproducibility especially when 2D sequences are used. Semi-automated measurement may have increased accuracy, but with a decreased efficiency and reliability.

Cognitive and neuropsychiatric disorders among multiple sclerosis patients from Latin America: Results of the RELACCEM study.

BACKGROUND: Cognitive impairment and psychiatric symptoms impact many aspects of the lives of people with multiple sclerosis [MS]. This literature is based largely on North American and Western European samples, and little is known about these aspects of MS disability in Latin America. OBJECTIVE: RELACCEM is a longitudinal, multicenter study including MS centers in Argentina, Chile, Columbia, Venezuela, Uruguay and Mexico. The goal is to determine the prevalence of cognitive impairment (two or more cognitive domains under the 5th percentile of healthy controls performance) and the full range of neuropsychiatric symptoms in these regions, and how these symptoms relate to caregiver burden and employment. METHODS: Participants were 110 patients with relapsing-remitting [RR] course and less than five years of disease duration. Thirty-four healthy controls were also recruited. All participants were evaluated in one of 14 specialized centers. RESULTS: In additional to overall neurological disability, both cognition and neuropsychiatric symptoms distinguished patients and controls. The prevalence of cognitive impairment was 34.5% and 20.9% presented with clinically significant neuropsychiatric symptomatology. Cognitive impairment was a significant predictor of employment status. CONCLUSIONS: This is the first multicenter epidemiological study of MS-associated cognitive and neuropsychiatric symptoms in Latin America. Results indicate that cognitive dysfunction and psychiatric decline symptoms, fatigue, depression and caregiver burden are already apparent at an early stage of the disease. The presence of neuropsychiatric abnormalities indicates the need for appropriate interventions as early as possible to mitigate psychosocial consequences of caregiver burden.

Regression-based norms improve the sensitivity of the National MS Society Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS).

The National Multiple Sclerosis Society Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS) was designed to detect cognitive impairment in children and adolescents with multiple sclerosis. One weakness of the battery is the reliance on published manual-based normative samples varying in size and quality. These primary sources base interpretation on discrete age bands, a practice which may be particularly problematic during periods of rapid development in childhood and adolescence. A further impediment to valid NBPMS interpretation is the lack of control for demographic factors other than age. We endeavored to develop regression-based norms for the NBPMS by gathering a demographically balanced sample of 102 healthy control children and using their performance to derive normalization, controlling for multiple demographic variables (i.e., age, age(2), gender, parent education). The regression-based normative equations were applied to the performance of 51 children with MS. For many of the major test scores, the regression-based norms more readily detected impairment. As in the case of adult MS, these results indicate that regression-based norms offer interpretive benefits over their manual-based counterparts.