A new assessment tool for patients with multiple sclerosis from Spanish-speaking countries: validation of the Brief International Cognitive Assessment for MS (BICAMS) in Argentina.

BACKGROUND: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is an international assessment tool for monitoring cognitive function in multiple sclerosis (MS) patients. BICAMS comprises the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test - Second Edition (CVLT II) and the Brief Visuospatial Memory Test - Revised (BVMT-R). Our objective was to validate and assess the reliability of BICAMS as applied in Argentina and to obtain normative data in Spanish for this population. METHOD: The sample composed of 50 MS patients and 100 healthy controls (HC). In order to test its reliability, BICAMS was re-administered in a subset of 25 patients. RESULTS: The sample's average age was 43.42 ± 10.17 years old, and average years of schooling were 14.86 ± 2.78. About 74% of the participants were women. The groups did not differ in age, years of schooling, or gender. The MS group performed significantly worse than the HC group across the three neuropsychological tests, yielding the following Cohen's d values: SDMT: .85; CVLT I: .87; and BVMT-R: .40. The mean raw scores for Argentina normative data were as follows: SDMT: 56.71 ± 10.85; CVLT I: 60.88 ± 10.46; and BVMT-R: 23.44 ± 5.84. Finally, test-retest reliability coefficients for each test were as follows: SDMT: r = .95; CVLT I: r = .87; and BVMT-R: r = .82. CONCLUSION: This BICAMS version is reliable and useful as a monitoring tool for identifying MS patients with cognitive impairment.

Latent profile analysis of regression-based norms demonstrates relationship of compounding MS symptom burden and negative work events.

OBJECTIVE: We endeavored to clarify how distinct co-occurring symptoms relate to the presence of negative work events in employed multiple sclerosis (MS) patients. Latent profile analysis (LPA) was utilized to elucidate common disability patterns by isolating patient subpopulations. METHOD: Samples of 272 employed MS patients and 209 healthy controls (HC) were administered neuroperformance tests of ambulation, hand dexterity, processing speed, and memory. Regression-based norms were created from the HC sample. LPA identified latent profiles using the regression-based z-scores. Finally, multinomial logistic regression tested for negative work event differences among the latent profiles. RESULTS: Four profiles were identified via LPA: a common profile (55%) characterized by slightly below average performance in all domains, a broadly low-performing profile (18%), a poor motor abilities profile with average cognition (17%), and a generally high-functioning profile (9%). Multinomial regression analysis revealed that the uniformly low-performing profile demonstrated a higher likelihood of reported negative work events. CONCLUSIONS: Employed MS patients with co-occurring motor, memory and processing speed impairments were most likely to report a negative work event, classifying them as uniquely at risk for job loss.

Regression-Based Norms for the Brief Visuospatial Memory Test-Revised in Italian population and application in MS patients.

OBJECTIVE: The Brief Visuospatial Memory Test-Revised (BVMT-R) is one of the most widely used tests for the assessment of learning and memory in the visual/spatial domain. The aim of this study was to use multiple regression to derive normative data for the use of BVMT-R in an Italian population. METHOD: We employed a regression-based norms procedure to maximally utilize a relatively small sample while controlling for a variety of demographic factors in addition to age. Additionally, we used these norms to compare the performance of Italian healthy controls with patients diagnosed with multiple sclerosis (MS), thereby providing evidence of the method's validity. RESULTS: A total of 200 healthy volunteers and 70 MS patients participated in this study and completed the BVMT-R according to the published procedures. Regression-based norms were generated for the Italian sample and are presented herein. CONCLUSIONS: Using these norms, the performance of the MS patients was found to be significantly worse than that of the controls.

Factor Structure, Internal Consistency, and Screening Sensitivity of the GARS-2 in a Developmental Disabilities Sample.

The Gilliam Autism Rating Scale-Second Edition (GARS-2) is a widely used screening instrument that assists in the identification and diagnosis of autism. The purpose of this study was to examine the factor structure, internal consistency, and screening sensitivity of the GARS-2 using ratings from special education teaching staff for a sample of 240 individuals with autism or other significant developmental disabilities. Exploratory factor analysis yielded a correlated three-factor solution similar to that found in 2005 by Lecavalier for the original GARS. Though the three factors appeared to be reasonably consistent with the intended constructs of the three GARS-2 subscales, the analysis indicated that more than a third of the GARS-2 items were assigned to the wrong subscale. Internal consistency estimates met or exceeded standards for screening and were generally higher than those in previous studies. Screening sensitivity was .65 and specificity was .81 for the Autism Index using a cut score of 85. Based on these findings, recommendations are made for instrument revision.

Fatigue and depression in children with demyelinating disorders.

Fatigue and depression have been shown to be significant problems in children with multiple sclerosis. The rate at which these conditions occur in children with other acquired demyelinating syndromes is unknown. In this cross-sectional study, the authors evaluated 49 children with demyelinating disorders (multiple sclerosis and acute disseminated encephalomyelitis) and 92 healthy controls for depression and/or fatigue using the Behavior Assessment System for Children, Second Edition behavior and mood rating scale and Varni PedsQL Multidimensional Fatigue Scale. The parents of acquired demyelinating syndrome patients were more likely to report elevated depressive symptoms (30.8% vs 10.8%, P = .008). Elevated parent and self-reported total fatigue (25% vs 0%, P < .001, 26.7% vs 8.6%, P = .024) was seen in the patient cohort. The authors conclude that fatigue and depression are far more common in children with acquired demyelinating syndromes than in controls. Clinical attention to and implementation of effective therapies oriented toward these conditions in children with acquired demyelinating syndromes is needed.

Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study.

Multiple sclerosis (MS) causes cognitive impairment including slowed processing speed and problems with learning and memory. Stimulants are attractive candidates for improving mental speed but carry risk of addiction and other adverse behavioral effects. Lisdexamfetamine dimesylate (LDX) is a D-amphetamine prodrug currently approved for attention deficit (hyperactivity) disorder with the potential to be better tolerated due to its prolonged clinical effect. This phase II placebo-controlled, double-blind study aimed to assess the safety and efficacy of LDX in cognitively impaired MS patients. Subjects were patients with clinically definite MS, aged 18-56 years, and impaired on either of two primary outcomes: the Symbol Digit Modalities Test (SDMT) or the Paced Auditory Serial Addition Test (PASAT). Both SDMT and PASAT are measures of cognitive processing speed. Of 174 MS patients screened, 63 were randomized to 30 mg of LDX or placebo in a 2:1 fashion; the dose was increased as tolerated to 70 mg over 4 weeks and then maintained for another 4 weeks. Secondary outcomes were the Brief Visuospatial Memory Test Revised (BVMTR), the California Verbal Learning Test 2nd edition (CVLT2), both measures of episodic memory, and the Behavioral Rating Inventory of Executive Function for adults (BRIEF-A), a self-report measure of executive function. Fatigue and depression were also evaluated. There was significant improvement in the SDMT score (+4.6 vs. +1.3) and CVLT2 score (+4.7 vs. -0.9) in the LDX group compared with the placebo group among the 49 completers. There was no change on the other outcomes. A high proportion of both LDX-treated and placebo-treated subjects reported adverse events (73.5 % vs. 68.4 %). However, there were no serious adverse events noted in the study. These preliminary data indicate that LDX has the potential to be an efficacious treatment for MS patients with cognitive impairment.

Reliability and equivalence of alternate forms for the Symbol Digit Modalities Test: implications for multiple sclerosis clinical trials.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), but is seldom assessed in clinical trials investigating the effects of disease-modifying therapies. The Symbol Digit Modalities Test (SDMT) is a particularly promising tool due to its sensitivity and robust correlation with brain magnetic resonance imaging (MRI) and vocational disability. Unfortunately, there are no validated alternate SDMT forms, which are needed to mitigate practice effects. OBJECTIVE: The aim of the study was to assess the reliability and equivalence of SDMT alternate forms. METHODS: Twenty-five healthy participants completed each of five alternate versions of the SDMT - the standard form, two versions from the Rao Brief Repeatable Battery, and two forms specifically designed for this study. Order effects were controlled using a Latin-square research design. RESULTS: All five versions of the SDMT produced mean values within 3 raw score points of one another. Three forms were very consistent, and not different by conservative statistical tests. The SDMT test-retest reliability using these forms was good to excellent, with all r values exceeding 0.80. CONCLUSIONS: For the first time, we find good evidence that at least three alternate versions of the SDMT are of equivalent difficulty in healthy adults. The forms are reliable, and can be implemented in clinical trials emphasizing cognitive outcomes.

Cognition and physical disability in predicting health-related quality of life in multiple sclerosis.

Many studies have shown that multiple sclerosis (MS) has a significant impact on patient health-related quality of life (HRQOL), but the relative contributions of physical versus cognitive disability are not well established. Most studies have relied on HRQOL outcomes that depend largely on patient mood, life satisfaction, and personal happiness. The Sickness Impact Profile (SIP) is a measure of HRQOL known for its relatively strong emphasis on task completion and activities of daily living. As such, the SIP may be less influenced by depression. We sought to determine the relative influence of physical disability and cognition, above and beyond demographic and disease variables, in predicting HRQOL. Patients (n = 132) and healthy controls (n = 26) underwent complete neuropsychological evaluation using the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery and a series of self-report measures assessing depression, fatigue, and HRQOL. The SIP was also administered. Correlation analysis and group comparisons revealed significant associations between cognition and HRQOL outcomes. Logistic regression models comparing the Expanded Disability Status Scale (EDSS) and cognitive tests in predicting poor physical HRQOL retained both EDSS and Symbol Digit Modalities Test (SDMT) performance, while models predicting poor psychosocial and poor overall HRQOL retained only the SDMT. These findings support cognition as a significant predictor of overall HRQOL, psychosocial HRQOL, and, interestingly, physical HRQOL.

Anxiety and depression in children with HFASDs: symptom levels and source differences.

The purpose of this study was to: (1) examine symptom levels of anxiety and depression in children with high-functioning autism spectrum disorders (HFASDs) compared with matched control children using child self-reports and parent ratings; and (2) examine source differences within the two condition groups. An overall multivariate effect indicated significantly elevated depression and anxiety symptoms for children with HFASDs based on parent reports; however no significant between-group differences based on child self-reports. Within-condition source comparisons (parent vs. child) revealed a significant multivariate effect indicating a significant difference in symptoms of depression and anxiety for the HFASD group but none for the control. Correlations between parent and child reports for the HFASD group suggested some positive association between child-reports and parent-reports for depressive symptoms only; however, the difference in average scores reflected a substantial discrepancy in the magnitude of symptoms by rater. Implications for clinical assessment and future research are provided.

RCT of a manualized social treatment for high-functioning autism spectrum disorders.

This RCT examined the efficacy of a manualized social intervention for children with HFASDs. Participants were randomly assigned to treatment or wait-list conditions. Treatment included instruction and therapeutic activities targeting social skills, face-emotion recognition, interest expansion, and interpretation of non-literal language. A response-cost program was applied to reduce problem behaviors and foster skills acquisition. Significant treatment effects were found for five of seven primary outcome measures (parent ratings and direct child measures). Secondary measures based on staff ratings (treatment group only) corroborated gains reported by parents. High levels of parent, child and staff satisfaction were reported, along with high levels of treatment fidelity. Standardized effect size estimates were primarily in the medium and large ranges and favored the treatment group.

BASC-2 PRS profiles for students with high-functioning autism spectrum disorders.

BASC-2 PRS profiles of 62 children with high-functioning autism spectrum disorders (HFASDs) were compared with those of 62 typically-developing children matched by age, gender, and ethnicity. Results indicated that, except for the Somatization, Conduct Problems, and Aggression scales, significant differences were found between the HFASD and typically-developing groups on all PRS scores. Mean HFASD scores were in the clinically significant range on the Behavioral Symptoms Index, Atypicality, Withdrawal, and Developmental Social Disorders scales. At-risk range HFASD means were obtained on the Adaptive Skills composite, all adaptive scales, remaining content scales (except Bullying), and Hyperactivity, Attention Problems, and Depression clinical scales. Screening indices suggested that the Developmental Social Disorders scale was highly effective in differentiating between the two groups.