Non-pharmacological randomized intervention trial for the management of neuropsychological symptoms in outpatients with progressive multiple sclerosis.

PURPOSE: Despite typically more pronounced cognitive and mental health issues in progressive disease courses of multiple sclerosis (PMS), rehabilitation research in this subgroup is rare. The efficacy of two non-pharmacological interventions with positive results from prior investigations was therefore examined in PMS specifically. METHODS: Persons with PMS (pwPMS) received either computerized cognitive training (BrainStim), standardized cognitive-behavioral group sessions (Metacognitive Training [MaTiMS]), or a combination of both in an ambulatory setting. Neuropsychological assessment was conducted before and after the four-week intervention. RESULTS: 37 participants (13 with primary/24 with secondary PMS, meanage = 52.87, SDage = 7.11, meanEDSS = 4.02, SDEDSS = 1.35) entered analyses. The BrainStim group improved in immediate and delayed verbal memory, recognition, verbal working memory, and perceived cognitive deficits while experiencing increased anxiety post-intervention. MaTiMS participants reported high program satisfaction and less cognitive difficulties at retest. The Combination group performed better in immediate and delayed verbal memory, and in information processing speed after training. Descriptive data further indicated positive effects on anxiety and depression in the MaTiMS and Combination group. CONCLUSIONS: While objective cognitive performance improved when explicitly trained, psychoeducative sessions contributed to subjective mental health. The combination of both approaches is thus suggested, considering the specific needs of pwPMS treated in an ambulatory setting.

Supporting brain health in multiple sclerosis: exploring the potential of neuroeducation combined with practical mindfulness exercises in the management of neuropsychological symptoms.

OBJECTIVE: We aimed at examining the effects of a known metacognitive training in MS (MaTiMS) and its modification with an additional neuroeducational module and mindfulness-based exercises (MaTiMS-modified) on neuropsychiatric and cognitive outcomes in people with progressive multiple sclerosis (pwpMS). Exploratively, we investigated whether the modification may show an additional benefit. METHODS: Both interventions were administered in small groups of ambulatory patients. Neuropsychological testing before and after the 3- to 4-week intervention phase comprised patient reported outcomes and cognitive tests. After 3, 6 and 12 months, participants completed online surveys. Analysis of change scores (between baseline and retest) with t-tests (Mann-Whitney U and Wilcoxon tests, respectively) and mixed ANCOVAs with repeated measures for comparison of both interventions were conducted. RESULTS: A total of 65 pwpMS turned to a final sample of 50 (n = 15 excluded due to drop-outs, occurrence of relapse or steroid treatment). Change scores within MaTiMS revealed no significant effect on the PDQ-20 total score and only a significant effect on the subscale retrospective memory lasting 3 months with a moderate effect size. In contrast, MaTiMS-modified revealed a highly significant change in PDQ-20 total compared to baseline and significant improvements with small to moderate effect sizes on all PDQ-20 subscales (lasting until 3 months), in self-efficacy, stress, visuo-spatial working memory (moderate effect sizes), and fatigue (small effect size). While no interaction effect between time and group could be revealed, a significant main effect for time was found in PDQ-20 total. CONCLUSION: Both MaTiMS and MaTiMS-modified positively affected perceived cognitive deficits. However, our data speak in favor of additional benefits by adding neuroeducational and mindfulness-based exercises thus being valuable methods to support brain health including self-efficacy, perceived stress, and fatigue, even in patients with a chronic and progressive brain disease.

Association of Retinal Layer Thickness With Cognition in Patients With Multiple Sclerosis.

OBJECTIVE: Retinal layer thickness (RLT) measured by optical coherence tomography (OCT) is considered a noninvasive, cost-efficient marker of neurodegeneration in multiple sclerosis (MS). We aimed to investigate associations of RLT with cognitive performance and its potential as indicator of cognitive status in patients with MS by performing generalized estimating equation (GEE) analyses. METHODS: In this cross-sectional study, patients with at least mild signs of cognitive impairment were examined by OCT as well as by the Brief International Cognitive Assessment for MS and tests assessing attention and executive functions (Trail Making Test [TMT] A and B). Associations of these factors were investigated using GEE models controlling for demographic and disease-related factors and correcting for multiple testing. RESULTS: A total of 64 patients entered the study. In the final sample (n = 50 [n = 14 excluded due to missing data or drop-outs]; n = 44 relapsing-remitting MS and n = 6 secondary progressive MS, mean Expanded Disability Status Scale score = 2.59 [SD = 1.17], disease duration [median] = 7.34 [interquartile range = 12.1]), 36.0% were cognitively impaired. RLT of the macular retinal nerve fiber layer was associated with performance in TMT-B (ß = -0.259). Analyses focusing on the upper and lower tertile of RLT additionally revealed associations between macular ganglion cell-inner plexiform layer and TMT-B and verbal short-term memory and learning, respectively. CONCLUSION: In patients with MS, at less advanced disease stages, RLT was especially associated with cognitive flexibility promoting OCT as a potential marker advocating further extensive neuropsychological examination.

[Clinical practicability of the cognitive screening battery BICAMS in patients with multiple sclerosis: results of the feasibility study in Germany]. / Klinische Umsetzbarkeit der kognitiven Screeningbatterie BICAMS bei Patienten mit Multipler Sklerose: Ergebnisse der Machbarkeitsstudie in Deutschland.

BACKGROUND: Patients with multiple sclerosis (MS) suffer from cognitive impairment in 40-70% of the cases. There is evidence that the cognitive status is predictive for working ability and early retirement. Regular assessment of cognitive functionality is therefore urgently needed. PURPOSE: The German validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was evaluated in a multicentric way with respect to its feasibility in private neurological centers across Germany. METHODS: Physician assistants were trained with respect to application and scoring of BICAMS. All scored test materials were evaluated by independent neuropsychological experts. RESULTS: A total of 1606 BICAMS datasets were collected from 65 neurological centers. Of these 1573 datasets were analyzed of which 49.7% were correctly applied and scored while mistakes in application, scoring and transformation were found in 50.3%. Interrater reliability for each subtest was found to be ICC [Formula: see text] 0.953 when datasets containing mistakes were excluded. DISCUSSION: In general, BICAMS is highly recommended to be applied in standard clinical care; however, it should be emphasized that although the interrater reliability in the final sample was high, serious mistakes were found in 50.3% of cases. From these findings we conclude that nonpsychological staff have to be even more intensively trained and supervised by experts in the application and scoring of BICAMS.

Mental symptoms in MS (MeSyMS): Development and validation of a new assessment.

BACKGROUND: Patients with Multiple Sclerosis (MS) have an increased risk of suffering from mental and neuropsychiatric symptoms. So far, a fundamental problem in the clinical care of MS patients is that these symptoms are underdiagnosed and, as a consequence, often remain untreated. Present assessment tools have not been developed to be applied in patients with MS. This study aims to develop and validate a new questionnaire to identify disease-related mental symptoms in MS patients. METHODS: A questionnaire has been developed by including the following subscales: social and emotional health problems, anxiety, and depression. To evaluate test quality and internal consistency, an item analysis has been conducted. After matching MS patients and control subjects on age and gender, we conducted group comparisons, a Receiver Operating Characteristic (ROC) Curve analysis and a binary logistic regression model. RESULTS: In total, 314 MS patients and 100 matched control subjects were analysed. After performed item analysis, the questionnaire revealed an excellent internal consistency (α=0.94). Compared to control subjects, MS patients showed significant mental health problems in all three dimensions. In comparison to the subscales, the dimension of social and emotional health problems revealed the highest accuracy (AUC = 0.75; d = 0.948) and turned out to be the only scale that reliably differentiated between the groups. CONCLUSIONS: MeSyMS constitutes a valid screening instrument to detect mental symptoms in MS. Social and emotional health problems turned out to be the most important aspect when identifying disease-related mental health symptoms in MS.

Working ability in individuals with different disease courses of multiple sclerosis: Factors beyond physical impairment.

BACKGROUND: Experiencing a decrease in working ability or even becoming unemployed is common in patients with multiple sclerosis (MS) and has a detrimental impact on the individual's quality of life, self-esteem, and on society's economic burden. Physical disability is still considered the most important predictor for patients' inability to work. This study aims to confirm and extend findings from prior studies indicating the additional importance of other demographical and clinical information accessible within a routine patient evaluation, placing particular emphasis on the inclusion of cognitive and neuropsychiatric measures, as well as on potential disease course differences. METHODS: 159 MS patients (84 with a relapsing disease course (RMS); 75 with a progressive disease course (PMS)) were examined with the Brief International Cognitive Assessment for MS (BICAMS) battery, mood and fatigue questionnaires, and screened for subjectively experienced cognitive problems as well as for various person- and disease-related information (age, sex, education, age at diagnosis, disease duration, immunotherapy, number and nature of comorbidities, smoking and alcohol intake, sleep disturbances). These measures, along with Expanded Disability Status Scale (EDSS) scores were compared between unemployed, part- and full-time working patients. Significant variables were further entered into hierarchical regression models predicting employment status (employed vs. unemployed) as well as weekly hours at work in each disease subtype, respectively. RESULTS: In patients with RMS, unemployed patients had higher EDSS scores, reported a higher number of comorbidities, more frequent past depressive episodes, a higher level of fatigue, and performed worse on the Symbol-Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test revised (BVMT-R). Besides EDSS, unemployment was predicted by SDMT, while weekly hours at work were further determined by the number of comorbidities, BVMT-R, and disease duration. In patients with PMS, unemployed patients also had higher EDSS scores, were younger at diagnosis, and showed a decreased performance in SDMT and the Rey Verbal Learning and Memory Test German version (Verbaler Lern- und Merkfaehigkeitstest; VLMT). Employment status as well as weekly working hours were both predicted by VLMT, educational level, and disease duration beyond EDSS in patients with PMS, while depressive episodes additionally impacted on employment status. CONCLUSIONS: Objectively assessed cognitive functions, neuropsychiatric symptoms (i.e. a history of depressive episodes, fatigue) as well as some specific clinical data (disease duration, comorbidities) add substantial value in the evaluation of working ability beyond physical disability. Since unemployment is associated with different major factors among disease courses, more comprehensive and customized assessments are needed to refine characterization of individual work ability and to adjust interventional strategies targeting employment maintenance.

Serum neurofilament light chain: No clear relation to cognition and neuropsychiatric symptoms in stable MS.

OBJECTIVE: To explore the hypothesis that serum neurofilament light chain (sNfL) indicative of neuroaxonal damage may improve precise disease profiling with regard to cognition and neuropsychiatric symptoms, we analyzed potential associations of sNfL levels with cognitive test scores, fatigue, depression, and anxiety. METHODS: Patients with relapsing-remitting and secondary progressive MS (SPMS) underwent an elaborated assessment including MRI, various cognitive tests, and patient-reported outcomes. We determined sNfL levels by single molecule array (Simoa) assay. Relationships between sNfL, cognition, neuropsychiatric symptoms, and demographical data were analyzed using correlations, group comparisons, and regressions. RESULTS: In 45 clinically stable patients with MS (Expanded Disability Status Scale = 2.73 ± 1.12, disease duration = 10.03 ± 7.49 years), 40.0% were cognitively impaired. Mean sNfL levels were 16.02 ± 10.39 pg/mL, with higher levels in the SPMS subgroup (p = 0.038). sNfL levels did reliably link neither with the investigated cognitive and affective parameters nor with fatigue levels. The only relationship found in a small subgroup of patients with SPMS (n = 7) with visuospatial learning (r = -0.950, p = 0.001) and memory (r = -0.813; p = 0.026) disappeared when further controlling for age, educational level, and sex. CONCLUSIONS: In patients with stable MS at less advanced disease stages, sNfL did not convincingly relate to cognitive performance, fatigue, depression, or anxiety and thus may not serve as a surrogate biomarker for neuropsychological status in such populations.

Characterizing cognitive deficits and potential predictors in multiple sclerosis: A large nationwide study applying Brief International Cognitive Assessment for Multiple Sclerosis in standard clinical care.

With the proposal of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, the need to screen for cognitive deficits within standard clinical care of patients with multiple sclerosis (MS) has been acknowledged. Data regarding how patient characteristics might predict low cognitive performance and therefore require particularly close monitoring is, however, limited so far. We investigated a large, nationwide patient cohort from ambulatory settings, representing the typical distribution of different subtypes, levels of physical disability, and disease durations. Besides cognitive testing with BICAMS, additional sampling of multiple demographics and clinical variables allowed us to characterize general and domain-specific prevalence patterns of cognitive impairment (CI) as well as to delineate which factors are associated with cognitive performance. In a total of 1,094 patients, CI was present in 28% (using a conservative cut-off of the 5th percentile below normative values), with information-processing speed being most frequently affected. Impairment was overall higher in patients with primary progressive (PPMS) and secondary progressive MS than in patients with relapsing-remitting (RR)MS. Regression modelling revealed that disease subtype (i.e., PPMS), long disease duration, high physical disability, unemployment, low educational level, high age, male sex, and the absence of current disease-modifying treatment were important predictors for worse BICAMS' test performance. These results emphasize the importance of continuous cognitive assessment during regular neurological follow-up visits, with a particular focus on patients being identified as high-risk subjects for CI according to the reported factors.

On the validity of single tests, two-test combinations and the full Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in detecting patients with cognitive impairment.

BACKGROUND: The international standard to screen for cognitive impairment in multiple sclerosis (MS) is BICAMS (Brief International Cognitive Assessment for MS). However, with an application time of approximately 20 minutes, the battery might be too time consuming from a pragmatic perspective of a routine examination. OBJECTIVES: To examine the relative sensitivity and specificity of a BICAMS short version and its validity compared to the total battery. METHODS: The German BICAMS version was applied comprising the Symbol Digit Modalities Test (SDMT), the Brief Visuospatial Memory Test-Revised (BVMT-R) and the Rey Auditory Verbal Learning Test (RAVLT; German VLMT). Single tests and two-test combinations were compared regarding conformity with the total battery. RESULTS: Examining 1320 MS patients, the two-test combination of SDMT-BVMT-R was the most sensitive (92.7%) to impairment and showed the strongest agreement with the total battery (κ = 0.95). Performing binary logistic regression analyses, this combination was also validated by its association with employment status. CONCLUSION: Application of the total BICAMS battery should be the goal to strive for. However, in time-restricted clinical settings, the combined application of SDMT and BVMT-R is a recommendable alternative with an application time of 10 minutes, while single tests alone are not sufficiently sensitive.