The clinical value of the patient-reported multiple sclerosis neuropsychological screening questionnaire.

BACKGROUND: Cognitive problems are difficult to identify in patients with multiple sclerosis (MS). OBJECTIVE: To investigate the clinical applicability of the patient-reported MS Neuropsychological Screening Questionnaire (MSNQ-P). METHODS: Cut-off scores were determined to differentiate between cognitively impaired (n = 90), mildly cognitively impaired (n = 115), and cognitively preserved (n = 147) MS patients using receiver operating characteristic analyses. RESULTS: We could not define specific and sensitive cut-off scores. Higher scores (≥27) did indicate cognitive impairment. Among patients with a higher education, lower scores (<12) indicated intact cognition. CONCLUSION: Certain scores can indicate intact or impaired cognitive function. Still, MSNQ-P scores should be interpreted with caution.

Toward the use of proxy reports for estimating long-term patient-reported outcomes in multiple sclerosis.

BACKGROUND: Assessment of disease impact in multiple sclerosis (MS) is usually driven by information obtained directly from patients using patient-reported outcomes. However, when patients' response in longitudinal studies is less reliable or missing, proxy respondents may be used. OBJECTIVE: The objective of this paper is to evaluate whether long-term patient scores can be reliably estimated using scores obtained from proxies. METHODS: Baseline, six-month and two-year data were collected from 155 patients and proxies on the physical scale of the Multiple Sclerosis Impact Scale (MSIS-29). Linear regression analyses were performed with the patient two-year scores as outcome, proxy two-year scores as predictor and other variables that could contribute to a better prediction of the patient follow-up score. RESULTS: The patient follow-up score could be predicted rather accurately (R(2) = 0.74) using the patient baseline score and the proxy follow-up score. The correlation between observed and predicted scores was 0.86. The model performed well in different follow-up durations and even better in an external cohort. CONCLUSION: A simple model of a constant value (intercept), the patient baseline score and the proxy follow-up score can predict patients' follow-up score on the physical impact of MS.

Comparing long-term results of PASAT and SDMT scores in relation to neuropsychological testing in multiple sclerosis.

BACKGROUND AND OBJECTIVES: The Symbol Digit Modalities Test (SDMT) shows advantages over the Paced Auditory Serial Addition Test (PASAT) as a cognitive test in patients with multiple sclerosis (MS). To determine which of these tests is most valid and reliable over time as an indicator of the cognitive state of MS patients, long-term test results of both tests were compared in relation to scores of the Brief Repeatable Battery of Neuropsychological tests (BRBN). METHODS: For 485 MS patients visiting the VU University Medical Center Amsterdam for different research projects, a total number of 1078 visits with BRBN (including PASAT and SDMT) was planned. Observed and model-based correlations were used to calculate the construct validity of the SDMT and PASAT 3 seconds test (PASAT3) by comparing correlations with the BRBN-sumscore. The test-retest reliability of each test was also computed. RESULTS: For the construct validity, higher correlations were found between SDMT and BRBN compared to PASAT3 and BRBN, especially for the model-based correlations at baseline. The reliability of the measurements was good for all instruments, with the highest coefficients for the SDMT. CONCLUSION: As a single assessment tool for cognition in MS, the SDMT is more valid and reliable compared to PASAT3.

Do patient and proxy agree? Long-term changes in multiple sclerosis physical impact and walking ability on patient-reported outcome scales.

BACKGROUND: Patient-reported outcome scales (PROs) are useful in monitoring changes in multiple sclerosis (MS) over time. Although these scales are reliable and valid measures in longitudinal studies in MS patients, it is unknown what the impact is when obtaining longitudinal data from proxies. OBJECTIVE: The objective of this paper is to compare longitudinal changes in patient and proxy responses on PROs assessing physical impact of MS and walking ability. METHODS: In a prospective observational study, data on the Multiple Sclerosis Impact Scale (MSIS-29 physical) and Multiple Sclerosis Walking Scale (MSWS-12) were obtained from 137 patient-proxy couples at baseline and at two-year follow-up. Demographic and disease-related variables explaining agreement or disagreement between patients and proxies were investigated using linear regression analyses. RESULTS: Full agreement was found in 56% (MSIS) and 62% (MSWS) of the patient-proxy couples. Complete disagreement was very rare for both scales (2% MSIS, 5% MSWS). When patients were more positive than proxies, a higher age, longer disease duration, longer patient-proxy relationship and increased levels of depression, anxiety and caregiver burden in proxies were observed. CONCLUSION: In the majority of the patient-proxy couples there was agreement. Proxies can serve as a valuable source of information, but caution remains essential when using scores from proxies.

The Arm Function in Multiple Sclerosis Questionnaire (AMSQ): development and validation of a new tool using IRT methods.

PURPOSE: We developed the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) to measure arm and hand function in MS, based on existing scales. We aimed at developing a unidimensional scale containing enough items to be used as an itembank. In this study, we investigated reliability and differential item functioning of the Dutch version. METHOD: Patients were recruited from two MS Centers and a Dutch website for MS patients. We performed item factor analysis on the polychoric correlation matrix, using multiple fit-indices to investigate model fit. The graded response model, an item response theory model, was used to investigate item goodness-of-fit, reliability of the estimated trait levels (θ), differential item functioning, and total information. Differential item functioning was investigated for type of MS, gender, administration version, and test length. RESULTS: Factor analysis results suggested one factor. All items showed p-values of the item goodness-of-fit statistic above 0.0016. The reliability was 0.95, and no items showed differential item functioning on any of the investigated variables. CONCLUSION: AMSQ is a unidimensional 31-item questionnaire for measuring arm function in MS. Because of a well fit in a graded response model, it is suitable for further development as a computer adaptive test. Implications for Rehabilitation A new questionnaire for arm and hand function recommended in people with multiple sclerosis (AMSQ). Scale characteristics make the questionnaire suitable for use in clinical practice and research. Good reliability. Further development as a computer adaptive test to reduce burden of (repetitive) testing in patients is feasible.

Analyzing differences between patient and proxy on Patient Reported Outcomes in multiple sclerosis.

BACKGROUND: Proxy respondents, partners of multiple sclerosis (MS) patients, can provide valuable information on the MS patients' disease. In an earlier publication we found relatively good agreement on patient reported outcomes (PROs) measuring physical impact and functioning, but we found large differences on (neuro)psychological scales. OBJECTIVE: We aim to identify patient and proxy related variables explaining differences between patients' and proxies' ratings on five PROs. METHODS: We report on data from 175 MS patients and proxy respondents. Regression analyses were performed, using as dependent variable the mean differences on five scales: Physical and Psychological scale of the Multiple Sclerosis Impact Scale (MSIS-29), the Multiple Sclerosis Walking Scale (MSWS), Guy's Neurological Disability Scale (GNDS) and the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ). The independent variables were patient, proxy and disease related variables. RESULTS: Caregiver strain was significantly related to differences between patient and proxy scores for all five PROs. A higher level of patient anxiety on the HADS was linked to larger differences on all PROs except the GNDS. In addition, cognitive functioning, proxy depression, walking ability, proxy gender and MS related disability were contributing to the discrepancies. CONCLUSION: We found several patient and proxy factors that may contribute to discrepancies between patient and proxy scores on MS PROs. The most important factor is caregiver burden.

Validation and interpretation of the Dutch version of the Multiple Sclerosis Neuropsychological Screening Questionnaire.

BACKGROUND: The Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) was developed for screening of MS patients at risk for cognitive impairment with a patient self-report (MSNQ-P) and an informant version (MSNQ-I). The objective of this study was to validate the Dutch versions and determine their interpretability. METHODS: The MSNQ was completed by 121 MS patients and their partners (informants). We investigated the factor structure, internal consistency and construct validity. Interrater reliability between MNSQ-P and MSNQ-I was investigated with the intraclass correlation coefficient (ICC) and Cohen's kappa. For interpretability of both MSNQ versions we calculated sensitivity, specificity and cut-off scores. Receiver operating characteristic (ROC) curves with related area under the curve (AUC) were used to evaluate the added value of combining both versions. RESULTS: We found a unidimensional factor structure. Cronbach's alphas were 0.93 and 0.94 for MSNQ-P and MSNQ-I, respectively. The ICC was 0.59 and kappas were ≤0.50. No cut-off score could be defined for the MSNQ-P because of low sensitivity. For the MSNQ-I, sensitivity was 0.75 and specificity 0.71 (AUC 0.80). The cut-off score was 21. ROC curve analyses showed no added value of the MSNQ-P when used in combination with the MSNQ-I. CONCLUSIONS: The MSNQ-I is preferred over the MSNQ-P to screen MS patients for cognitive impairment.

The physiological variation of the retinal nerve fiber layer thickness and macular volume in humans as assessed by spectral domain-optical coherence tomography.

PURPOSE: With the introduction of spectral domain-optical coherence tomography (SD-OCT), changes in retinal nerve fiber layer (RNFL) thickness and macular volume (MV) can be detected with high precision. The aim of this study was to determine whether there is a physiological quantifiable degree of variation of these structures in humans. METHODS: This study took place during a 10-km charity run at VU University Medical Center Amsterdam. Weight, height, hydration status, RNFL thickness (ring scan, 12° around the optic nerve head), and MV (20° × 20°) were assessed in 69 subjects (44 runners, 25 controls) using SD-OCT with eye-tracking function. The SD-OCT scans were assessed before running (normal status), after running (more dehydrated status), and 1 to 1.5 hours after finishing the run (rehydrated status). Controls were measured at the same time intervals as the runners but did not participate in the running event. Changes over time were assessed by general linear models, correcting for repeated measurements. RESULTS: In runners, a significant increase in both RNFL thickness (94.4 µm [baseline] to 95.2 µm [rehydration], P = 0.04) and MV (288.9 µm [baseline] to 291.0 µm [rehydration], P < 0.001) over time was observed. Controls did not show significant changes over time. Anatomically, the physiological change of RNFL thickness was most marked in the nasal sectors. CONCLUSIONS: This prospective study demonstrated a significant physiological variation of the RNFL thickness and MV at a proportion that, on an individual patient level, may be relevant for longitudinal studies in neurodegenerative diseases.