Long-term effects of prolonged-release fampridine in cognitive function, fatigue, mood and quality of life of MS patients: The IGNITE study.

BACKGROUND: Studies have reported conflicting results regarding the potential benefit of prolonged release (PR) fampridine in other domains besides walking. Moreover, only a small number of studies have explored long- term effects of PR fampridine. The aim of this study was to assess cognitive function, quality of life, mood and fatigue in MS patients treated with fampridine after 6 and 12 months of treatment. METHODS: IGNITE was an observational, open label study. Subjects were examined with the timed 25-ft walk (T25FW) and the BICAMS battery and were asked to complete the Multiple Sclerosis Impact Scale (MSIS-29), Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory-II (BDI-II) and MS International Quality-of-Life questionnaire (MUSIQOL) at baseline and at weeks 24 and 48. Patients were sub-grouped into responders (n:40) and non-responders (n:20) according to T25FW performance after 2 weeks on treatment. RESULTS: After 6 months, statistically significant improvement was observed on T25FW (p < .001), SDMT (p < .001) and MSIS29 (p < .001), for responders. After 1 year on treatment, statistically significant improvement was observed in T25FW (p < .001), MSIS29 (p = .004), SDMT (p < .001) and MUSIQOL (p = .03) for responders. There were no statistically significant improvements for the non-responders. CONCLUSIONS: PR Fampridine may have a beneficial effect on information processing speed though not on memory. Study data provide some evidence that fampridine treatment may reduce the impact of MS on daily activities and improve quality of life but has no effect on subjective fatigue and mood.

Should whole body cryotherapy sessions be differentiated between women and men? A preliminary study on the role of the body thermal resistance.

The aim of this study was to investigate how body thermal resistance between sexes evolves over time in the recovery period after a WBC session and to show how this parameter should be considered as a key parameter in WBC protocols. Eighteen healthy participants volunteered for the study (10 males and 8 females). Temperature (core and skin) were recorded pre- and post (immediately and every 5 min until 35 min post) exposure to a single bout of WBC (30 s at -60 °C, 150 s at -110 °C). From both core and skin temperatures a bio-heat transfer model was applied which led to the analytical formulation of the body thermal resistance. An unsteady behavior presenting a similar time-evolution trend in the body insulative response is shown for both females and males, possibly due to the vasodilatation process following an intense peripheral vasoconstriction during the extreme cold. Females present a 37% higher inner thermal resistance than males when reaching an asymptotical thermal state at rest due to a higher concentration of body fat percentage. Adiposity of tissues inherent in fat mass percentage appears to be a key parameter in the body thermal resistance to be taken into account in the definition of appropriate protocols for males and females. The conclusions of this preliminary study suggest that in order to achieve the same skin effects on temperature and consequently to cool efficiency tissues in the same way, the duration of cryotherapy protocols should be shorter when considering female compared to male.

Cognitive impairment among patients with multiple sclerosis: associations with employment and quality of life.

OBJECTIVES: To explore the relationship between cognitive impairment and conventional measures of disability in multiple sclerosis (MS), quality of life (QOL) and employment status using the brief international cognitive assessment for multiple sclerosis (BICAMS) in the routine outpatient clinic. METHODS: 62 patients with MS were assessed on the BICAMS test battery for cognitive impairment. Data were obtained on employment status and a number of questionnaires completed including fatigue severity score, multiple sclerosis neuropsychological questionnaire, hospital anxiety and depression scale, the functional assessment of multiple sclerosis (FAMS) as well as on the EuroQOL five dimension questionnaire (EQ-5D). Other assessments include the patient activation measure and unidimensional self-efficacy scale for multiple sclerosis. RESULTS: Cognitive assessment revealed 44 subjects (65%) had evidence of cognitive impairment on formal testing. In comparison with patients without evidence of cognitive impairment, cognitively impaired patients exhibited significantly higher rates of unemployment (p=0.009). The symbol digits modalities test was the most significant predictor of unemployment. Cognitive impairment was associated with lower QOL scores on the FAMS (p=0.001) and EQ-5D (p<0.001). CONCLUSIONS: BICAMS provides a sensitive and easy to administer screening test for cognitive impairment within the outpatient setting. Cognitive impairment is common in our cohort of patients with MS attending outpatients and appears to be associated with increased rates of unemployment and lower measures of QOL.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in Greek population with multiple sclerosis.

BACKGROUND: Cognitive impairment is experienced by about 50% of patients with Multiple Sclerosis (MS) worldwide and affects their employment, disease management and quality of life in general. The Brief International Cognitive assessment for MS (BICAMS) is a brief, practical and potentially universal battery for cognitive impairment in MS patients. It consists of three tests: the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT-2) and the Brief Visuospatial Memory Test-Revised (BVMT-R). OBJECTIVE: The objective of this study was to validate the BICAMS in Greek MS patients and controls. METHODS: Forty four MS patients and seventy nine healthy control (HC) participants were recruited and tested. They were group matched for age, education, gender and also premorbid cognitive reserve. All of them completed the three tests of the BICAMS battery. Instead of CVLT-2, the Greek validated form (Greek Verbal Learning Test, GVLT), was used. In addition, cognitive reserve was assessed using the Cognitive Reserve Index questionnaire (CRIq) standardized for the Greek population. RESULTS: Significant difference was found in the performance of the two groups in all tests (p<0.0001, p<0.02, p<0.009 for SDMT, GVLT and BVMT-R respectively). Test-retest reliability was good for all the tests. Based on the criterion of 1 or more tests below the 5th percentile of healthy controls performance, 47% of patients were found impaired. CONCLUSIONS: The study provides validation of BICAMS in Greek population and therefore facilitates the use of this battery in clinical practice and in future studies of MS patients in Greece.

A Randomised Controlled Trial of Efficacy of Cognitive Rehabilitation in Multiple Sclerosis: A Cognitive, Behavioural, and MRI Study.

Aim. To explore the efficacy of home-based, computerised, cognitive rehabilitation in patients with multiple sclerosis using neuropsychological assessment and advanced structural and functional magnetic resonance imaging (fMRI). Methods. 38 patients with MS and cognitive impairment on the Brief International Cognitive Assessment for MS (BICAMS) were enrolled. Patients were randomised to undergo 45 minutes of computerised cognitive rehabilitation using RehaCom software (n = 19) three times weekly for six weeks or to a control condition (n = 19). Neuropsychological and MRI data were obtained at baseline (time 1), following the 6-week intervention (time 2), and after a further twelve weeks (time 3). Cortical activations were explored using fMRI and microstructural changes were explored using quantitative magnetisation transfer (QMT) imaging. Results. The treatment group showed a greater improvement in SDMT gain scores between baseline and time 2 compared to the control group (p = 0.005). The treatment group exhibited increased activation in the bilateral prefrontal cortex and right temporoparietal regions relative to control group at time 3 (p < 0.05FWE corrected). No significant changes were observed on QMT. Conclusion. This study supports the hypothesis that home-based, computerised, cognitive rehabilitation may be effective in improving cognitive performance in patients with MS. Clinical trials registration is ISRCTN54901925.

A preliminary validation of the brief international cognitive assessment for multiple sclerosis (BICAMS) tool in an Irish population with multiple sclerosis (MS).

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS) irrespective of disease stage or subtype. It is typically underreported and neuropsychological testing can be required to detect more subtle evidence of cognitive impairment. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) was an initiative undertaken by a panel of experts with the primary objective of identifying a brief cognitive assessment tool that could be administered by healthcare professionals without formal neuropsychological training to identify early or subtle cognitive impairment among MS patients. OBJECTIVES: To validate BICAMS in Irish patients with MS and healthy controls. METHODS: Consecutive patients attending the MS outpatient department from January to April 2014 were recruited. Age, gender, education, handedness, MS subtype, expanded disability status scale (EDSS) and disease duration were recorded. They were administered BICAMS composed of Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT-II) and Brief Visuospatial Memory Test (BVMT-R). Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). Control participants were composed of unaffected relatives, spouses or carers attending the clinic with a patient and were matched by age, gender and years of education. Impairment on individual tests was defined as -1.5 SD below reference group means. RESULTS: 67 patients [73% women; mean age: 43.9 yrs (12.1); mean years of education: 13.6 yrs (2.7)] and 66 controls [68% women; mean age 42.7 yrs (12.7); mean years of education: 14.1 yrs (3.2)] were recruited. Of the MS patient group: 70% were classified as having relapsing remitting MS, 28% secondary progressive MS and 2% primary progressive MS (PPMS). Mean EDSS scores were 1.8 (SD: 0.9), 5.7 (SD: 1.4) and 7.0 in each group respectively with mean disease duration of 10.2 (SD: 8.4) years, 20.6 (10.2) and 17 years. Mean scores and standard deviations for patients and control participants respectively were 46 (12.9) and 55.9 (10.9), p < 0.001; d = 0.83 for SDMT; 45.3 (10.2) and 52.8 (8.8), p < 0.001; d = 0.79 for CVLT-II and 17.9 (7.1) and 20.7 (6.6), p = 0.02; d = 0.41 for BVMT-R. Using regression based norms derived from the control sample only 43% of patients compared to 83% of control participants' results were within the normal range on all three tests. As expected higher rates of unemployment was seen amongst the patient population compared to control participants. Using the HADS 11 patients were classified as depressed and 13 as suffering from anxiety. Neither, these measures or the level of fatigue as measured by the MFIS was significantly associated with any of the three outcome measures (Pearson r < ± 0.3). CONCLUSIONS: This study demonstrates that BICAMS is an easy test to administer and should be used as a basic tool to identify patients with cognitive impairment who may benefit from further neuropsychological assessment. Cognitive impairment can put patients at risk of poor self-management of disease including poor mediation adherence, and negatively impact on employment. Once identified appropriate support and monitoring can be put in place. BICAMS may also be used to help guide treatment decisions and rehabilitation. Further studies will be needed to assess its reliability over time and ability to detect meaningful changes.

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.

Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNß-1b trial.

OBJECTIVE: To examine the effects of interferon beta (IFNß)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. METHODS: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNß-1b 250 µg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. RESULTS: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNß-1b 250 µg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNß-1b 250 µg-treated patients (46.0% among IFNß-1b 50 µg-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. CONCLUSIONS: There was a significant survival advantage in this cohort of patients receiving early IFNß-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNß-1b benefit on all-cause mortality. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that early treatment with IFNß-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis.

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.

Cerebellar information processing in relapsing-remitting multiple sclerosis (RRMS).

Recent research has characterized the anatomical connectivity of the cortico-cerebellar system - a large and important fibre system in the primate brain. Within this system, there are reciprocal projections between the prefrontal cortex and Crus II of the cerebellar cortex, which both play important roles in the acquisition and execution of cognitive skills. Here, we propose that this system also plays a particular role in sustaining skilled cognitive performance in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), in whom advancing neuropathology causes increasingly inefficient information processing. We scanned RRMS patients and closely matched healthy subjects while they performed the Paced Auditory Serial Addition Test (PASAT), a demanding test of information processing speed, and a control task. This enabled us to localize differences between conditions that change as a function of group (group-by-condition interactions). Hemodynamic activity in some patient populations with CNS pathology are not well understood and may be atypical, so we avoided analysis strategies that rely exclusively on models of hemodynamic activity derived from the healthy brain, using instead an approach that combined a 'model-free' analysis technique (Tensor Independent Component Analysis, TICA) that was relatively free of such assumptions, with a post-hoc 'model-based' approach (General Linear Model, GLM). Our results showed group-by-condition interactions in cerebellar cortical Crus II. We suggest that this area may have in role maintaining performance in working memory tasks by compensating for inefficient data transfer associated with white matter lesions in MS.

Cross-sectional study assessing long-term safety of interferon-beta-1b for relapsing-remitting MS.

OBJECTIVE: The 16-Year Long-Term Follow-Up (LTF) to the pivotal interferon-beta-1b (IFNbeta-1b) trial explored clinical, MRI, cognitive, and patient-reported outcomes. Here, we report the safety assessments. METHODS: In the pivotal study, 372 patients were randomized to placebo (n = 123), IFNbeta-1b 50 microg (n = 125), or IFNbeta-1b 250 microg (n = 124) subcutaneously every other day for up to 5 years. Sixteen years later, patients were asked to participate in this cross-sectional follow-up study. No particular therapy was stipulated during follow-up. Adverse events experienced since the pivotal trial were recorded. Neutralizing antibodies (NAbs) to IFNbeta-1b were measured using the myxovirus protein A induction assay. Statistical analyses were descriptive. RESULTS: In total, 88.2% of patients (328/372) were identified. Some centers achieved 100% ascertainment, obviating selection bias. Treatment-related adverse events (e.g., leukopenia and liver and thyroid dysfunction) reported by LTF participants were in keeping with those previously established. Based on a follow-up period that includes 2,000 patient-years of IFNbeta-1b treatment, no new adverse events were observed that were associated with long-term IFNbeta-1b exposure. By LTF, NAbs to IFNbeta-1b disappeared in the majority (76%) of NAb-positive patients. NAb status during the pivotal study appeared to have no impact on long-term clinical and MRI outcomes. There were more deaths among patients assigned to placebo in the pivotal study (20/109 [18.3%]) compared with patients who received IFNbeta-1b 50 microg (9/108 [8.3%]) or IFNbeta-1b 250 microg (6/111 [5.4%]). CONCLUSION: The results from the 16-Year Long-Term Follow-Up study support the long-term safety of interferon-beta-1b therapy in multiple sclerosis. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with relapsing-remitting MS taking IFNbeta-1b 50 microg or 250 microg subcutaneously every other day for up to 5 years, with subsequent unspecified treatment, have fewer deaths after 16 years of follow-up than similar patients on placebo for up to 5 years, with subsequent unspecified treatment (risk difference 11.5%, 95% confidence interval 4-19).

Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial.

BACKGROUND: Evidence for efficacy of disease-modifying drugs in multiple sclerosis (MS) comes from trials of short duration. We report results from a 16 y, retrospective follow-up of the pivotal interferon beta-1b (IFNB-1b) study. METHODS: The 372 trial patients were randomly assigned to placebo (n=123), IFNB-1b 50 microg (n=125) or IFNB-1b 250 microg (n=124) subcutaneously every other day for at least 2 y. Some remained randomised for up to 5 y but, subsequently, patients received treatment according to physicians' discretion. Patients were re-contacted and asked to participate. Efficacy related measures included MRI parameters, relapse rate, the Expanded Disability Status Scale, the Multiple Sclerosis Functional Composite Measure and conversion to secondary progressive MS. RESULTS: Of the 88.2% (328/372) of patients who were identified, 69.9% (260/372) had available case report forms. No differences in outcome between original randomisation groups could be discerned using standard disability and MRI measures. However, mortality rates among patients originally treated with IFNB-1b were lower than in the original placebo group (18.3% (20/109) for placebo versus 8.3% (9/108) for IFNB-1b 50 microg and 5.4% (6/111) for IFNB-1b 250 microg). CONCLUSIONS: The original treatment assignment could not be shown to influence standard assessments of long-term efficacy. On-study behaviour of patients was influenced by factors that could not be controlled with the sacrifice of randomisation and blinding. Mortality was higher in patients originally assigned to placebo than those who had received IFNB-1b 50 microg or 250 microg. The dataset provides important resources to explore early predictors of long-term outcome.

Cerebellar contributions to working memory.

Anatomical studies show the existence of two well-characterized cortico-cerebellar 'loops' that connect prefrontal and cortical motor areas each with their own modules in the cerebellar cortex. The involvement of the cerebellar 'motor' modules in motor skills is well established, but little is understood about the way that cerebellar prefrontal modules process information from the prefrontal cortex. This question is particularly important for understanding the human cortico-cerebellar system because the prefrontal loop appears to have expanded significantly during the course of evolution. Here, we investigate whether cerebellar modules known to be connected with the prefrontal cortex (specifically within cerebellar cortical lobule VII) become engaged by the execution of skilled cognitive operations. We tested the anatomically specific hypothesis that this area would be activated by the skilled maintenance and manipulation of items within verbal working memory. We used the Paced Auditory Serial Addition Test (PASAT) in combination with a sparse sampling method to avoid artefact caused by speech-related head movement on the BOLD timecourse. Consistent with our hypothesis, we report that activity in the experimental condition was evoked in medial portions of cerebellar cortical lobule VII (relative to a closely matched control task). As would be anticipated, the motor demands common to experimental and control tasks activated face areas of the motor cortex as well as connected motor areas of the cerebellar cortex. We discuss this evidence in the context of theories of cortico-cerebellar information processing.

A longitudinal study of cognition in primary progressive multiple sclerosis.

There are few longitudinal studies of cognition in patients with multiple sclerosis, and the results of these studies remain inconclusive. No serial neuropsychological data of an exclusively primary progressive series are available. Cross-sectional analyses have revealed significant correlations between cognition and magnetic resonance imaging (MRI) parameters in primary progressive multiple sclerosis (PPMS). This study investigated cognitive and MRI change in 99 PPMS patients from five European centres for 2 years. They were assessed at 12 month intervals using the Brief Repeatable Battery, a reasoning test, and a measure of depression. The MRI parameters of T1 hypointensity load, T2 lesion load, and partial brain volume were also calculated at each time point. There were no significant differences between the mean cognitive scores of the patients at year 0 and year 2. However, one-third of the patients demonstrated absolute cognitive decline on individual test scores. Results indicated that initial cognitive status on entry into the study was a good predictor of cognitive ability at 2 years. There was only a small number of significant correlations between changes in cognition and changes on MRI, notably T1 hypointensity load with the two attentional tasks (r = -0.266, P = 0.017; r = -0.303, P = 0.012). It is probable that multiple factors underlie this weak relation between the cognitive and MRI measures.

Outcomes and performance of the Tesio twin catheter system placed for hemodialysis access.

PURPOSE: To assess the effectiveness of and outcomes with a twin catheter system. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records, hemodialysis records, and clinical information system data from 132 consecutive patients who were referred for placement of a tunneled catheter for hemodialysis access. A commercially available twin catheter system was placed in all patients. Outcomes evaluated included infection rate, complication rate, and catheter malfunction and failure rates. Performance parameters evaluated included blood flow rates, urea reduction percentages, and recirculation percentages. RESULTS: One hundred eighty-four twin catheter systems were placed in 132 patients from January 11, 1996, to October 23, 1997. The initial technical success rate was 100%. There were four immediate procedural complications: Air emboli occurred in two patients, and prolonged bleeding necessitating intervention occurred in two. The total number of days a catheter was in place was 13,200 (mean, 74.6 days). Thirty-one infections occurred in 20 patients (total infection rate, 0.23 episodes per 100 catheter days). Sixty-five catheters malfunctioned during the study period, 19 of which necessitated removal, for a rate of 0.14 episodes per 100 catheter days. The average blood flow rate was 281.4 mL/min (range, 117.1-405.6 mL/min; median, 295.2 mL/min). Mean and median urea reductions were both 61%. Mean and median recirculation was 6.1% and 3.5%, respectively (range, 0%-31%). CONCLUSION: Percutaneous placement of the tunneled twin catheter system can be performed with excellent technical success and safety and acceptable catheter performance and outcomes for effective intermediate- to long-term hemodialysis.

A new test of memory for multiple sclerosis I: format development and stimuli design.

Memory tests were often developed for healthy populations. The accuracy of these measures is reduced when administered to patients with neurological diseases, who may experience physical and/or cognitive symptoms. Also, methodological factors, for example, spanning the ability spectrum, and content/format artefacts, may contribute to a decline in test precision. The aim of this study was to develop a new test of memory, which addresses these issues. The new memory test comprises assessments of recall, paired association, and recognition, at a Task Familiarisation stage and two difficulty levels, for both the verbal and spatial modalities. It was administered to 85 healthy individuals and 100 patients with multiple sclerosis (MS). All patients were able to attempt each task of the new assessment and there was no influence of visual integrity or manual dexterity on memory test performance, supporting the applicability of the tasks to patients with multiple sclerosis. Both the standardisation and validation samples demonstrated a wide range of scores on each section of the new test suggesting that the measure spanned an acceptably broad range of abilities. It seems probable, therefore, that the new assessment offers a more exact measure of verbal and spatial recall, paired association, and recognition memory.

Evidence-based measurement: which disability scale for neurologic rehabilitation?

OBJECTIVE: To compare the 10-item Barthel Index (BI), 18-item Functional Independence Measure (FIM), and 30-item Functional Independence Measure + Functional Assessment Measure (FIM+FAM) as measures of disability outcomes for neurologic rehabilitation. METHODS: A total of 149 inpatients from two rehabilitation units in South England specializing in neurologic disorders were studied. Traditional psychometric methods were used to evaluate and compare acceptability (score distributions), reliability (internal consistency, intrarater reproducibility), validity (concurrent, convergent and discriminant construct), and responsiveness (standardized response mean). RESULTS: All three rating scales satisfied recommended criteria for reliable and valid measurement of disability, and are acceptable and responsive in this study sample. The FIM and FIM+FAM total scales are psychometrically similar measures of global disability. The BI, FIM, and FIM+FAM motor scales are psychometrically similar measures of physical disability. The FIM and FIM+FAM cognitive scales are psychometrically similar measures of physical disability. CONCLUSIONS: In the sample studied, the BI, FIM, FIM+FAM have similar measurement properties, when examined using traditional psychometric analyses. Although instruments with more items and item response categories generate more qualitative information about an outcome, they may not improve its measurement. Results highlight the importance of using recognized techniques of scale construction to develop health outcome measures.