A comparison of the brief international cognitive assessment for multiple sclerosis and the brief repeatable battery in multiple sclerosis patients.

BACKGROUND: Recently, a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been developed as an international and standardized brief cognitive test, which is easily performed in everyday clinical practice for neuropsychological assessment in multiple sclerosis (MS). However, we need to gather more information about this tool compared to other neuropsychological batteries. The aim of our study is to compare the performance of BICAMS and Brief Repeatable Battery (BRB) in MS subjects. METHODS: Tests of the BRB and BICAMS were administered to MS patients recruited from 11 Italian MS centres. Cognitive impairment (CI) was defined as the failure on at least two tests (scores below the fifth percentile) on the BRB and as the failure on at least one test of the BICAMS. The agreement between the performances on the two batteries was assessed through Cohen's K statistic. Finally we calculated the effects sizes for each test of the two batteries using Cohen's d. RESULTS: The two batteries were administered to 192 MS patients (142 women, 50 men; mean age 41.4 ± 10.8 years, mean education 12.3 ± 3.5 years). Mean scores of patients were lower compared to those of healthy subjects in all the cognitive measures examined. Forty-six MS patients were identified as impaired and 48 as unimpaired on both of the batteries, when the Symbol Digit Modalities Test (SDMT) was included in the analysis. Cohen's K statistic was 0.46 which corresponds to a moderate accord. If the SDMT was excluded from the BRB, 37 MS patients were identified as impaired and 57 as unimpaired on both of the batteries. Cohen's K statistic was 0.3 which corresponds to a poor accord. The SDMT, the Paced Auditory Serial Addition Test (PASAT) 3 and 2 yielded higher d values (SDMT 0.83, PASAT 3 0.65, PASAT 2 0.84). CONCLUSIONS: This study confirms the feasibility of BICAMS in everyday clinical practice for the identification of CI and highlights the good psychometric properties of the SDMT.

Responsiveness of the Multiple Sclerosis International Quality of Life questionnaire to disability change: a longitudinal study.

BACKGROUND: Responsiveness, defined as the ability to detect a meaningful change, is a core psychometric property of an instrument measuring quality of life (QoL) rarely reported in multiple sclerosis (MS) studies. OBJECTIVE: To assess the responsiveness of the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire to change in disability over 24 months, defined by change in the Expanded Disability Status Scale (EDSS) score. METHODS: Patients with MS were enrolled into a multicenter, longitudinal observational study. QoL was assessed using both the MusiQoL and the 36-Item Short-Form (SF-36) instruments at baseline and every 6 months thereafter up to month 24; neurological assessments, including EDSS score, were performed at each evaluation. RESULTS: The 24-month EDSS was available for 524 patients. In the 107 worsened patients, two specific dimensions of MusiQoL, the sentimental and sexual life and the relationships with health care system dimensions, and 'physical' scores of SF-36 showed responsiveness. CONCLUSIONS: Whereas specific dimensions of MusiQoL identified EDSS changes, the MusiQoL index did not detect disability changes in worsened MS patients in a 24-month observational study. Future responsiveness validation studies should include longer follow-up and more representative samples.

Enhancing cognitive rehabilitation in multiple sclerosis with a disease-specific tool.

PURPOSE: Computerised rehabilitation programs can be used to address cognitive deficits typically caused by multiple sclerosis (MS). However, there are still doubts on their effectiveness, due to mixed results obtained in clinical trials. The objective of this paper is to improve cognitive rehabilitation (CR) practices in MS, by presenting and assessing a MS-specific cognitive rehabilitation software. METHODS: We conducted a detailed analysis of how CR is carried out in practice in MS rehabilitation centres. From the analysis, we elicited a reference CR process, and identified the essential features a software supporting the process should have. We designed and implemented MS-rehab, a novel MS-specific computerised rehabilitation system having the identified features. We experimented MS-rehab in a pilot study involving eight MS patients. To highlight the improvement with respect to the state of the art, we compared MS-rehab with available professional tools selected using well defined criteria. RESULTS: This paper has three main contributions: (1) the identification of a set of essential features a computerised tool for CR in MS should provide; (2) MS-rehab, a novel CR system designed for MS therapists and patients, which embodies innovative MS specific features; (3) the assessment of MS-rehab efficacy in a pilot study with MS patients. CONCLUSIONS: The availability of a MS-specific CR system like MS-rehab fosters the design of more rigorous clinical studies on the effectiveness of computerised rehabilitation in MS. MS-rehab demonstrated its potential and innovativeness as a tool for cognitive rehabilitation in MS.IMPLICATIONS FOR REHABILITATIONComputerized tools for cognitive rehabilitation (CR) in multiple sclerosis (MS) can be improved by a set of MS-specific features.The availability of advanced home-based cognitive rehabilitation mechanisms is fundamental for supporting standardized cognitive rehabilitation protocols in MS.A MS-specific CR system has given promising results in a pilot study involving MS patients.Hardly do state-of-the-art professional tools include all the required MS specific features.

An expert system for the evaluation of EDSS in multiple sclerosis.

Multiple sclerosis is a disease of unknown aetiology. Despite several advances in therapy in recent years, some problems such as the prognostic criteria are imperfectly understood. Several experimental trials of therapy in multiple sclerosis are in course in order to discover a successful treatment. Most of these research studies use a clinical rating scale named Expanded Disability Status Scale (EDSS) as an evaluation tool for the effects of drugs. This scale is defined by a set of rules written in English which provide a numerical quantification of the neurological examination. Although EDSS has been widely used for almost 20 years, its application still depends on the interpretation of the neurologist who performs the neurological examination, and many applications of the scale performed by different neurologist on the same patient can give different results. This is a serious problem for international trials because they lack of a reliable measure of the effects of drugs. Here, we present an expert system for the automatic evaluation of EDSS in multiple sclerosis, which has been developed to overcome this problem. The expert system exploits an explicit representation of EDSS rules, it is able to explain its conclusions and it provides a revision tool to support the user if no satisfying solution can be reached. Using this expert system, clinical trials based on EDSS can benefit of a more reliable evaluation tool providing more valuable results.

MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients.

Even though anti-interferon beta (IFNß) antibodies are the main determinants of IFNß bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNß biological activity in IFNß-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFNß binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFNß therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFNß bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFNß therapy.

Refining an automatic EDSS scoring expert system for routine clinical use in multiple sclerosis.

The Expanded Disability Status Scale (EDSS) has been the most widely used measure of disability in multiple sclerosis (MS) clinical trials. Although EDSS has the advantage of familiarity with respect to recent proposals, and remains the de facto standard, it is difficult to use consistently between evaluators. Automatic EDSS (AEDSS) is an expert system designed to overcome this problem. It constrains the neurologist to follow precise reasoning steps, enhancing EDSS reliability. In this paper, we show how a deep analysis of the neurological knowledge involved has been essential for adopting AEDSS in routine clinical use. We present an ontology for the EDSS domain and highlight the enhancements to AEDSS due to this additional knowledge. A validation experiment in four MS centers in Italy showed that AEDSS reduces interrater variability, and in many cases, is able to correct errors of neurologists.