Laura Mendozzi

Physical rehabilitation has a positive effect on disability in multiple sclerosis patients

Background: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. Objective: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. Methods: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. Results: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). Conclusions: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

Validation of Italian multiple sclerosis quality of life 54 questionnaire

OBJECTIVES Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8.5). Patients’ participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patientsv 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.

Computer-aided retraining of memory and attention in people with multiple sclerosis: A randomized, double-blind controlled trial

CONTEXT Cognitive compromise is one of the main contributing factors to activity and participation restrictions in people with multiple sclerosis (MS). Computer-aided programs are used for retraining memory and attention, but data on the efficacy of these interventions are scarce. OBJECTIVE To assess the efficacy of computer-aided retraining of memory and attention in people with MS impaired in these abilities. DESIGN AND SETTING Randomized, double-blind, controlled trial. PARTICIPANTS Outpatients (n=82) with subjective complaints of poor attention or memory, confirmed by a score <80th percentile in at least two tests of the Brief Repeatable Battery of Neuropsychological Tests (BRBNT). INTERVENTIONS Participants were randomized to two computer-assisted retraining interventions: memory and attention (study arm), and visuo-constructional and visuo-motor coordination (control arm). Both groups received 16 training sessions over 8 weeks. OUTCOME MEASURES Improvement of 20% or more in at least two BRBNT test scores at 8 weeks compared to baseline (primary end point). Changes in depression and health-related quality of life. RESULTS An improvement occurred in 45% of study patients vs. 43% of control patients (odds ratio 1.07, 95% confidence interval 0.44-2.64). The study treatment was better than the control treatment only on the word list generation test (p=0.016). CONCLUSIONS This trial does not support the efficacy of specific memory and attention retraining in MS.

Evaluation and retraining of adults' cognitive impairments : which role for virtual reality technology ?

Immersive virtual reality (IVR) is a technology already developed to assist cognitive psychologists and therapists in their clinical work with brain-damaged patients. The rationale, the software and the hardware of the first application (ARCANA 1) based on affordable technology are discussed here, in order to provide a concrete example of what the authors think may be the role of IVR as a clinical tool. Although prospects are exciting, extensive research is needed to validate this new approach and reveal its limitations and advantages.

Probing Memory and Executive Functions with Virtual Reality: Past and Present Studies

The technology of virtual reality (VR) has been used to develop interactive programs that simulate everyday life environments, where healthy subjects and patients with central nervous system dysfunctions are asked to carry out tasks that probe incidental memory and executive functions. The results of three studies support previous claims that VR-based tests overcome several limitations of traditional paper-and-pencil tests, are at least as sensitive to target cognitive impairments, while providing a richer range of opportunities for measuring behavior. Preliminary analyses also suggest that results of VR-based memory tests are replicable across laboratories and subjects samples and that the technology is well-accepted and tolerated by both healthy and impaired subjects.

Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis.

Abstract.Depression is the commonest psychiatric disturbance in people with multiple sclerosis (MS), with prevalence higher than in the general population and other chronic diseases. However, accurate assessment of depressive symptoms can be biased by somatic symptoms which are part of both MS and depression. We translated and adapted into Italian the Chicago multiscale depression inventory (CMDI) and assessed its acceptability, internal consistency and test-retest reliability in 213 MS outpatients and 213 individually matched healthy controls. The questionnaire was also tested in 32 people with major depression. Acceptability, internal consistency, and test-retest reliability were good overall. We found greater odds for depressive symptoms in people with MS than healthy controls, with highest odds ratio for somatic symptoms (vegetative subscale). The Italian CMDI is characterized by good acceptability, internal consistency, and testretest reliability. These findings support the use of the CMDI in Italian subjects with MS to screen for and follow depressive symptoms.

Comparison of two brief neuropsychological batteries in people with multiple sclerosis

Background: We compared two brief neuropsychological batteries devised to assess people with multiple sclerosis (MS) and used them to assess the relationship between cognitive impairment and clinical characteristics. Methods: We administered either the Brief Repeatable Battery of Neuropsychological Tests (BRBNT) or the Screening Examination for Cognitive Impairment (SEFCI) to 213 consecutive MS outpatients and 213 individually matched controls. Results: Administration times were longer for BRBNT than SEFCI, for MS and controls (p=0.001). People with MS had lower scores in all individual tests than controls (p<0.001, BRBNT and SEFCI). By the criterion of poor performance on one or more tests, the sensitivity of BRBNT was 41.9% and that of SEFCI 31.5%. The corresponding figures by poor performance on two or more tests were 16.2% for BRBNT and 18.5% for SEFCI. The Buschke Selective Reminding and Paced Auditory Serial Addition were the tests best discriminating between people with MS and controls for BRBNT, and the Symbol Digit Modalities test for SEFCI. The only clinical variable independently associated with impaired performance on these batteries was EDSS. Conclusions: Both cognitive batteries were well accepted and easy to administer. Administration time for SEFCI was significantly shorter than for BRBNT; however, alternative forms for serial evaluation are available only for BRBNT. The BRBNT was slightly more sensitive in detecting impairment by the criterion of poor performance on one or more tests. EDSS score was the only clinical variable independently associated with cognitive impairment.

Effects of Bacille Calmette-GuÉrin after the first demyelinating event in the CNS

Objective: To evaluate Bacille Calmette-Guérin (BCG) effects after clinically isolated syndromes (CIS). Methods: In a double-blind, placebo-controlled trial, participants were randomly assigned to receive BCG or placebo and monitored monthly with brain MRI (6 scans). Both groups then entered a preplanned phase with IM interferon-β-1a for 12 months. From month 18 onward, the patients took the disease-modifying therapies (DMTs) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months. Results: Of 82 randomized subjects, 73 completed the study (33 vaccinated and 40 placebo). During the initial 6 months, the number of cumulative lesions was significantly lower in vaccinated people. The relative risks were 0.541 (95% confidence interval [CI] 0.308–0.956; p = 0.03) for gadolinium-enhancing lesions (the primary endpoint), 0.364 (95% CI 0.207–0.639; p = 0.001) for new and enlarging T2-hyperintense lesions, and 0.149 (95% CI 0.046–0.416; p = 0.001) for new T1-hypointense lesions. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18: mean changes from baseline were −0.09 ± 0.72 vs 0.75 ± 1.81 (p = 0.01), 0.0 ± 0.83 vs 0.88 ± 2.21 (p = 0.08), and −0.21 ± 1.03 vs 1.00 ± 2.49 (p = 0.02). After 60 months, the cumulative probability of clinically definite multiple sclerosis was lower in the BCG + DMT arm (hazard ratio = 0.52, 95% CI 0.27–0.99; p < 0.05), and more vaccinated people remained DMT-free (odds ratio = 0.20, 95% CI 0.04–0.93; p = 0.04). Conclusions: Early BCG may benefit CIS and affect its long-term course. Classification of evidence: BCG, as compared to placebo, was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy (Class I evidence).

Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

BackgroundChronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated.MethodWe analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al.ResultsOverall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS.ConclusionThe methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

The application of virtual reality to document coping deficits after a stroke: Report of a case

An immersive virtual reality (IVR) paradigm to assess cognitive flexibility and problem solving was used to document everyday life-coping failures in a patient with cognitive sequelae of an anterior left thalamic stroke. Three years after the ischemie event, the patient was showing clear signs of frontal lobe dysfunction when left unsupervised in real-life settings, yet his performance on traditional neuropsychological tests tapping frontal functions was unremarkable. We speculated, and provided evidence, that his conduct was influenced by the setting and the presence of an examiner who would strengthen his impaired ability to self-generate control over a number of higher order cognitive activities. Thanks to the immersive effect and nonverbal aspects of the interaction provided by IVR, we could document our patients cognitive difficulties on two separate occasions. The reasons why IVR was superior to traditional tests are analyzed with reference to well-known cognitive models of the way frontal networks...