Quality of life in multiple sclerosis: the impact of depression, fatigue and disability.

This study deals with the assessment of quality of life and its main clinical and demographical determinants in a clinical series of 103 patients with multiple sclerosis (MS) (37 men; 66 women; mean age 44.89 years; mean disease duration 12.40 years; mean EDSS score 4.07). We used the MSQOL-54 inventory, a disease-specific instrument recently validated in an Italian population. Each patient underwent a complete clinical assessment, including that of disability status (Expanded Disability Status Scale), cognitive function (Mini Mental State Examination), depression (Hamilton Rating Scale for Depression) and fatigue (Fatigue Severity Scale). In terms of Pearson's correlations, there was a moderate inverse relationship between disability level and the MSQOL-54 physical composite score, and a moderate to strong inverse correlation between depression or fatigue severity and both the physical and mental composite scores. In a stepwise linear regression analysis, depression, fatigue and disability level were confirmed to be significant and independent predictors of quality of life. Quality of life instruments can help to provide a broader measure of the disease impact and to develop a care program tailored to the patient's needs.

Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years.

OBJECTIVE: To reassess, in a cohort of patients with early-onset multiple sclerosis, the long-term evolution of cognitive deficits, their relationship to the disease's clinical progression, and their effects on daily life. DESIGN: Ten years after our baseline assessment, we again compared the cognitive performance of patients and control subjects on a neuropsychological test battery. Clinical and demographic correlates of cognitive impairment and their effects on everyday functioning were determined by multiple linear regression analysis. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: Forty-five inpatients and outpatients with multiple sclerosis and 65 demographically matched healthy controls from the original sample. MAIN OUTCOME MEASURES: Mean scores of both groups on the neuropsychological test battery in initial and 2 follow-up evaluations (about 4 and 10 years, respectively); number of cognitively impaired subjects, defined by the number of subtests failed; regression coefficients measuring the relationship between clinical variables and cognitive outcome and between mental decline and everyday functioning assessed by the Environmental and the Incapacity Status Scales. RESULTS: Previously detected cognitive defects in verbal memory, abstract reasoning, and linguistic processes were confirmed on the third testing, at which time deficits in attention/short-term spatial memory also emerged. Only 20 of 37 patients who were cognitively unimpaired on initial testing remained so by the end of the follow-up, when the proportion of subjects who were cognitively impaired reached 56%. Degree of physical disability, progressive disease course, and increasing age predicted the extent of cognitive decline. Disability level and degree of cognitive impairment were independent predictors of a patient's handicap in the workplace and in social settings. CONCLUSIONS: In the course of a sufficiently long follow-up, cognitive dysfunction is likely to emerge and progress in a sizable proportion of patients. As multiple sclerosis advances, neurological and cognitive involvement tend to converge. Limitations in a patient's work and social activities are correlated with the extent of cognitive decline, independent of degree of physical disability.

A prospective study on the prognosis of multiple sclerosis.

Two hundred and twenty-four patients at their first diagnosis of multiple sclerosis (MS) were prospectively followed for a mean period of 9.78 years. We considered as endpoints the time to reach non-reversible disability levels corresponding to EDSS scores of 4.0 and 6.0, and the beginning of a secondary progressive phase in the relapsing-remitting subgroup of patients. An initially progressive course and higher basal EDSS scores proved to be the best predictors of unfavorable prognosis. A greater number of functional systems involved at onset as well as higher residual deficits in pyramidal, visual, sphincteric and cerebellar systems were other factors predictive of a poor outcome, whereas sensory system involvement turned out to be favorable. A longer first inter-attack interval was associated with a better prognosis. However, overall number of relapses in the first two years of the disease was of no prognostic value. The presence of oligoclonal banding in the cerebrospinal fluid and a cerebral MRI exam strongly suggestive or suggestive of MS in the early phases of the disease were associated with a higher probability of a worse outcome.

A prospective study on the natural history of multiple sclerosis: clues to the conduct and interpretation of clinical trials.

The study's objectives were to assess the predictive significance of different sets of demographic, clinical and extraclinical variables in identifying multiple sclerosis patients with various risk levels of worsening during the follow-up, in order to provide clues to inclusion criteria and selection of primary clinical end-points in therapeutic trials. Two hundred and twenty-four patients at their first diagnosis of multiple sclerosis admitted to our Department between 1983 and 1990 were prospectively followed-up until the end of 1996. We considered as end-points time to reach non-reversible disability levels corresponding to EDSS scores of 4.0 and 6.0 and the beginning of a secondary progressive phase in the relapsing-remitting subgroup of patients. For the statistical treatment of our data we used the Kaplan-Meier survival curves and the Cox regression analysis. An initially progressive course and higher basal EDSS scores proved to be the best predictors of unfavorable prognosis; a greater number of functional systems involved at onset as well as higher residual deficits in pyramidal, visual, sphincteric and cerebellar systems were other factors predictive of a poor outcome, whereas sensory system involvement turned out to be favorable. In the relapsing-remitting subgroup, a longer first inter-attack interval was associated with a better prognosis; however, overall number of relapses in the first two years of the disease was of no prognostic value. The presence of oligoclonal banding in the cerebrospinal fluid and a cerebral MRI 'strongly suggestive' or 'suggestive' of MS in the early phases of the disease were associated with a higher probability of a worse outcome.

Quantification of impairment in MS: discussion of the scales in use.

Accurate, efficient measurement of disease status has become a key issue in MS clinical practice and research. Despite some perceived problems, the Expanded Disability Status Scale (EDSS) remains the most widely used comprehensive measure of impairment. There is also a place for more restricted scales of impairment which focus on some aspects of neurological function in more detail than the EDSS e.g. measures of ambulation, arm function and cognitive function. Improvements in scales of impairment in the future is likely to result from the use of more quantitative tests of selected components of the neurological examination.

Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year follow-up.

OBJECTIVES: To assess the evolution of cognitive dysfunction in early-onset multiple sclerosis, to identify clinical predictors of mental decline, and to determine its impact on a patient's everyday life. DESIGN: The cognitive performance of 50 patients with multiple sclerosis on a neuropsychological battery was compared with that of 70 control subjects initially and again after a 4-year interval. Clinical predictors of cognitive impairment and its effect on daily life were analyzed by stepwise linear regression. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: A consecutive sample of 50 inpatients and outpatients with multiple sclerosis (mean disease duration, 1.58 years) and 70 demographically matched healthy control subjects selected from the patients' relatives and friends. MAIN OUTCOME MEASURES: Mean psychometric test scores of both groups at the initial and follow-up testing. Regression coefficients measuring the relationship between clinical parameters and cognitive capacity and between mental decline and performance of common tasks measured by the Environmental and the Incapacity Status scales. RESULTS: Multiple sclerosis-related deficits in verbal memory and abstract reasoning on initial testing remained more or less stable on the retest, at which time linguistic disturbances on the Set and Token tests also emerged. A patient's initial disability level predicted decreased performance on only four of 13 cognitive variables, and disease duration did so on only two. Extent of intellectual decline on initial testing, initial disability level, and progressive course were independent determinants of handicap in a patient's work and social activities. CONCLUSIONS: Cognitive and neurological deficits appear not to develop in parallel. Yet cognitive dysfunction proves to be a predictor of handicap in everyday life, even in patients in the incipient phase of multiple sclerosis.

Long-term safety of azathioprine therapy in multiple sclerosis.

We compared the frequency of malignancies in 207 multiple sclerosis patients (mean age 35.75 years, SD 10.60) who took 2.0 mg/kg azathioprine daily (mean duration 4.16 years; SD 2.38) and in 247 nontreated patients (mean age 35.44 years; SD 11.94). Five malignancies were diagnosed in the azathioprine group compared with seven in the control group. The age-adjusted occurrence rate was 3.62/1,000 person-years (95% CI, 1.17 to 8.43) in the treated and 4.24/1,000 person-years (95% CI, 1.70 to 8.73) in the nontreated group; the age-adjusted relative risk of developing a tumor was 0.85.