Health-related quality of life as an independent predictor of long-term disability for patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Predictive factors of long-term disability in patients with relapsing-remitting multiple sclerosis (RR-MS) are well known, but the weight of these factors does not explain the entire change of disability. Few studies have examined the predictive value of quality of life (QoL). OBJECTIVES: To determine the value of the initial level of QoL to predict changes in the disability status of patients with MS and to determine if specific-MS questionnaires predict more accuracy in these changes than generic questionnaires. DESIGN: multicenter, multi-regional, and longitudinal study. Main inclusion criteria: patients with RR-MS subtype and an Expanded Disability Status Scale (EDSS) score lower than 7.0. Sociodemographic and clinical data were recorded at baseline. Every 6 months up to month 24, QoL (MusiQoL and SF-36) was recorded. At 24 months, individuals were defined into two 'disability change' groups: the worsened and not worsened patients. RESULTS: Five-hundred and twenty-six patients were enrolled: 386 (83.7%) not worsened and 75 (16.3%) worsened patients at 24 months. The activity of daily living and the relationship with healthcare workers dimensions of MusiQoL questionnaire were independent predictors of change in the EDSS score after 24 months. The physical-functioning dimension of the SF-36 questionnaire predicted independently disability change after 24 months. CONCLUSIONS: Patient-reported baseline QoL levels provide additional prognostic information on MS disability beyond traditional clinical or sociodemographic factors. These findings reinforce the importance of incorporating a patient's evaluation of their own QoL level during patient monitoring and the assessment of treatment effects.

Treadmill exercise in early mutiple sclerosis: a case series study.

AIM: The effect of specific exercise therapy programs on the management of balance and walking disorders in multiple sclerosis (MS) patients have not been fully explained yet. Reproducible measurement systems are especially required to show their efficacy. The aim of the present case series study was to explore the feasibility of an aerobic treadmill rehabilitation protocol (endurance training protocol) and its effects on walking parameters, muscular activity and postural balance. An adequate instrumental measure set was adopted to provide evidence of minimal motor dysfunction, not quantifiable by means of standard clinical examination. METHODS: Three minimally impaired MS patients were enrolled. The patients underwent endurance training on a treadmill for four weeks. Posturographic assessment, energy cost measurement and gait analysis by basography and surface electromyography recordings were used as outcome measures. RESULTS: Energy cost during treadmill walking was generally reduced in the three patients after exercise. Indexes of both sway path and sway area used for postural stability measurement were reduced after exercise in two patients, particularly with eyes closed. Minor changes were observed in gait pattern in terms of foot placement. Muscular activity pattern tended to normalize after training. CONCLUSION: The aerobic treadmill exercise is feasible, safe and it may improve early anomalies of posture and gait in early MS patients. In the context of an impairment oriented rehabilitation approach, the set of instrumental measurements proposed seems to be able to identify subclinical anomalies in a very low degree of functional involvement on an individual basis.

Validation of the Multiple Sclerosis International Quality of Life questionnaire.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 +/- 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS.

Sleep--wake and body core temperature rhythms in multiple sclerosis with fatigue.

OBJECTIVE: To study sleep-wake and body core temperature (BCT) circadian rhythms in patients with multiple sclerosis (MS)-associated with chronic fatigue. METHODS: Six relapsing-remitting MS patients with chronic fatigue underwent 48 consecutive hours polysomnography (PSG) with BCT measurement, followed by a Multiple Sleep Latency Test (MSLT). All patients were relapse- and drug-free. Mood depression, brain and cervical cord enhanced MRI, dynamic spirometry and Fatigue Severity Scale (FSS) were assessed just before PSG. RESULTS: In all patients mood depression was absent and dynamic spirometry normal, but FSS confirmed fatigue. MRI showed non-enhancing lesions. Nocturnal sleep was characterized by normal architecture and mean sleep efficiency was only slightly reduced. Arousal index was normal and periodic limb movements during sleep (PLMS) were present in four patients, with an increased index (PLMS-I) in only two of them. Upon MSLT, mean sleep latency was normal in all patients with one sleep onset REM period in one patient. All patients displayed a normal BCT 24-h rhythm. Mesor, amplitude and acrophase of BCT rhythm did not show significant differences between MS and controls. CONCLUSIONS: We found substantially normal sleep-wake and BCT rhythmicity in six patients with MS and fatigue. Non-restorative sleep and abnormal BCT regulation were unlikely mechanisms of chronic fatigue in our MS patients. SIGNIFICANCE: Subjective fatigue and abnormal sleep and BCT can be independent manifestation in MS patients. The findings support the notion that objective measures of fatigue comparable to the MSLT for sleepiness do not exist.

Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment.

Matrix metalloproteinase-9 (MMP-9) is involved in blood-brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNbeta-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNbeta-1a. Twenty-one relapsing-remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNbeta-1a (Rebif 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P < 0.0001), as well as the numbers of 'active' lesions (P ranging from 0.0004 to 0.005) decreased during treatment Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate = 0.85; P < 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TMIP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS.

Hypertension, hyperekplexia, and pyramidal paresis due to vascular compression of the medulla.

MRI showed impingement of the vertebral artery on the left lateral medulla in two patients with arterial hypertension, exaggerated startle reflexes (hyperekplexia), and progressive spastic paresis. One patient underwent microvascular decompression with normalization of arterial hypertension, disappearance of hyperekplexia, and improvement of spastic paresis. The combination of arterial hypertension, hyperekplexia, and progressive spastic paresis should arouse suspicion of neurovascular compression of the lateral medulla.

Cognitive function and quality of life in multiple sclerosis patients.

This is a study on the longitudinal evaluation of cognitive functions in multiple sclerosis (MS) patients and their quality of life (QoL). The study follow-up lasted for 3 years and the evaluation was performed every 9 months for four times altogether. We present data on the first and second session, when we evaluated the frontal component of cognitive functions, behavioural memory and quality of life. We administered the Luria Frontal Lobe Syndrome test (LFLS), the Rivermead Behavioural Memory Test (RBMT), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), SF-36 for QoL evaluation. The frontal component of cognitive functions and behavioural memory involvement is related to a worsening of QoL, in particular in the Physical Functioning and the Mental Health of SF-36.