Fatigue, depression and disability accumulation in multiple sclerosis: a cross-sectional study

Objective:  To investigate the influence of disability and the speed of disability accumulation on fatigue and depression in a large cohort of patients with multiple sclerosis (MS).
Methods:  A total of 412 patients completed the Fatigue Severity Scale (FSS) and Center for Epidemiological Studies Depression Scale (CESD). The patients were registered at our outpatient department and demographic and disease specific data were compared between patients with and without severe fatigue (FSS ≥ 5.0) and clinically significant depressive symptoms (CESD ≥ 16). We investigated the association of Expanded Disability Status Scale (EDSS) scores, multiple sclerosis severity scores (MSSS) and either CESD scores or FSS-scores with severe fatigue and clinically significant depressive symptoms in a multivariable logistic regression model, with adjustment for possible confounders.
Results:  Only CESD scores were independently associated with severe fatigue. FSS scores and female gender were independently associated with clinically significant depressive symptoms. Neither EDSS nor MSSS scores were independently associated with fatigue or depression.
Conclusion:  In patients with MS, fatigue and depression are strongly associated with each other but not with the degree of disability or the speed of disability accumulation.     

Determination of ventricular diameters in multiple sclerosis patients with transcranial sonography (TCS)

Abstract.Context: Brain atrophy is an indicator of diffuse brain pathology that appears even in the early stages of multiple sclerosis (MS). Magnetic resonance imaging (MRI) techniques used in clinical trials suggest a correlation between ventricular enlargement and axonal pathology and clinical disability in MS.Objective: To evaluate by transcranial sonography (TCS) and MRI ventricular diameters in order to assess prospectively the development of brain atrophy in MS.Setting: MS outpatient clinic of a university hospital.Patients and Methods: 38 MS patients (27 females, 11 males) were followed up for 2 years. Ventricular diameters (third ventricle, right and left lateral ventricle) were determined by TCS at baseline, 12 and 24 months and correlated with clinical disability (Expanded Disability Status Scale, EDSS), and the Multiple Sclerosis Functional Composite Score (MSFC). MRI was performed at study entry and after two years.Main outcome measure: Correlation of ventricular diameters measured by TCS and MRI with assessment of clinical disability in MS patients at baseline and after two years.Results: TCS and MRI measurements especially of third ventricle diameter matched closely at study entry and after two years (r = 0.9; p < 0.0001). At all time points the width of the third ventricle was significantly correlated with clinical disability (EDSS: r = 0.6, p < 0.01; MSFC: r = –0.6, p < 0.02). In the follow-up over 2 years there was an increase of the width of the third ventricle in comparison with study entry (p < 0.002). Increase of third ventricular width at study entry was associated with higher EDSS levels after 2 years (p = 0.01).Conclusion: Assessment of ventricular diameters by TCS is a reliable tool with which to monitor brain atrophy in the longitudinal follow-up of MS patients. Because TCS is a simple, inexpensive, non-invasive and generally available bedside-test it may be used in clinical practice as well as in therapeutic trials to assess brain atrophy.(died unexpectedly 05. 08. 2003)     

Cardiovascular dysfunction in multiple sclerosis

Cardiovascular dysfunction (CD) in multiple sclerosis (MS) is related to involvement of reflex pathways in the brainstem. The battery of CD tests was applied to a group of 40 healthy subjects and 40 patients with MS, divided in 2 subgroups according to the expanded disability status scale (EDSS). The tests included: 1) postural blood pressure changes, 2) postural heart rate changes, 3) heart rate changes on inspiration/forced expiration and 4) ECG R-R interval measurement on the Valsalva maneuver. Both groups were subjected to the functional independence scale (FIM). Imaging studies were reviewed and autonomic dysfunction at other levels was explored. The results showed a statistically significant difference (P < 0.05) in all tests when comparing patients to controls. Tests 1 and 4 had the highest significance, with findings of more severe involvement in patients with a higher EDSS and lower FIM. A correlation was also found between CD and brainstem lesions on MRI (P < 0.01). A significant number of MS patients had evidence of CD. Test 1 may be considered a simple marker, in daily clinical practice, to detect subclinical CD. Subclinical CD is a cause of disability in this group of patients.     

Mastery,functional disability and perceived health status in patients with multiple sclerosis

Background and purpose: Multiple sclerosis (MS) is a chronic disease that is difficult to predict and to cope with. Mastery refers to the extent to which patients see themselves as being in control of the forces that affect their lives. It may play an important role in perceived health status and well‐being. The purpose of this study was to clarify whether mastery is associated with functional disability and perceived health status in MS patients and how such an association might function. Methods: Two hundred and three MS patients completed the Short‐Form‐36 Health Survey as well as the Pearlin–Schooler Mastery Scale. Functional disability was assessed using the Kurtzke Expanded Disability Status Scale. Hierarchical multiple linear regression analyses were performed on the data from two MS age groups: <45 and ≥45 years of age. Results: Functional disability was negatively associated with perceived physical health status in both age groups and with perceived mental health status in younger age group. Mastery was positively associated with perceived health status in older age group. Discussion: The findings confirm that mastery might be helpful for older MS patients. Education strategies for MS patients aimed at personal empowerment for the maintaining of physical and mental well‐being may be important.     

Quality of life in patients with multiple sclerosis: the impact of fatigue and depression

Quality of Life (QOL) is impaired in multiple sclerosis (MS) in part due to physical disability. MS-associated fatigue (MSF) and depression (MSD) are common and treatable features of MS, which could also impact on QOL, independent of physical disability. We prospectively studied 60 consecutive patients with MS. QOL was assessed using Multiple Sclerosis Quality of Life (MSQOL)-54. Group differences in QOL scores were assessed after adjusting for Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS) and Hamilton Depression Inventory scores. MS patients were grouped into relapsing-remitting (RR) or secondary-progressive (SP), MSF (FSS> or =5) or MS-nonfatigue (MSNF) (FSS< or =4), and MSD or MS-nondepression (MSND). After accounting for disability and depression, fatigue was associated with impaired QOL with respect to health perception (p=0.03) and limitations due to physical dysfunction (p=0.008). After accounting for disability and fatigue, depression was associated with lower QOL with respect to health perception (p=0.02), sexual dysfunction (p=0.03), health distress (p=0.03), mental health (p=0.006), overall QOL (p=0.006), emotional dysfunction (p=0.04), and limitations due to emotional dysfunction (p=0.03). This study demonstrates that fatigue and depression are independently associated with impaired QOL in MS, after accounting for physical disability, suggesting that their recognition and treatment can potentially improve QOL.     

The role of disability and depression in cognitive functioning within 2 years after multiple sclerosis diagnosis

OBJECTIVES: To investigate cognitive functioning shortly after multiple sclerosis (MS) diagnosis and to examine the relationship with disability, depression and anxiety. METHODS: Data were available for 101 recently diagnosed MS patients and 117 healthy controls. Neuropsychological and clinical assessment included Rao's Brief Repeatable Battery, Expanded Disability Status Scale (EDSS), and Hospital Anxiety and Depression scale (HADS). RESULTS: Patients had lower scores than controls on timed tasks (Paced Auditory Serial Addition Test (PASAT3, p-value adjusted for age, sex and education = 0.04; PASAT2, p = 0.001), Word List Generation Test (WLG, p = 0.04)). Scores on Symbol Digit Modalities Test (SDMT; p = 0.001), PASAT3 (p = 0.01) and PASAT2 (p < 0.001) showed significant association with EDSS. Patients with EDSS >or= 3.0 had significantly lower scores on Selective Reminding Test (SRTC, p = 0.04), SDMT (p = 0.002), PASAT3 (p = 0.002), PASAT2 (p < 0.001) and WLG (p = 0.01) than controls from the general population. Patients with clinically borderline scores of depression scored lower on SDMT (49.5 versus 57.1, p = 0.06) and PASAT3 (39.8 versus 47.1, p = 0.03). However, after adjustment for EDSS and time since disease onset, these differences were not statistically significant. CONCLUSION: Within two years after diagnosis, patients with MS had lower scores compared to healthy controls on timed tasks, suggesting cognitive slowing in patients with early MS. Cognitive impairment was associated with symptoms of depression, but this association could be explained by differences in disability.     

Evaluation of response of multiple sclerosis (MS) relapse to oral high-dose methylprednisolone: usefulness of MS functional composite and Expanded Disability Status Scale

To compare the usefulness of multiple sclerosis functional composite (MSFC) to the Expanded Disability Status Scale (EDSS) in assessing functional changes related to relapse. A prospective 12-week follow-up study after relapse was conducted among 14 multiple sclerosis (MS) patients treated with oral high-dose (1 g) methylprednisolone for 3 days. MSFC and the EDSS were assessed on day 0, before treatment and, 1, 4 and 12 weeks afterwards. In relapses, EDSS (2.5 ± 1.2 to 3.8 ± 1.0) and z-score of the MSFC (0.15 ± 0.58 to −0.59 ± 0.70) worsened. After 1 week of treatment, the EDSS improved (3.3 ± 1.2; P  =   0.002) while the MSFC did not change significantly. At week 4, EDSS improvement was maximal (2.8 ± 1.3; P  =   0.001). At week 12, EDSS remained stable whereas z-score continued improving (0.26 ± 0.74). z-9peg-hole-test was the most sensitive subtest. There was correlation between baseline values of both scales (−0.620, P  <   0.05) and between changes due to relapse (−0.535, P  <   0.05). 78.5% of patients had improved at week 4 (35.7% at week 1). There were no serious adverse effects. MSFC and the EDSS were sensitive to changes due to relapses, although the dynamics for restoring baseline function were different. Our data support the usefulness of both scales in clinical trials, providing complementary information about outcome of MS patients with relapses.     

The epidemiology of multiple sclerosis in Europe

Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of non-traumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100 000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35–64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100 000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-of-illness studies.     

Associations of the Expanded Disability Status Scale with anxiety and depression in multiple sclerosis outpatients

OBJECTIVES: We evaluated cross-sectionally the associations of depression and anxiety with age, sex, duration of illness, educational level, degree of disability and treatment with interferon-beta in outpatients with relapsing-remitting multiple sclerosis (RRMS) during a clinically stable phase of their illness. MATERIALS AND METHODS: The depression status scored on the Beck Depression Inventory (BDI), the symptoms of anxiety assessed using the State Trait Anxiety Inventory (STAI) and the level of disability measured by the Expanded Disability Status Scale (EDSS) were quantified in 86 consecutive RRMS patients. RESULTS: Linear regression analyses indicated that EDSS was independently (P < 0.001) associated with BDI and STAI and accounted for 15.7% and 18.5% of the variance in BDI and STAI respectively. The former association retained its statistical significance in multiple regression models adjusting for demographic and clinical characteristics. CONCLUSIONS: Disability status is an independent but moderate determinant of depression and anxiety in MS patients.     

Sexual dysfunction in male multiple sclerosis patients in relation to clinical findings

Seventy-seven consecutive male patients with clinically definite or laboratory supported definite multiple sclerosis were submitted to a questionnaire and a clinical interview in order to assess the frequency, the nature of sexual dysfunction and its relationship with clinical findings. Twenty-six patients (35%) complained of erectile dysfunction: the defect was partial and inconstant in 11 patients (14%), complete and fixed in 15 (21%). Six patients complained of premature ejaculation, in three of whom the symptom was already present before the onset of the disease. Taking the series as a whole, sexual life was poor or not satisfying at all in 34 patients. Erectile dysfunction was associated with the presence and severity of bladder dysfunction and with disability. The relationship with sensory impairment of legs was slight, no relationship was found with motor involvement of legs, type of course, age and disease duration.     

Alexithymia in multiple sclerosis: relationship with fatigue and depression

Objective –  The aim of this study was to investigate the prevalence of alexithymia in a sample of patients with multiple sclerosis (MS) and to further evaluate the association between alexithymia and the occurrence of common disabling MS-related symptoms such as fatigue and depression.
Methods –  Fifty-eight relapsing–remitting MS patients treated with interferon (IFN)-beta-1a underwent a complete neurological evaluation, including Expanded Disability Status Scale score assessment. Alexithymia, depressive symptoms and fatigue were assessed using the 20-item Toronto Alexithymia Scale, Beck Depression Inventory and Fatigue Severity Scale.
Results –  Prevalence of alexithymia was 13.8%, with 27.6% of patients presenting borderline alexithymia. Sixty-seven per cent of the patients complained of fatigue while 29.3% of them were depressed. Higher levels of fatigue and depression were found in alexithymic patients when compared with non-alexithymic patients. Results from logistic regressions showed that alexithymia significantly contributes to the severity of fatigue and depression.
Conclusions –  Alexithymia was associated with increased severity of fatigue and depression.     

A multidimensional assessment of multiple sclerosis: relationships between disability domains

OBJECTIVE: To test the feasibility of a multidimensional assessment based on both task-related and self-evaluation questionnaire scores in patients with multiple sclerosis (MS); ii) to correlate the results from selective measures with the severity of illness in terms of the Expanded Disability Status Scale (EDSS) score; iii) to assess the relationships between different domains of MS-related disability and handicap. PATIENTS AND METHODS: Eighty-three MS patients (M/F 31/52; age 43.26 +/- 10.9 years, range 21-72) underwent a standard clinical evaluation of motor abilities (by means of the Rivermead Mobility index, Timed Walking Test, Nine Hole Peg test and Hauser Ambulation Index) and cognitive performances (using Digit Symbol, Buschke-Fuld selective remind test, "FAS"-Word Fluency, Wisconsin Card Sorting test and Block design test). The Beck Depression inventory, MS Specific Fatigue Scale, Functional Assessment of MS and London Handicap Scale were applied to evaluate mood, fatigue, quality of life and handicap, respectively. Minimal Record of Disability measures - MRD (i.e. EDSS, Inability Status Scale and Environmental Status Scale) were also applied to test the criterion validity of the selected disability and handicap scales. The Kruskal-Wallis H-test for independent samples tested differences between subgroups with an increasing EDSS score (<3.5, 3.5-6.0, >6.0). The covariance and redundancy of measures included in the multidimensional assessment were evaluated through Factor Analysis. The Multiple Regression Analysis was used to detect the relative impact of either motor or cognitive disabilities and depression on handicap and quality of life. RESULTS: The multimodal assessment took 70 min on average to be performed, being well accepted by patients. Motor abilities worsened as the EDSS score rose, unlike cognitive performances which proved to be similarly impaired at different severity levels. Measures of fatigue and depression were not related to EDSS values. The chosen measures were assigned by Factor Analysis to 4 domains corresponding to motor performance, executive performance, cognitive abilities and quality of life, respectively. Regression analysis showed how handicap and depression independently affect quality of life. While the handicap score is mostly influenced by motor ability, as measured by the Rivermead Mobility Index, the depression score grows independently of any physical or cognitive disability and seems to be related to fatigue self-assessment scores. CONCLUSIONS: A multidimensional approach to MS patient assessment allows a more detailed and sensitive evaluation of their disability profile and perceived difficulties, leading to a care programme tailored to the patient's needs.     

Oral Dimethyl Fumarate in Children With Multiple Sclerosis: A Dual-Center Study

BackgroundFirst-line injectable therapies for multiple sclerosis in children may be ineffective or not well-tolerated. There is therefore an urgent need to explore oral medications for pediatric multiple sclerosis. We review our dual-center experience with oral dimethyl fumarate.MethodsThis study was a retrospective review of children 18 years of age or less with multiple sclerosis treated with dimethyl fumarate at Yale University and the University of Colorado. Clinical, demographic, and magnetic resonance imaging parameters were analyzed.ResultsWe identified 13 children treated with oral dimethyl fumarate for a median of 15.0 months (range, 1 to 25). Dimethyl fumarate was utilized as first-line therapy in five children (38%). Ten children (77%) tolerated dose escalation to the usual adult dose of 240 mg twice daily. Nine children had ≥12 months of follow-up on treatment. Eight of nine (89%) displayed stabilized or reduced relapse rates and disability scores on treatment. Nine children underwent brain magnetic resonance imaging performed after 12 or more months of therapy. New T2 lesions were observed in three children (33%), one of whom had been nonadherent to treatment. Common side effects included facial flushing (8/13, 62%), gastrointestinal discomfort (7/13, 54%), rash (3/13, 23%), and malaise (2/13, 15%). Three children (23%) discontinued treatment because of side effects. No patients displayed laboratory abnormalities including lymphopenia or abnormal liver transaminases. There were no reported infections.ConclusionsOral dimethyl fumarate appears to be safe and generally well tolerated in children with multiple sclerosis. Formal clinical trials to evaluate efficacy are ongoing.