A random sample of 493 Multiple Sclerosis (MS) patients registered with the Northern California Chapter of the National MS Society was surveyed by mail and subsequently interviewed.

With regard to their MS, life style, diet, medical treatment, family history, and insurance coverage. Of this sample, 168 patients (34%) returned completed questionnaires.

The answers on the questionnaire were entered into a database and scores on the Expanded Disability Status Scale (EDSS), the Neurologic Rating Scale (NRS), the Ambulation Index (AI), and the Mean Disability Scale (MDS) were determined.

From the patient's answers to a portion of the questionnaire using a previously validated conversion program.

This survey population of 168 patients seemed to represent well both the random sample and the frame population from which it was drawn.

Patients commonly experienced symptoms for which there are medical treatments currently available such as Bladder Symptoms, Fatigue, Spasticity, Pain, and Depression.

Surprisingly, however, with the exception of Spasticity, patients were only infrequently treated for these complaints.

In addition, despite the recent approval of the beta-Interferons and Copolymer-I in the treatment of MS, only 74% of the appropriate candidates for such treatment had these options discussed with them and only 45% ever actually received such treatment.

Certain clinical features and dietary habits were strongly associated with both EDSS scores and total disability.

Not unexpectedly, either a progressive disease course or the presence of Neurological dysfunction in any one of a number of Functional Areas (e.g. Bladder, Vision, Cognitive Change, etc.) correlated with higher EDSS scores and greater total disability. Fatigue was also strongly correlated with disability.

Indeed, Fatigue accounted (in whole or in part) for 65% of the disability experienced by patients; an observation which only underscores the fact that fewer than one third of the patients who experience Fatigue have ever been tried on medications.

Interestingly, the only factors associated with lower EDSS scores and less total disability were exercise and alcohol consumption. Such associations from a single survey, however, do not establish causation.

It is the purpose of this study to establish a baseline level of function within this survey population so that future surveys in the same set of individuals can allow a prospective assessment of how health outcome has influenced different aspects of the patient's medical care, lifestyle, and insurance coverage.

The symptom of Fatigue is a frequent complaint in Multiple Sclerosis (MS) patients. Signs of fatigability have been documented in these patients as well.

However, correlation with signs of objective Fatigue had not been clarified in MS.

The aim of this study was to ascertain the existence of muscular Fatigue in Multiple Sclerosis patients, and to find out if there is a correlation between the subjective symptom of Fatigue and muscular Fatigue.

Fifty MS patients and 50 age and sex matched volunteers were studied using isometric and isotonic tests using the dominant hand.

Strength was studied in the baseline condition and also after recovery of either an isotonic (experiment A) or isometric effort (experiment B).

Maximum strength, strength in relationship to weight, slope of Fatigability in 11 consecutive contractions, and strength and duration of a maximum effort were calculated.

Fatigue as a symptom was measured using the Fatigue Severity Scale (FSS) and the Fatigue Descriptive Scale (FDS).

Non-parametric techniques were used for the statistical analysis. Patients with MS had less isometric and isotonic strength, but the recovery was the same as recovery in the control group.

There was a negative linear correlation between the symptom of Fatigue and the baseline strength.

In conclusion, this study supports the existence of signs of muscular Fatigue in MS patients. However, the recovery after exercise is normal.

The correlation between the baseline scores in strength and the symptom of Fatigue suggest that the same cause (probably Pyramidal deficits) may be involved in both of them.

Copyright 1998 Lippincott Williams & Wilkins

Although Fatigue is common among Multiple Sclerosis (MS) patients, evaluation of this symptom is difficult due to the subjectivity and variability of the complaint.

We proposed the Fatigue Descriptive Scale (FDS) as a tool to evaluate the severity and quality of Fatigue in a group of patients suffering from MS.

As a way to demonstrate the usefulness of this scale we applied the FDS in a group of 155 patients (105 women and 50 men) with clinically-definite Multiple Sclerosis, as outlined according to Poser's criteria.

Age was 36.2 +/- 11.1 years (range 12-62) and time of evolution was 8.3 +/- 9.4 years (range 1-44). The Fatigue Severity Scale (FSS) was also used.

Descriptive statistics techniques and techniques for nonparametric distribution (Spearman Rank, Kruskal-Wallis ANOVA) were used.

One hundred and eighteen patients reported Fatigue (73 spontaneously, 45 when questioned). All descriptions of Fatigue were ranked according to FDS categories.

Eighty-five patients defined the symptom as Fatigue with exercise, 26 as Asthenia and seven as the worsening of other symptoms.

Fatigue by itself produced limited or disrupted activity in 78 patients; work-related functions were limited in 48 patients; social relations were limited in 29 patients; and self-care difficult for one patient.

Fifty-six patients suffered Fatigue daily. FDS score was 4.9 +/- 3.9 (range 0-13). FSS was 3.1 +/- 1.7 (range 0.2-6.6). FDS and FSS of Krupp were highly correlated (R = 0.87, p < 0.001).

Therefore, in comparison with other scales, the FDS shows remarkable usefulness in classifying, periodicity, and severity of Fatigue in MS patients.

The high correlation with the FSS implies that it is a valid method to measure the severity of Fatigue, as was demonstrated in our paper proposing the FDS.

The importance of this new scale is its ability to inform the clinicians in a very quick, easy, and at the same time complete way, how severe the Fatigue really is and how it affects the patient.

Objective
To describe the results of a multicenter study that validated two new patient-reported measures of Neurologic Impairment and disability for use in MS clinical research.

Background
Self-reported data can provide a cost-effective means to assess patient functioning, and can be useful for screening patients who require additional evaluation.

Methods
Thirteen MS centers from the United States and Canada implemented a cross-sectional validation study of two new measures of Neurologic function.

The Symptom Inventory is a measure of Neurologic Impairment with six subscales designed to correlate with localization of Brain lesion.

The Performance Scales measure disability in eight domains of function: Mobility, Hand Function, Vision, Fatigue, Cognition, Bladder/Bowel, Sensory, and Spasticity.

Measures given for comparison included a Neurologic Examination (Expanded Disability Status Scale, Ambulation Index, Disease Steps) as well as the patient-reported Health Status Questionnaire and the Quality of Well-being Index.

Participants included 274 MS patients and 296 healthy control subjects who were matched to patients on age, gender, and education.

Results
Both the Symptom Inventory and the Performance Scales showed high test-retest and internal consistency reliability. Correlational analyzes supported the construct validity of both measures.

Discriminant function analysis reduced the Symptom Inventory to 29 items without sacrificing reliability and increased its discriminant validity.

The Performance Scales explained more variance in clinical outcomes and global quality of life than the Symptom Inventory, and there was some evidence that the two measures complemented each other in predicting Quality of Well-being Index scores.

Conclusions
The Symptom Inventory and the Performance Scales are reliable and valid measures.

The cause of Chronic Fatigue Syndrome (CFS) is unknown. With respect to factors perpetuating Fatigue, on the other hand, a model has been postulated in the literature.

In which Behavioral, Cognitive, and Affective factors play a role in perpetuating Fatigue.

In the present study, this hypothesized model was tested on patients with CFS and on Fatigued patients with Multiple Sclerosis (MS).

The model was formulated in terms of cause-and-effect relationships and an integral test of this model was performed by the statistical technique, "structural equation modeling," in 51 patients with Chronic Fatigue Syndrome and 50 patients with Multiple Sclerosis matched for age, gender, and education.

Attributing complaints to a somatic cause produced low levels of physical activity, which in turn had a causal effect on Fatigue severity. Depression had to be deleted from the model.

Sense of control over symptoms and focusing on bodily symptoms each had a direct causal effect on Fatigue. The model showed an excellent fit for CFS patients, but was rejected for MS patients.

Therefore, a new model for MS patients had to be developed in which sense of control had a causal effect on Fatigue.

In the MS model, no causal relationship was found between the physical state as measured by the Expanded Disability Status Score (EDSS) and Fatigue or functional impairment.

The present study shows that Cognitive and Behavioral factors are involved in the persistence of Fatigue. Treatment should be directed at these factors.

The processes involved in the subjective experience of Fatigue in CFS were different from the processes related to Fatigue in MS.

Although Fatigue is a frequent complaint of patients with Multiple Sclerosis (MS), little is known about the origins of Multiple-Sclerosis-associated Fatigue.

Our primary focus was to study if the extent of Cerebral abnormalities, as shown on Magnetic Resonance Imaging (MRI), had any relation with the frequency and intensity of Fatigue complaints of patients with a definite diagnosis of MS.

Fatigue severity was rated by the patients with the use of a 2-week diary and a Fatigue questionnaire, while conventional T1- and T₂-weighted MRI provided several measures for Cerebral abnormalities.

In total, 72% of 45 patients reported to be seriously Fatigued, at least several times a week over the last 3-month period.

Fatigue severity was not related to the total extent of Cerebral abnormalities, or to MRI-based atrophy measures. Regional lesion load did not differ between Fatigued and non-Fatigued subjects.

Although Neurological Disability, as measured by the Expanded Disability Status Scale (EDSS) and Neurological Rating Scale (NRS), did correlate significantly with most MRI measures, it showed no relation with Fatigue severity.

Neurological progression rates and number of exacerbations in the 2-year period prior to assessment were not significantly associated with the Fatigue measures.

Therefore, our findings suggest that differences in levels of self-reported Fatigue in patients with Multiple Sclerosis cannot merely be explained by the degree of clinical disease activity, Neurological disability or the extent of MRI abnormalities.

These results are compared to other research findings and the possible role of alternative factors influencing Fatigue in Multiple Sclerosis are discussed.

Fatigue is a frequent and often severe symptom in Multiple Sclerosis. Pathogenic mechanisms proposed for Fatigue include the release of ProInflammatory Cytokines.

Which is thought to have an important effect on changes in the Blood-Brain Barrier (BBB).

To investigate whether Fatigue is related to BBB disruption we studied 11 Relapsing/Remitting MS patients participating in a multicenter longitudinal study.

Comparing the sensitivity of monthly enhanced Magnetic Resonance Imaging (MRI) after standard-dose and triple-dose injection of Gadolinium-diethylene triaminopentoacetic acid (Gd-DTPA).

Serial Gd-enhanced MRI studies were performed in two separate sessions every 4 weeks for 3 months. An expanded version of the Fatigue Severity Scale, including 29 items, was administered 24 h before each MRI examination.

No relationship was found between the number and volume of Gd-enhancing lesions and Fatigue scores at any monthly examination over the study period.

Furthermore changes in MRI activity were not significantly related to changes in Fatigue scores.

These results were obtained on triple-dose delayed scanning, which is more sensitive than standard-dose scanning in detecting areas of BBB disruption.

Our preliminary results thus do not support the hypothesis of a relationship between BBB alterations and Fatigue severity in Multiple Sclerosis.

Introduction
Fatigue is a common and disabling symptom in Multiple Sclerosis (MS). In this study we evaluated if Fatigue is associated with different demographic and clinical features of MS.

Material
A survey was performed on 507 consecutive patients affected by Clinically Definite MS referred to our center between January 1 and December 31, 1993.

During the examination patients were asked to answer a brief Fatigue questionnaire.

To evaluate the probability of the occurrence of Fatigue in association with several covariant factors.

Age, sex, duration, disease form, disease severity, month of examination, functional sub-systems on the Expanded Disability Status Scale (EDSS), a logistic regression analysis was performed.

Results
We confirmed that Fatigue is common in MS, recorded in 53% of patients.

Patients affected by a more severe disability, by Progressive MS, both Primary and Secondary, with an older age at examination, and assessed during spring, had a significantly higher risk of Fatigue. Sex was not associated with the occurrence of fatigue.

When the single items of EDSS were considered, we found that Fatigue is also associated with the occurrence of Cerebellar, Sphincteric, Pyramidal and sensitive Signs.

But not with BrainStem, Visual and Cognitive Impairment.

Conclusion
Fatigue in MS is more frequent in association with specific clinical features.