Fatigue In Multiple Sclerosis

Objective
To determine whether Cognitive Fatigue, defined as a decline in Cognitive performance over a single testing session, could be identified in MS.

Methods
Forty-five individuals with MS and 14 healthy control participants completed a 4-hour session of Cognitive testing.

That involved a baseline NeuroPsychological battery, a continuous effortful Cognitive task (completing mental arithmetic problems administered on a computer).

And a repeat NeuroPsychological battery. Self-report measures of Fatigue and Affect were completed before each step of the testing session.

Results
The pattern of change in Cognitive performances over the testing session significantly differed between the MS and control participants.

Individuals with MS showed declines on measures of verbal memory and conceptual planning, whereas the control participants showed improvement.

Although there were no significant differences between the groups on any of the baseline Cognitive measures, the MS participants performed worse than the control subjects.

On tests of visual memory, verbal memory, and verbal fluency that were repeated following the continuous effortful Cognitive task.

Both MS and control participants reported increased mental and physical Fatigue across the testing session compared with their baseline values.

Conclusion
Individuals with MS show declines in Cognitive performance during a single testing session and fail to show the improvement exemplified by healthy control subjects.

Fatigue is a common symptom in neurology and occurs in the diseases of the Central and Peripheral Nervous System.

In order to understand the mechanism of Fatigue, it is important to distinguish symptoms of Peripheral NeuroMuscular Fatigue from the symptoms of physical and mental Fatigue characteristic of disorders like Parkinson's Disease or Multiple Sclerosis.

We have introduced and defined the concept of Central Fatigue for the latter disorders.

We have further proposed, with supportive NeuroPathological data, that Central Fatigue may occur due to a failure in the integration of the Limbic input and the Motor functions within the Basal Ganglia affecting the Striatal-Thalamic-Frontal Cortical System.

Time-dependent frequency decomposition of fluctuations in CardioVascular signals (Heart Rate [HR], blood pressure, and blood flow) provides noninvasive and quantitative evaluation of Autonomic activity during transient and steady-state conditions.

This method was applied during a change of position from supine to standing in patients with Multiple Sclerosis (MS) who experienced unexplained Fatigue and in age-matched control subjects.

No difference in response to standing, as reflected in the time domain parameters (mean HR, mean blood pressure, and mean blood flow), was observed between patients with MS and control subjects.

Moreover, no difference was observed in very-low-frequency and low-frequency (related to Sympathetic activity) content of HR, blood pressure, blood flow, or high-frequency content of HR (related to ParaSympathetic activity).

The only Spectral estimates that showed a significant difference between groups were the ratio of low-frequency to high-frequency content of HR and low-frequency content of HR normalized to total power.

Both these parameters provide an estimate of the SympathoVagal balance. A significant increase in these two estimates on standing was observed in control subjects only.

Indicating possible impairment of the SympathoVagal balance response to standing in patients with MS who experienced Fatigue.

The authors observed a significant age dependence between close age subgroups, which occurred in the MS group only and was observed in some of the investigated Spectral estimates that reflect Vagal activity.

Therefore, the authors assumed that age-related reduction in Vagal activity occurred earlier in patients with MS who experienced Fatigue.

This reduction could also explain the lack of increase in the SympathoVagal balance on standing. To validate this enhanced age dependence, further investigation should be performed in a larger group of subjects with a wider age range.

Fatigue is a common symptom of Multiple Sclerosis (MS) even in the early phases of the disease, when Neurological disability is usually still not present.

To investigate the PathoPhysiology of Fatigue we compared NeuroPhysiological (Motor Evoked Potentials of the four limbs (MEPs), and Brain Magnetic Resonance Imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) Fatigue.

Fatigue was assessed by an interview and scored by the Fatigue Severity Scale. The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, Pyramidal Functional System (FS) score, and Depression score.

MEPs were abnormal in five patients with Fatigue and in one patient without Fatigue.

A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P< 0.005).

Significantly higher Parietal Lobe (P< 0.05), Internal Capsule (P< 0.05), and PeriVentricular Trigone (P< 0.05) lesion loads were found in patients with Fatigue than in those without.

Our results agree with a Central Nervous System origin of Fatigue in MS patients.

This symptom might be a consequence either of a functional DeAfferentation of the Cortex due to Cortico-SubCortical interconnection damage or of DeMyelination in critical sites of the CNS, such as the CorticoSpinal Tract.

Objectives
To explore Fatigue in Multiple Sclerosis and evaluate the specificity of three fatigue scales in this condition: the Fatigue Severity Scale, the Specific Fatigue Scale and the Fatigue Impact Scale.

Material And Methods
We sent out 60 questionnaires with the three scales and the quality of life scale, the Nottingham Health Profile, to patients with Multiple Sclerosis as clinically defined by Poser's Criteria.

Answers were received to 58 questionnaires and the data correlated by Sperman's correlation and the Student t test, with demographic variables (age, age of onset and sex).

And clinical variables (clinical form, time the disease was present, period of time since the previous episode and Kurtzke scale (EDSS).

Results
Fatigue was present in 78% of the patients.

There was correlation between Fatigue Severity Scale and higher basal EDSS, Pyramidal function, Cerebellar function, the period of time the illness was present and the clinical form.

We found that the Specific Fatigue Scale is independent of EDSS.

The Fatigue Impact Scale was correlated with the EDSS apart from the questions concerning Cognitive function.

Conclusions
Fatigue is a common symptom of Multiple Sclerosis which has an independent effect on Cognitive function.

It is also related to involvement of the Pyramidal and Cerebellar systems, and depends on the degree of disability and time the disease has been present.

The Specific Fatigue Scale is a good tool for exploration of this symptom of Multiple Sclerosis.

In 95 patients with the Remitting/Relapsing form of Multiple Sclerosis we investigated Fatigue. All of them were evaluated with the Fatigue Severity Scale and we found it in 64 patients (67.4%).

Gender, Age, Depression and Fuctional Incapacity was not predictive of Fatigue occurrence, while Anxiety and time of disease seems to be correlated with it.

When we analyzed the Fatigue Severity, a correlation between the Higher basal EDSS and the increasing Fatigue severity was found.

Fatigue is a common and disabiling symptom in Multiple Sclerosis but is poorly understood. Self-report measures are designed to capture the patient's subjective sense of Fatigue.

We applied three scales in 15 patients with MS. Nine of them reported Fatigue. The scores were high in all of these patients.

We conclude that these scales must be used in assemble, to evaluate this symptom. Also, Fatigue a very important symptom in Multiple Sclerosis patients.

Although different factors are probably involved in the Etiology of Fatigue in Multiple Sclerosis patients, no definite mechanism has been proposed.

We have proposed that Fatigue is a complex symptom that includes three clinical different entities (Asthenia, Fatigability and Worsening Of Symptoms with effort).

The goal of this study is to demonstrate if there is a peculiar mechanism for each of the different varieties of fatigue. A control sample of 155 patients (105 women, 50 men) with Clinically Definite MS was studied.

Fatigue was measured using the Fatigue Descriptive Scale (FDS) and the Fatigue Severity Scale (FSS). Treatment, Depression, Anxiety, Sleep and Cellular Immune status were studied too.

Fatigue was a symptom in 118 patients (76.13%); 26 patients (22.03%) described it as Asthenia (Fatigue at rest); 85 patients (72.03%) as Fatigability (Fatigue with exercise), and seven patients (5.9%) as worsening of symptoms.

The severity of Pyramidal involvement was significantly more severe in patients suffering from Fatigue; some Immunological parameters were associated with Fatigue as well.

The discriminant analysis of the data shows that some of the ImmunoActivation parameters are associated with Asthenia (F=21.5, P<0.001), and Pyramidal tract involvement is associated with Fatigability (F=10.5, P<0.001).

Sleep Disorders, Anxiety and Depression were linked with Fatigue in a few patients. No relationship with treatment was proven. In conclusion, Fatigue in MS seems to be a heterogeneous entity.

Asthenia and Fatigability may be different clinical entities. Certain ImmunoActivation parameters correlate with the presence of Asthenia while Pyramidal involvement is associated with Fatigability.

Objective
To investigate differences in performance between people with Multiple Sclerosis (MS) and control subjects on clinical tests of balance.

And to assess performance consistency on balance tests in people with MS from morning to afternoon.

Study Design
Two factor repeated measures design with a two group sample of convenience.

Setting & Subjects
Kingston Centre and the Camberwell Centre of the MS Society of Victoria, Australia. Fourteen people with MS and 14 control subjects matched for age, height, and sex.

Main Outcome Measures
Subjects were measured on their ability to maintain standing balance in steady stance, (feet apart, feet together, stride stance, tandem stance, and single leg stance).

During self-generated perturbations (functional reach, arm raise, and step tests) and in response to an external perturbation.

Participants with MS were also asked to rate their fatigue level in the morning and afternoon.

Results
There were no differences between MS and control groups on the ability to maintain standing balance with feet apart, feet together, or in stride stance.

Participants with MS performed more poorly than control subjects in tandem stance and single leg stance and in the functional reach test, arm raise test, step test, and in response to an external perturbation.

There was little change in balance from morning to afternoon in participants with MS (ICCs (2,1) .70 to .94), despite an increase in self-rated Fatigue (t(14) = -3.14, p = .008).

Conclusion
The ability to maintain balance in standing is a marked problem in people with MS despite the consistency of their performance from morning to afternoon.

Maintenance of health is dependent on numerous regulatory interactions between organ systems.

This review discusses inter-organ communication between the Nervous, Endocrine, and Immune Systems and Environmental and Genetic influences on this NeuroEndocrine Immune circuitry.

Stresses of multiple types, including psychological and exposure to chemicals and infectious agents, may combine to enhance NeuroImmunoToxicology.

Altered Nervous System functions can alter Immunity which could result in exacerbation of infections, Cancers or other Immune associated problems.

Inversely, aberrant Immune System activities could lead to pathologies associated with altered Nervous activities, such as Alzheimer's Disease, Chronic Fatigue, or Multiple Sclerosis.

The Nervous, Endocrine and Immune circuitry is multi-directional, and a Chemical, Physical or Emotional Stress could upset the homeostasis.

Fatigue is an unexplained but common and disabling symptom in MS. We assessed Fatigue in 71 patients with MS and identified MS-Fatigue (MSF) and MS-NonFatigue (MSNF) groups.

Fatigue severity did not correlate with regional or global MRI plaque load or Atrophy assessed by conventional sequences. No significant differences were noted in any MRI measures between MSF and MSNF groups.

We suggest that Brain MRI disease topography or severity does not explain Fatigue in MS and that Fatigue is likely due to mechanisms poorly characterized by conventional MRI.

Comment in: Neurology 2000 Apr 25;54(8):1709-10