Fatigue In Multiple Sclerosis

  1. Fatigue in Multiple Sclerosis: relationship to depression, disability, and disease pattern
    Mult Scler 2000 Apr;6(2):131-136

  2. Modalities of Fatigue in Multiple Sclerosis: correlation with clinical and biological factors
    Mult Scler 2000 Apr;6(2):124-130

  3. Fatigue in Multiple Sclerosis and its relationship to Depression and Neurologic Disability
    Mult Scler 2000 Jun;6(3):181-5

  4. Information processing efficiency in Multiple Sclerosis
    J Clin Exp NeuroPsychol 2000 Oct;22(5):686-701

  5. Motor-Evoked Potentials in response to fatiguing grip exercise in Multiple Sclerosis
    Clin NeuroPhysiol 2000 Dec 1;111(12):2188-2195

  6. Post-exercise facilitation and depression of Motor Evoked Potentials to TransCranial Magnetic Stimulation: a study in Multiple Sclerosis
    Clin NeuroPhysiol 2004 Sep;115(9):2128-33


Fatigue In Multiple Sclerosis: Relationship To Depression, Disability, And Disease Pattern

Kroencke DC, Lynch SG, Denney DR
Mult Scler 2000 Apr;6(2):131-136
Univ of Kansas, Dept of Psychology, Lawrence, Kansas, KS 66045, USA
PMID# 10773860

In order to investigate the associations between Fatigue and Depression, Disability, and Disease Subtype, 207 individuals with Clinically Definite Multiple Sclerosis (MS) were administered the Fatigue Severity Scale and the Zung Self-rating Depression Scale during a regular clinic appointment.

Their current level of Disability was established using the Expanded Disability Status Scale.

Fatigue and Depression were highly correlated (r=0.58), even when the Depression measure was corrected for items overlapping with Fatigue and other symptoms or consequences of MS (r=0.44). Fatigue and Disability were also correlated (r=0.33).

Multiple regression revealed that both Depressed Mood and Disability were significant predictors of Fatigue, together accounting for approximately 23% of the variance in patients' self-reported Fatigue.

The combined groups of Primary/Progressive (n=45) and Secondary/Progressive patients (n=25) appeared to have higher Fatigue scores than Relapsing/Remitting patients (n=137).

However, an analysis of covariance revealed that this apparent difference was in fact attributable almost exclusively to differences in Disability among the three subtypes of MS.

Other reports of differences in Fatigue between subtypes of MS should be re-examined in light of this finding.


Modalities Of Fatigue In Multiple Sclerosis: Correlation With Clinical And Biological Factors

Iriarte J, Subira ML, Castro P
Mult Scler 2000 Apr;6(2):124-130
Universidad de Navarra, Clinica Universitaria, Dept of Neurology, Pamplona 31080, Spain
PMID# 10773859

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.


Fatigue in Multiple Sclerosis and its relationship to Depression and Neurologic Disability

Bakshi R, Shaikh ZA, Miletich RS, Czarnecki D, Dmochowski J, Henschel K, Janardhan V, Dubey N, Kinkel PR
Mult Scler 2000 Jun;6(3):181-5
Dent Neurologic Institute, Kaleida Health-Millard Fillmore Hospital, State Univ of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY, USA
PMID# 10871830; UI# 20332497

We studied Multiple Sclerosis Fatigue (MSF) and its relationship to Depression and Disability.

    Seventy-one patients
  • 50 Relapsing/Remitting
  • 21 Secondary/Progressive
    were grouped by Fatigue Severity Scale (FSS) into:
    • MS-Fatigue (MSF) (FSS>/=5; n=46) or
    • MS-NonFatigue (MSNF) (FSS</=4; n=20)

Forty-one patients were grouped into MS-Depression (MSD) (n=15) or MS-NonDepression (MSND) (n=26) by interview.

Higher Expanded Disability Status Scale (EDSS) scores were noted in MSF than MSNF patients (P=0.0003); EDSS scores correlated with FSS scores (rho=0.43, P=0.003).

However, Fatigue was present in 58% (n=29) of Relapsing/Remitting patients and in 52% (n=26) of patients with mild physical disability (EDSS<3.5).

Hamilton/Beck Depression severity scores were higher in MSF than MSNF patients and correlated with FSS scores (P<0.05).

MSD had higher FSS scores than MSND patients (P=0.008). After controlling for EDSS, Depression severity continued to correlate with FSS scores (rho=0.37, P=0.02).

After controlling for Depression, FSS scores no longer correlated with EDSS scores (rho=0.27, P=0.09).

Thus, MSF is independent of physical disability, but is associated with Depression, suggesting that common mechanisms play a role in MSF and MSD including Psychological factors or Brain lesions in specific NeuroAnatomic Pathways.

Further study is warranted to determine if AntiDepressant medications improve Fatigue in MS.


Information Processing Efficiency In MS

Archibald CJ, Fisk JD
J Clin Exp Neuropsychol 2000 Oct;22(5):686-701
Dalhousie University, ALB, Canada
PMID# 11094403; UI# 20547998

Reduced Information Processing Efficiency, consequent to impaired Neural transmission, has been proposed as underlying various Cognitive problems in patients with Multiple Sclerosis (MS).

This study employed two measures developed from Experimental Psychology that control for the potential confound of Perceptual-Motor abnormalities (Salthouse, Babcock, & Shaw, 1991; Sternberg, 1966, 1969) to assess the Speed Of Information Processing and Working Memory Capacity in patients with mild to moderate MS.

Although patients had significantly more Cognitive complaints than Neurologically intact matched controls, their performance on standard tests of Immediate Memory Span did not differ from control participants and their Word List Learning was within normal limits.

On the experimental measures, both Relapsing/Remitting and Secondary/Progressive patients exhibited significantly Slowed Information Processing Speed relative to controls.

However, only the Secondary/Progressive patients had an additional decrement in Working Memory Capacity. Depression, Fatigue, or Neurologic disability did not account for performance differences on these measures.

While Information Processing Speed may be slowed early in the disease process, deficits in Working Memory Capacity may appear only as there is progression of MS.

It is these latter deficits, however, that may underlie the impairment of new learning that patients with MS demonstrate.


Motor-Evoked Potentials In Response To Fatiguing Grip Exercise In Multiple Sclerosis

Petajan JH, White AT
Clin NeuroPhysiol 2000 Dec 1;111(12):2188-2195
Univ of Utah School of Medicine, Dept of Neurology, UT, Salt Lake City, USA
PMID# 11090771; UI# 20546066

This study examined Central and Peripheral effects of fatiguing exercise (3 min maximal grip) in healthy controls (n=10) and Multiple Sclerosis (MS) subjects with Weakness, MS-W (n=16) and Normal Motor function, MS-NM (n=16) in the studied extremity.

TransCranial Magnetic Stimulation (TMS) was used to assess resting and facilitated Motor-Evoked Potentials (MEPs) of Abductor Pollicus Brevis (APB) and Flexor Carpi Radialis (FCR) muscles before and after fatiguing exercise.

Exercise-induced depletion and recovery of PhosphoCreatine (PCr) were measured using (31)P Magnetic Resonance Spectroscopy ((31)PMRS) in FCR.

Results and Conclusion
MS subjects demonstrated significantly lower peak force and a faster decline in force than controls.

ContraLateral muscle activation (hand grip) before the fatigue protocol resulted in significantly increased MEP amplitudes in all groups.

ContraLateral hand grip following fatiguing exercise resulted in significantly higher MEP amplitudes in controls and MS-NM subjects, but not MS-W subjects.

Fatiguing exercise resulted in prolonged Central Motor Conduction Time (CMCT) in MS subjects, but not controls. No group differences in PCr depletion or resynthesis were observed.

All groups demonstrated significant Post-Exercise Depression (PED) of MEP amplitude that persisted beyond the time course of PCr recovery, indicating Fatigue was Central in origin.

MS subjects were less able than controls to increase Cortical excitability using ContraLateral muscle activation following fatiguing exercise, possibly indicating impaired conduction in the Corpus Callosum.


Post-Exercise Facilitation And Depression Of Motor Evoked Potentials To TransCranial Magnetic Stimulation: A Study In Multiple Sclerosis

Perretti A, Balbi P, Orefice G, Trojano L, Marcantonio L, Brescia-Morra V, Ascione S, Manganelli F, Conte G, Santoro L
Clin NeuroPhysiol 2004 Sep;115(9):2128-33
University of Naples Federico II, Department of Neurological Sciences, Servizio di Neurofisiopatologia, Via Sergio Pansini 5, 80131 Naples, Italy
PMID# 15294215

To evaluate Motor Cortex excitability changes by Transcranial Magnetic Stimulation (TMS) following repetitive muscle contractions in patients with Multiple Sclerosis (MS); to state whether a typical pattern of post-exercise Motor Evoked Potentials (MEPs) is related to clinical Fatigue in MS.

In 41 patients with definite MS (32 with Fatigue and 9 without Fatigue according to Fatigue Severity Scale) and 13 controls, MEPs were recorded at rest: at baseline condition, following repetitive contractions until Fatigue, and after Fatigue, to evaluate Post-Exercise MEP Facilitation (PEF) and Depression (PED).

After exercise, MEP amplitude significantly increased both in patients and controls (PEF). When Fatigue set in, MEP amplitude was significantly reduced in normal subjects (PED), but not in patients.

Post-exercise MEP findings were similar both in patients with and without Fatigue.

Our findings suggest an IntraCortical motor dysfunction following a voluntary contraction in MS patients, possibly due to failure of depression of facilitatory Cortical circuits, or alternatively of inhibitory mechanisms.

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