Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterised by fatigue and musculosketetal pain, the severity of which is variable. Simple reaction times (SRTs) and movement times (SMTs) are slowed in CFS. Our objective is to correlate the day-to-day changes in symptomatology with any change in SRT, SMT or corticospinal excitability.

Ten CFS patients were tested on two occasions up to two years apart. Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the thenar muscles. Threshold TMS strength to evoke MEPs was measured to index corticospinal excitability. SRTs and SMTs were measured.

The percentage change in both SRTs and SMTs between the two test sessions correlated with the percentage change in corticospinal excitability assessed according to threshold TMS intensity required to produce MEPs. This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of SRTs supports the notion of a deficit in motor preparatory areas of the brain.

 

Source: Davey NJ, Puri BK, Catley M, Main J, Nowicky AV, Zaman R. Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome. Int J Clin Pract. 2003 May;57(4):262-4. http://www.ncbi.nlm.nih.gov/pubmed/12800454

 

Corticospinal inhibition appears normal in patients with chronic fatigue syndrome

Abstract:

The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. Thresholds and latencies of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) are normal but intracortical inhibition has not been investigated.

Eleven patients with CFS were compared with 11 control subjects. Each patient completed a questionnaire using visual analogue indices of pain, fatigue, anxiety and depression. Subjects released a button to initiate simple (SRTs) and choice reaction time (CRTs) tasks; for each task, movement times were measured between release of the initiation button and depression of a second button 15 cm away. Subjects held a 10 % maximum voluntary contraction in the thenar muscles of their dominant hand while TMS was applied to the motor cortex; the duration and extent of inhibition of surface electromyographic (EMG) activity were assessed at stimulus strengths above and below the threshold for MEPs.

Patients had significantly (P < 0.05) higher mean indices of fatigue than of pain, anxiety or depression. Mean (+/- S.E.M.) SRTs (but not CRTs) were longer in patients (309 +/- 45 ms) than in controls (218 +/- 9 ms). Movement times were longer in patients for both SRTs and CRTs. TMS thresholds, expressed as a percentage of the maximum stimulator output, were not significantly (P > 0.05) different in both groups for both MEPs (patients, 34 +/- 3%; controls, 36 +/- 3%) and inhibition of voluntary contraction (patients, 29 +/- 2%; controls, 34 +/- 4%). The duration and extent of inhibition did not differ significantly between groups at any stimulus strength. The pattern of change in duration and extent of inhibition with increasing stimulus intensity was no different in the two groups. The duration and extent of corticospinal inhibition in patients with CFS did not differ from controls, adding further evidence to the notion that the feeling of fatigue and the slowness of movement seen in CFS is not manifest in corticospinal output pathways.

 

Source: Zaman R, Puri BK, Main J, Nowicky AV, Davey NJ. Corticospinal inhibition appears normal in patients with chronic fatigue syndrome. Exp Physiol. 2001 Sep;86(5):547-50. http://www.ncbi.nlm.nih.gov/pubmed/11571481

 

Voluntary motor function in patients with chronic fatigue syndrome

Abstract:

INTRODUCTION: The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. In particular, little is known of the involvement of the motor cortex and corticospinal system.

METHODS: Transcranial magnetic stimulation (TMS) was used to assess corticospinal function in terms of latency and threshold of motor-evoked potentials (MEPs) in thenar muscles. Reaction times and speed of movement were assessed using button presses in response to auditory tones.

RESULTS: Patients had higher (P<.05) self-assessed indices of fatigue (7/10) than for pain (5/10), anxiety (4/10) or depression (3/10). Mean (+/-S.E.M.) simple reaction times (SRTs) were longer (P<.05) in the patients (275+/-19 ms) than in the controls (219+/-9 ms); choice reaction times (CRTs) were not significantly longer in the patients. Movement times, once a reaction task had been initiated, were longer (P<.05) in the patients in both SRTs (patients, 248+/-13 ms; controls, 174+/-9 ms) and CRTs (patients, 269+/-13 ms; controls, 206+/-12 ms). There was no difference (P>.05) in threshold or latency of MEPs in hand muscles between the patients (threshold, 54.5+/-2.2% maximum stimulator output [% MSO]; latency 22+/-0.3 ms) and controls (threshold 54.6+/-3.6% MSO; latency 22.9+/-0.5 ms). Regression analysis showed no correlation (P>.05) of SRTs with either threshold for MEPs or fatigue index.

CONCLUSION: Corticospinal conduction times and excitability were within the normal range despite a slower performance time for motor tasks and an increased feeling of fatigue. This suggests that the feeling of fatigue and the slowness of movement seen in CFS are manifest outside the corticospinal system.

 

Source: Davey NJ, Puri BK, Nowicky AV, Main J, Zaman R. Voluntary motor function in patients with chronic fatigue syndrome. J Psychosom Res. 2001 Jan;50(1):17-20. http://www.ncbi.nlm.nih.gov/pubmed/11259796

 

Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome

Abstract:

OBJECTIVE: We have investigated the possibility of a central basis for the complaints of fatigue and poor exercise tolerance in subjects with chronic fatigue syndrome (CFS).

METHODS: Transcranial magnetic stimulation of the motor cortex was used to measure sequential changes in motor evoked potential (MEP) amplitude, post-excitatory silent period (SP) duration and twitch force of the biceps brachii muscle during a 20% maximum isometric elbow flexor contraction maintained to the point of exhaustion. Ten patients with post-infectious CFS and 10 age- and sex-matched control subjects were studied. Results were analysed using non-parametric repeated measures analysis of variance (Friedman’s test) and Mann-Whitney U-tests for intra- and inter-group comparisons respectively.

RESULTS: Mean endurance time for the CFS group was lower (13.1+/-3.2 min, mean +/- SEM) than controls (18.6+/-2.6 min, P < 0.05) and CFS subjects reported higher ratings of perceived exertion. During the exercise period MEP amplitude and SP duration increased in both groups but to a lesser extent in CFS subjects. Interpolated twitch force amplitude also increased during exercise, being more pronounced in CFS subjects.

CONCLUSION: The findings are in keeping with an exercise-related diminution in central motor drive in association with an increased perception of effort in CFS.

 

Source: Sacco P, Hope PA, Thickbroom GW, Byrnes ML, Mastaglia FL. Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome. Clin Neurophysiol. 1999 Nov;110(11):1883-91. http://www.ncbi.nlm.nih.gov/pubmed/10576483

 

Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression

Abstract:

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects, 12 patients with chronic fatigue syndrome, and 10 depressed patients. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until they were unable to maintain half maximal force.

MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean pre-exercise MEP amplitude in normal subjects, 126% in chronic fatigue patients, and 155% in depressed patients, indicating postexercise MEP facilitation in all three groups. The increases in the patient groups, however, were significantly lower than normal.

The mean amplitudes of MEPs recorded within the first few minutes after the last exercise sets in all three groups were approximately half their mean pre-exercise MEP amplitudes. This postexercise MEP depression was similar in all groups. We conclude that postexercise cortical excitability is significantly reduced in patients with chronic fatigue syndrome and in depressed patients compared with that of normal subjects.

 

Source: Samii A, Wassermann EM, Ikoma K, Mercuri B, George MS, O’Fallon A, Dale JK, Straus SE, Hallett M. Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression. Neurology. 1996 Dec;47(6):1410-4. http://www.ncbi.nlm.nih.gov/pubmed/8960719

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214