Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the proportions of type 1 and type 2 muscle fibres and the degree of muscle fibre atrophy and hypertrophy in patients with chronic fatigue syndrome in relation to lactate responses to exercise, and to determine to what extent any abnormalities found might be due to inactivity.

METHODS: Quadriceps needle muscle biopsies were obtained from 105 patients with chronic fatigue syndrome and the proportions of type 1 and 2 fibres and fibre atrophy and hypertrophy factors were determined from histochemical preparations, using a semiautomated image analysis system. Forty one randomly selected biopsies were also examined by electron microscopy. Lactate responses to exercise were measured in the subanaerobic threshold exercise test (SATET).

RESULTS: Inactivity would be expected to result in a shift to type 2 fibre predominance and fibre atrophy, but type 1 predominance (23%) was more common than type 2 predominance (3%), and fibre atrophy was found in only 10.4% of cases. Patients with increased lactate responses to exercise did have significantly fewer type 1 muscle fibres (p<0.043 males, p<0.0003 females), but there was no evidence that this group was less active than the patients with normal lactate responses. No significant ultrastructural abnormalities were found.

CONCLUSION: Muscle histometry in patients with chronic fatigue syndrome generally did not show the changes expected as a result of inactivity. However, patients with abnormal lactate responses to exercise had a significantly lower proportion of mitochondria rich type 1 muscle fibres.

 

Source: Lane RJ, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC. Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):362-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169994/ (Full article)

 

Physical activity in chronic fatigue syndrome: assessment and its role in fatigue

Abstract:

This paper describes the assessment of physical activity in chronic fatigue syndrome (CFS) and investigated the following questions: Do patients with CFS have low levels of physical activity; is there a relationship between actual level of physical activity and fatigue; can self-report measures adequately assess actual level of physical activity; what is the role of cognitions with respect to physical activity; and are results with respect to physical activity specific to CFS?

Three different types of activity measures were used: self-report questionnaires, a 12-day self-observation list, and a motion-sensing device (Actometer) which was used as a reference for actual activity level. Fifty-one patients with CFS, 50 fatigued patients with multiple sclerosis (MS), and 53 healthy subjects participated in this study.

Although none of the self-report questionnaires showed high correlations with the Actometer, questionnaires that require simple ratings of specified activities were related to the Actometer and can be used as acceptable substitutes, in contrast to instruments that require general subjective interpretations of activity that had low or non-significant correlations with the Actometer.

Actometer results showed that CFS patients and MS patients had similar activity levels and both groups were significantly less active than healthy subjects. Compared to MS patients, CFS patients were more likely to indicate that they had been less active than other persons they knew. Activities which patients expected to result in higher fatigue levels were less frequently performed. Patients with CFS had significantly higher scores on this measure than MS patients and healthy subjects. Low levels of physical activity were related to severe fatigue in CFS but not in MS.

In conclusion, although CFS patients have similar low activity levels than MS patients, there are also important differences between both groups: in CFS cognitive factors are more prominently involved in producing the low activity levels than in MS and in CFS patients activity level is related to fatigue but not in MS.

 

Source: Vercoulen JH, Bazelmans E, Swanink CM, Fennis JF, Galama JM, Jongen PJ, Hommes O, Van der Meer JW, Bleijenberg G. Physical activity in chronic fatigue syndrome: assessment and its role in fatigue. J Psychiatr Res. 1997 Nov-Dec;31(6):661-73. http://www.ncbi.nlm.nih.gov/pubmed/9447571

 

Graded exercise in chronic fatigue syndrome. Chronic fatigue syndrome is heterogeneous condition

Comment on: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Editor—The study reported by Kathy Y Fulcher and Peter D White will provide new hope to many patients diagnosed as having the chronic fatigue syndrome.1 Before exercise regimens become the treatment of choice, however, it is worth noting that over two fifths of the patients in the study reported no or little improvement. It is a pity that the researchers did not compare those who were “very much better” with those who were not, in terms of variables such as the onset of illness (acute or gradual, history of infection) 2 and the presence of additional symptoms frequently associated with the syndrome—for example, cognitive difficulties, nausea, and malaise after exercise. This might have shown whether one particular subgroup fared better than another, allowing doctors to tailor their advice and further improve patients’ care.3

The possibility that subgroups may have different prognoses also deserves consideration. For instance, a recent study found that 70% of patients diagnosed as having epidemic neuromyasthenia recovered within two years.4 If two thirds of the subjects studied by Fulcher and White also had disease of acute onset linked to infection, one could argue that the exercise regimen reflected the natural course of the illness while the flexibility training made patients worse.

A final point concerns the 20 subjects taking full dose antidepressants. The authors do not specify why these drugs were being taken by people who did not have clinical depression or sleep disorders. Moreover, since many patients with the chronic fatigue syndrome cannot tolerate therapeutic doses of antidepressants,5 some of the reported fatigue and malaise may have been drug induced.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127599/pdf/9361552.pdf

 

Source: Goudsmit EM. Graded exercise in chronic fatigue syndrome. Chronic fatigue syndrome is heterogeneous condition. BMJ. 1997 Oct 11;315(7113):948. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127599/

 

Graded exercise in chronic fatigue syndrome. Patients were selected group

Comment on: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Editor—Kathy Y Fulcher and Peter D White conclude that their findings support the use of graded aerobic exercise in the management of the chronic fatigue syndrome.1 Those readers who delve no further than the abstract and key points may welcome this “take home message.”

Several flaws in the paper, however, make accurate interpretation of the findings difficult and greatly limit its applicability. Firstly, less than two fifths of those screened for the trial actually entered it. Many of those who did not enter it were excluded on the basis of current psychiatric disorder, even though the Oxford criteria used by the authors do not specifically exclude patients with anxiety and depression.2 Given that this is already a subgroup selected by their referral to psychiatric outpatient departments, to select out those with a current psychiatric disorder makes them an unusual group indeed.

Secondly, successful randomisation should make the intervention and control groups similar. Such comparability should enable the problem of confounders, known or unknown, to be accounted for. Evidence of the comparability of cases and controls should be presented.3 Age and sex are almost universal confounders. In this study one might also add body mass index, duration of illness, and even previous athletic training as other possible confounders. The paper does not break down the age and sex of the two groups to enable comparison.

Thirdly, the main outcome measure is the self rated clinical global impression change score. This score is a validated measure of overall change.4 However, the validity of the subsequent categorisation of patients into those with a score of 1 or 2 and those with a score of 3-7, and whether this was a post hoc categorisation, is not stated. A categorisation into 1-3 (all scores representing an improvement) and 4-7 (the rest) would not have produced a significant change. Numerous other physiological outcome measures are provided, but more clinically relevant would have been consultation rates, use of drug treatment, and time off work (time off work was measured only at one year, after the crossover). In short, for those considering the options for managing this condition, especially those who commission services, the message should be that we need more information before we can tell if graded exercise will help most patients with the chronic fatigue syndrome.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127633/pdf/9361551.pdf

 

Source: Sadler M. Graded exercise in chronic fatigue syndrome. Patients were selected group. BMJ. 1997 Oct 11;315(7113):947-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127633/

 

Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results

Comment on:

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

Managing chronic fatigue syndrome in children. [BMJ. 1997]

 

Editor—“Editor’s choice” in the issue of 7 June states, “we agree that myalgic encephalomyelitis (or chronic fatigue syndrome) is a serious condition” and “all conditions have a mental and physical component.” This is the stance of the patient organisations supporting patients with this condition. Unfortunately, some doctors have trivialised this illness; ridiculed patients and their supporters; and subjected a few of them, including children, to oppressive, perhaps even abusive, forms of treatment. Hopefully, this is now a thing of the past. We need, as Harvey Marcovitch says, to explore what might be done to help them.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127632/pdf/9361550.pdf

 

Source: Franklin AJ. Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results. BMJ. 1997 Oct 11;315(7113):947; author reply 948. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127632/

 

Graded exercise in chronic fatigue syndrome. Patients should have initial period of rest before gradual increase in activity

Erratum in: BMJ 1997 Nov 1;315(7116):1165.

Comment on: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Editor—We remain firmly opposed to exercise programmes that encourage patients with the chronic fatigue syndrome to increase their levels of physical activity progressively without making allowance for fluctuating levels of disablement. Nevertheless, we welcome Kathy Y Fulcher and Peter D White’s finding that an individually tailored programme can produce benefits in a carefully selected subset.1 We have concerns, however, about the way in which these results have been oversimplified in the media and may now be put into practice by health professionals with no experience of this approach to management.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127628/pdf/9361549.pdf

 

Source: Shepherd C, Macintyre A. Graded exercise in chronic fatigue syndrome. Patients should have initial period of rest before gradual increase in activity. BMJ. 1997 Oct 11;315(7113):947; author reply 948. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127628/

 

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome

Abstract:

OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome.

DESIGN: Randomised controlled trial with control treatment crossover after the first follow up examination.

SETTING: Chronic fatigue clinic in a general hospital department of psychiatry.

SUBJECTS: 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance.

INTERVENTIONS: Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy. Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards.

MAIN OUTCOME MEASURE: The self rated clinical global impression change score, “very much better” or “much better” being considered as clinically important.

RESULTS: Four patients receiving exercise and three receiving flexibility treatment dropped out before completion. 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment. Analysis by intention to treat gave similar results (17/33 v 9/33 patients better). Fatigue, functional capacity, and fitness were significantly better after exercise than after flexibility treatment. 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment.

CONCLUSION: These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome.

Comment in:

Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results. [BMJ. 1997]

Managing chronic fatigue syndrome in children. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Chronic fatigue syndrome is heterogeneous condition. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Patients should have initial period of rest before gradual increase in activity. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Patients were selected group. [BMJ. 1997]

 

Source: Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ. 1997 Jun 7;314(7095):1647-52. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126868/ (Full article)

 

Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology

Abstract:

Physical fatigability and avoidance of physically demanding tasks in chronic fatigue syndrome (CFS) were assessed by the achievement or nonachievement of 85% of age-predicted maximal heart rate (target heart rate, THR) during incremental exercise. The association with functional status impairment, somatization, and psychopathology was examined.

A statistically significant association was demonstrated between this physical fatigability variable and impairment, and a trend was found for an association with somatization. No association was demonstrated with psychopathology. These results are in accordance with the cognitive-behavioral model of CFS, suggesting a major contribution of avoidance behavior to functional status impairment; however, neither anxiety nor depression seem to be involved in the avoidance behavior.

Aerobic work capacity was compared between CFS and healthy controls achieving THR. Physical deconditioning with early involvement of anaerobic metabolism was demonstrated in this CFS subgroup.

Half of the CFS patients who did not achieve THR did not reach the anaerobic threshold. This finding argues against an association in CFS between avoidance of physically demanding tasks and early anaerobic metabolism during effort.

 

Source: Fischler B, Dendale P, Michiels V, Cluydts R, Kaufman L, De Meirleir K. Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology. J Psychosom Res. 1997 Apr;42(4):369-78. http://www.ncbi.nlm.nih.gov/pubmed/9160276

 

Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if patients with the chronic fatigue syndrome have less vagal power during walking and rest periods following walking, in comparison to a group of healthy controls.

Eleven patients (ten women and one man) who fulfilled the case definition for chronic fatigue syndrome modified to reduce heterogeneity and eleven healthy, but sedentary, age- and sex-matched controls walked on a treadmill at 2.5 mph four times each for 4 min duration. Between each period of walking, subjects were given a 4-min seated rest period. Vagal power, a Fourier-based measure of cardiac, parasympathetic activity in the frequency range of 0.15 to 1.0 Hz, was computed.

In each period of walking and in one period of rest, patients had significantly less vagal power than the control subjects despite there being no significant group-wise differences in mean heart rate, tidal volume, minute volume, respiratory rate, oxygen consumption or total spectrum power. Further, patients had a significant decline in resting vagal power after periods of walking.

These results suggest a subtle abnormality in vagal activity to the heart in patients with the chronic fatigue syndrome and may explain, in part, their post-exertional symptom exacerbation.

 

Source: Cordero DL, Sisto SA, Tapp WN, LaManca JJ, Pareja JG, Natelson BH. Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome. Clin Auton Res. 1996 Dec;6(6):329-33. http://www.ncbi.nlm.nih.gov/pubmed/8985621

 

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