Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome

Abstract:

PURPOSE: To evaluate the aerobic power (as maximum volume of oxygen consumed [VO2 max]) of women with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Twenty-one women with CFS and 22 sedentary healthy controls (CON) were studied at the CFS Cooperative Research Center Exercise Laboratory at the VA Medical Center, East Orange, New Jersey. Performance was measured on an incremental treadmill protocol walking to exhaustion. Expired gases were analyzed by a metabolic system, heart rate was recorded continuously, and ratings of perceived exertion (RPE) were taken at each workload. The groups were divided into those who achieved VO2 max (CFS-MAX and CON-MAX) and those who stopped at a submaximal level (CFS-NOMAX and CON-NOMAX) by using standard criteria.

RESULTS: Seventeen CON and 10 CFS subjects achieved VO2 max. The VO2 max (mL/kg/min) of the CFS-MAX (28.1 +/- 5.1) was lower than that of the CON-MAX (32.1 +/- 4.3, P = 0.05). The CFS-MAX achieved 98 +/- 11% of predicted VO2 max. The CFS group had a higher RPE at the same absolute workloads as controls (P < 0.01) but not the same relative workloads.

CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness.

Comment in:

Exercise limits in chronic fatigue syndrome. [Am J Med. 1997]

Graded exercise testing and chronic fatigue syndrome. [Am J Med. 1997]

 

Source: Sisto SA, LaManca J, Cordero DL, Bergen MT, Ellis SP, Drastal S, Boda WL, Tapp WN, Natelson BH. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. 1996 Jun;100(6):634-40. http://www.ncbi.nlm.nih.gov/pubmed/8678084

 

Reduced oxidative muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15).

CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 +/- 2.8 mmol/L/min, mean +/- SE) compared to controls (53.8 +/- 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14).

In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.

Comment in: Chronic fatigue syndrome and skeletal muscle mitochondrial function. [Muscle Nerve. 1997]

 

Source: McCully KK, Natelson BH, Iotti S, Sisto S, Leigh JS Jr. Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve. 1996 May;19(5):621-5. http://www.ncbi.nlm.nih.gov/pubmed/8618560

 

Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome

Abstract:

Because of the striking similarity of the clinical manifestations produced by use of the drug reserpine and seen in patients with the chronic fatigue syndrome (CFS), we theorized that CFS was a disorder of reduced central sympathetic drive. Because of the pharmacology of control of this central sympathetic system, we further postulated that CFS symptoms would respond quickly to low dose treatment with a monamine oxidase inhibitor. To test these hypotheses, we designed a randomized, double blind placebo controlled study using phenelzine.

No patient in the trial had a diagnosis of lifetime or current psychiatric disorder and none had depressed mood in the range of clinically depressed patients on a paper and pencil test of depression. Patients in the placebo group received placebo for 6 weeks while those in the drug treatment group were treated in three 2-week segments-placebo, 15 mg phenelzine every other day, and then 15 mg daily. This treatment regimen produced a significant pattern of improvement compared to worsening in 20 self report vehicles of CFS symptoms, illness severity, mood or functional status.

Thus the data support our hypothesis of reduced sympathetic drive, although an alternative hypothesis of pain alleviation is also possible. The study design also allowed us to evaluate patients for a placebo effect: no evidence for this was found, suggesting that CFS is not an illness due to patients’ being overly suggestible.

 

Source: Natelson BH, Cheu J, Pareja J, Ellis SP, Policastro T, Findley TW. Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome. Psychopharmacology (Berl). 1996 Apr;124(3):226-30. http://www.ncbi.nlm.nih.gov/pubmed/8740043

 

Use of exercise for treatment of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a condition that results in moderate to severe disability, the primary feature of which is fatigue of unknown origin. There is a lot of interest in classifying, characterising and treating patients with CFS. Currently, the two major theories of a medical cause of CFS are viral infection and immune dysregulation.

Patients report critical reductions in levels of physical activity, and many experience ‘relapses’ of severe symptoms following even moderate levels of exertion. Despite this, most studies report CFS patients to have normal muscle strength and either normal or slightly reduced muscle endurance.

Histological and metabolic studies report mixed results: CFS patients have either no impairment or mild impairment of mitochondria and oxidative metabolism compared with sedentary controls.

Current treatments for CFS are symptom-based, with psychological, pharmacological and rehabilitation treatments providing some relief but no cure. Immunological and nutritional treatments have been tried but have not provided reproducible benefits. Exercise training programmes are thought to be beneficial (if ‘relapses’ can be avoided), although few controlled studies have been performed.

CFS is a long-lasting disorder that can slowly improve with time, but often does not. Further studies are needed to better understand the multiple factors that can cause chronic fatigue illness, as well as the effect that exercise training has on the symptoms of CFS.

 

Source: McCully KK, Sisto SA, Natelson BH. Use of exercise for treatment of chronic fatigue syndrome. Sports Med. 1996 Jan;21(1):35-48. http://www.ncbi.nlm.nih.gov/pubmed/8771284

 

Personality dimensions in the chronic fatigue syndrome: a comparison with multiple sclerosis and depression

Abstract:

This study investigated the relative rates of personality disturbance in chronic fatigue syndrome (CFS). Individuals who met the CDC criteria for CFS were compared to two other fatiguing illness groups, mild multiple sclerosis and depression, as well as sedentary healthy controls.

Subjects were administered a structured psychiatric interview to determine Axis I psychiatric disorders and two self-report instruments to assess Axis II personality disorders and the personality trait of neuroticism.

The depressed group had significantly more personality disorders and elevated neuroticism scores compared with the other three groups. The CFS and MS subjects had intermediary personality scores which were significantly higher than healthy controls.

The CFS group with concurrent depressive disorder (34% of the CFS group) was found to account for most of the personality pathology in the CFS sample. The results are discussed in the context of the relationship between personality variables and fatiguing illness.

 

Source: Johnson SK, DeLuca J, Natelson BH. Personality dimensions in the chronic fatigue syndrome: a comparison with multiple sclerosis and depression. J Psychiatr Res. 1996 Jan-Feb;30(1):9-20. http://www.ncbi.nlm.nih.gov/pubmed/8736462

 

Assessing somatization disorder in the chronic fatigue syndrome

Abstract:

This study was conducted to examine the rates of somatization disorder (SD) in the chronic fatigue syndrome (CFS) relative to other fatiguing illness groups. It further addressed the arbitrary nature of the judgments made in assigning psychiatric vs. physical etiology to symptoms in controversial illnesses such as CFS.

Patients with CFS (N = 42), multiple sclerosis (MS) (N = 18), and depression (N = 21) were compared with healthy individuals (N = 32) on a structured psychiatric interview. The SD section of the Diagnostic Interview Schedule (DIS) III-R was reanalyzed using different criteria sets to diagnose SD. All subjects received a thorough medical history, physical examination, and DIS interview. CFS patients received diagnostic laboratory testing to rule out other causes of fatigue.

This study revealed that changing the attribution of SD symptoms from psychiatric to physical dramatically affected the rates of diagnosing SD in the CFS group. Both the CFS and depressed subjects endorsed a higher percentage of SD symptoms than either the MS or healthy groups, but very few met the strict DSM-III-R criteria for SD. The present study illustrates that the terminology used to interpret the symptoms (ie, psychiatric or physical) will determine which category CFS falls into. The diagnosis of SD is of limited use in populations in which the etiology of the illness has not been established.

 

Source: Johnson SK, DeLuca J, Natelson BH. Assessing somatization disorder in the chronic fatigue syndrome. Psychosom Med. 1996 Jan-Feb;58(1):50-7. http://www.ncbi.nlm.nih.gov/pubmed/8677289

 

A controlled comparison of multiple chemical sensitivities and chronic fatigue syndrome

Abstract:

The present study had two objectives: 1) to determine the characteristics that differentiated subjects with multiple chemical sensitivities (MCS), chemical sensitivities (CS), and chronic fatigue syndrome (CFS); and 2) to evaluate the psychiatric and neuropsychological complaints of these groups relative to normal controls.

A cross-sectional comparison was made of the following groups matched for age, sex, and education: 1) patients whose sensitivities to multiple low level chemical exposures began with a defined exposure (MCS; N = 23); 2) patients with sensitivities to multiple chemicals without a clear date of onset (CS; N = 13); 3) patients meeting CDC criteria for Chronic Fatigue Syndrome (CFS; N = 18); and 4) normal controls (N = 18).

Subjects with sensitivities to chemicals (MCS and CS) reported significantly more lifestyle changes due to chemical sensitivities and significantly more chemical substances that made them ill compared with chronic fatigue and normal controls. MCS, CS, and CFS patients had significantly higher rates of current psychiatric disorders than normal controls and reported significantly more physical symptoms with no medical explanation.

Seventy-four percent of MCS and 61% of CFS did not qualify for any current Axis I psychiatric diagnosis. Chemically sensitive subjects without a defined date of onset (CS) had the highest rate of Axis I psychiatric disorders (69%). On the MMPI-2, 44% of MCS, 42% of CS, 53% of CFS, and none of the controls achieved clinically significant elevations on scales associated with somatoform disorders.

With the exception of one complex test of visual memory, no significant differences were noted among the groups on tests of neuropsychological function. Standardized measures of psychiatric and neuropsychological function did not differentiate subjects with sensitivities to chemicals from those with chronic fatigue. Subjects with sensitivities to chemicals and no clear date of onset had the highest rate of psychiatric morbidity. Standardized neuropsychological tests did not substantiate the cognitive impairment reported symptomatically. Cognitive deficits may become apparent under controlled exposure conditions.

 

Source: Fiedler N, Kipen HM, DeLuca J, Kelly-McNeil K, Natelson B. A controlled comparison of multiple chemical sensitivities and chronic fatigue syndrome. Psychosom Med. 1996 Jan-Feb;58(1):38-49. http://www.ncbi.nlm.nih.gov/pubmed/8677287

 

Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous illness characterized by a high prevalence of psychiatric problems. We reasoned that we could reduce heterogeneity by excluding patients with psychiatric problems preceding CFS.

We compared the functional status, mood, fatigue level, and psychiatric status of this more homogeneous group of CFS patients with the same parameters in patients with mild multiple sclerosis and in patients with major depression or dysthymia.

Patients with CFS and those with multiple sclerosis were similar in terms of level of anger, severity of depression, level of anxiety, and frequency of current psychiatric diagnoses. Patients with CFS resembled depressed patients in having impaired vigor and experiencing substantial fatigue and confusion–problems constituting part of the case definition of CFS.

The group with CFS was not psychologically vulnerable before the development of this condition and maintained adequate networks of social support despite disabling illness.

Stratification to exclude patients with prior psychiatric disease and those with mild CFS allowed us to define a group of patients with CFS who more resembled patients with mild MS than patients with major depression or dysthymia and thus were more likely to have illness with an infectious or immunologic cause. Use of such a stratification strategy should prove important in testing of the viral/immunologic hypothesis of the etiology of CFS.

 

Source: Natelson BH, Johnson SK, DeLuca J, Sisto S, Ellis SP, Hill N, Bergen MT. Reducing heterogeneity in chronic fatigue syndrome: a comparison with depression and multiple sclerosis. Clin Infect Dis. 1995 Nov;21(5):1204-10. http://www.ncbi.nlm.nih.gov/pubmed/8589144

 

Gait abnormalities in chronic fatigue syndrome

Abstract:

To evaluate our clinical impression that patients with the chronic fatigue syndrome (CFS) did not walk normally, we assessed gait kinematics at slow walking speeds (i.e., 0.45, 0.89 and 1.34 m/sec) and 30 m run time speeds on CFS patients and on a comparison group of sedentary controls.

Run time was significantly slower for CFS than control subjects (p < 0.001). There was a significant interaction (p < 0.01) between group and speed for maximum hip angle during stance and swing phase with hip angle being significantly larger at 1.34 m/sec for CFS than controls subjects for both cases (p < 0.05). Knee flexion during stance and swing phases was significantly larger for controls than CFS subjects at 0.45 m/sec (p < 0.01). Ratio of stride length divided by leg length was significantly larger for the control subjects than for the CFS subjects with differences occurring at 0.45 and 0.89 m/sec (p < 0.01) but not 1.34 m/sec.

The data indicate that CFS patients have gait abnormalities when compared to sedentary controls. These could be due to balance problems, muscle weakness, or central nervous system dysfunction; deciding which will require further research. Evaluation of gait may be a useful tool to measure outcome following therapeutic interventions.

 

Source: Boda WL, Natelson BH, Sisto SA, Tapp WN. Gait abnormalities in chronic fatigue syndrome. J Neurol Sci. 1995 Aug;131(2):156-61. http://www.ncbi.nlm.nih.gov/pubmed/7595641

 

Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) often complain of an inability to maintain activity levels and a variety of autonomic-like symptoms that make everyday activity intolerable at times. The purpose of the study was to determine if there were differences in vagal activity at fixed breathing rates in women with CFS.

Twelve women with the diagnosis of CFS between the ages of 32 and 59 years volunteered for the study. Healthy women, who were between the ages of 30 and 49, served as controls. Full signal electrocardiograph and respiratory signals were collected during a paced breathing protocol of three fixed breathing rates (8, 12 and 18 breaths/min) performed in the sitting and standing postures. Vagal activity was analyzed by means of heart rate spectral analysis to determine the subject’s response to specific breathing rates and postures. Heart rate variability was used as a non-invasive method of measuring the parasympathetic component of the autonomic nervous system.

Using this method, although there was significantly less vagal power in the sitting versus the standing postures for both groups, the overall vagal power was significantly lower (p < 0.034) in the CFS group versus healthy controls. Vagal power was also significantly lower (p < 0.01 to p < 0.05) at all breathing rates in both postures except while standing and breathing at 18 breaths/min. Knowledge of the differences in vagal activity for CFS patients may allow stratification for the analysis of other research variables.

 

Source: Sisto SA, Tapp W, Drastal S, Bergen M, DeMasi I, Cordero D, Natelson B. Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome. Clin Auton Res. 1995 Jun;5(3):139-43. http://www.ncbi.nlm.nih.gov/pubmed/7549414