Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors

Abstract:

The literature is reviewed and data are presented that relate to a model we have developed to account for the perpetuation of the perplexing disorder currently termed chronic fatigue syndrome (CFS). In patients with CFS there is chronic lymphocyte overactivation with cytokine abnormalities that include perturbations in plasma levels of proinflammatory cytokines and decrease in the ratio of Type 1 to Type 2 cytokines produced by lymphocytes in vitro following mitogen stimulation. The initiation of the syndrome is frequently sudden and often follows an acute viral illness.

Our model for the subsequent chronicity of this disorder holds that the interaction of psychological factors (distress associated with either CFS-related symptoms or other stressful life events) and the immunologic dysfunction contribute to (a) CFS-related physical symptoms (e.g., perception of fatigue and cognitive difficulties, fever, muscle and joint pain) and increases in illness burden and (b) impaired immune surveillance associated with cytotoxic lymphocytes with resulting activation of latent herpes viruses.

 

Source: Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG. Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors. Appl Neuropsychol. 2001;8(1):51-64. http://www.ncbi.nlm.nih.gov/pubmed/11388124

 

Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome

Abstract:

The longitudinal course of subjective and objective neuropsychological functioning, psychological functioning, disability level, and employment status in chronic fatigue syndrome (CFS) was examined. The relations among several key outcomes at follow-up, as well as the baseline characteristics that predict change (e.g., improvement), were also evaluated.

The study sample consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Centers for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM = 1.7) months following their initial visit (range = 24-63 months).

Results indicated that objective and subjective attention abilities, mood, level of fatigue, and disability improve over time in individuals with CFS. Moreover, improvements in these areas were found to be interrelated at follow-up. Finally, psychiatric status, age, and between-test duration were significant predictors of outcome. Overall, the prognosis for CFS appears to be poor, as the majority of participants remained functionally impaired over time and were unemployed at follow-up, despite the noted improvements.

 

Source: Tiersky LA, DeLuca J, Hill N, Dhar SK, Johnson SK, Lange G, Rappolt G, Natelson BH. Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):41-50. http://www.ncbi.nlm.nih.gov/pubmed/11388123

 

Divided attention deficits in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients and controls were compared on a variety of mood state, personality, and neuropsychological measures, including memory, word finding, and attentional tasks that required participants to focus, sustain, or divide their attention, or to perform a combination of these functions.

CFS patients demonstrated a selective deficit on 3 measures of divided attention. Their performance on the other neuropsychological tests of intelligence, fluency, and memory was no different than that of normal controls despite their reports of generally diminished cognitive capacity. There was an inverse relation between CFS patient fatigue severity and performance on 1 of the divided attention measures.

Given these findings, it is probable that CFS patients will report more cognitive difficulties in real-life situations that cause them to divide their effort or rapidly reallocate cognitive resources between 2 response channels (vision and audition).

 

Source: Ross S, Fantie B, Straus SF, Grafman J. Divided attention deficits in patients with chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):4-11. http://www.ncbi.nlm.nih.gov/pubmed/11388122

 

Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact?

Abstract:

This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function.

Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise.

The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.

 

Source: Claypoole K, Mahurin R, Fischer ME, Goldberg J, Schmaling KB, Schoene RB, Ashton S, Buchwald D. Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact? Appl Neuropsychol. 2001;8(1):31-40. http://www.ncbi.nlm.nih.gov/pubmed/11388121

 

Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome

Abstract:

Previous qualitative volumetric assessment of lateral ventricular enlargement in chronic fatigue syndrome (CFS) has provided evidence for subtle structural changes in the brains of some individuals with CFS. The aim of this pilot study was to determine whether a more sensitive quantitative assessment of the lateral ventricular system would support the previous qualitative findings.

In this study, we compared the total lateral ventricular volume, as well as the right and left hemisphere subcomponents in 28 participants with CFS and 15 controls. Ventricular volumes in the CFS group were larger than in control groups, a difference that approached statistical significance. Group differences in ventricular asymmetry were not observed. The results of this study provide further evidence of subtle pathophysiological changes in the brains of participants with CFS.

 

Source: Lange G, Holodny AI, DeLuca J, Lee HJ, Yan XH, Steffener J, Natelson BH. Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):23-30. http://www.ncbi.nlm.nih.gov/pubmed/11388120

 

Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression

Abstract:

Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability.

A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls.

After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.

 

Source: Daly E, Komaroff AL, Bloomingdale K, Wilson S, Albert MS. Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol. 2001;8(1):12-22. http://www.ncbi.nlm.nih.gov/pubmed/11388119

 

How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome?

Abstract:

In order to study both the prevalence of Primary Sleep Disorders (PSD) and sleepiness, and their association to the Chronic Fatigue Syndrome (CFS), 46 unselected outpatients (34 women, mean age 36.5) were examined clinically and underwent two nights of all-night polysomnography and multiple sleep latency tests (MSLT).

Forty-six percent presented with a Sleep Apnea/Hypopnea Syndrome Index (AHI>=5), 5% with a Periodic Limb Movements syndrome. No subject received a diagnosis of Narcolepsy or Idiopathic Hypersomnia. Thirty percent showed the presence of objective sleepiness as measured by MSLT<10 minutes. Objective and subjective measures of sleepiness were not associated with CFS, nor with the double diagnosis of CFS and a PSD. The presence of PSD or sleepiness was not associated with any of the clinical scales that were used to measure anxiety, depression, somatisation, physical or mental fatigue, or functional status impairment.

Fifty-four percent of CFS patients had no PSD, and 69% no sleepiness. These patients could not be distinguished clinically from patients having a PSD or from those with sleepiness. Therefore, it is unlikely that CFS is simply a somatic expression of any PSD observed in our sample or of sleepiness per se.

 

Source: Le Bon O, Fischler B, Hoffmann G, Murphy JR, De Meirleir K, Cluydts R, Pelc I. How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome? Sleep Res Online. 2000;3(2):43-8. http://www.ncbi.nlm.nih.gov/pubmed/11382899

 

A community-based study of seasonal variation in the onset of chronic fatigue syndrome and idiopathic chronic fatigue

Abstract:

One proposed hypothesis regarding the etiology of chronic fatigue syndrome (CFS) is that there is a subgroup of patients in which symptom onset is precipitated by a viral infection. If this is indeed true, then one would anticipate a greater incidence of the emergence of CFS symptoms during months when viral infections occur with the greatest frequency. The current community-based epidemiology study examined the month of symptom onset for 31 patients with CFS and 44 others with idiopathic chronic fatigue (ICF). It was determined that the distribution of the month of illness onset for the CFS and ICF groups was nonrandom, with greater numbers of participants than expected reporting an onset of CFS and ICF during January.

 

Source: Jason LA, Taylor RR, Carrico AW. A community-based study of seasonal variation in the onset of chronic fatigue syndrome and idiopathic chronic fatigue. Chronobiol Int. 2001 Mar;18(2):315-9. http://www.ncbi.nlm.nih.gov/pubmed/11379670

 

The effect of exercise on gait and balance in patients with chronic fatigue syndrome

Abstract:

This study investigated anecdotal reports of gait and balance abnormalities in subjects with Chronic Fatigue Syndrome (CFS) by examining the effects of a light exercise test on postural sway and various gait parameters. Tests were performed on 11 CFS patients and 11 age- and sex-matched sedentary controls. Results demonstrated that postural sway was not significantly different in both groups before or after the exercise test. There were, however, significant differences in gait parameters between the two groups confirming anecdotal evidence, but these differences were not exacerbated by the exercise test. Heart rate responses demonstrated that both groups were exercising at similar loads, although this was perceived to be higher by the CFS group.

 

Source: Paul LM, Wood L, Maclaren W. Gait Posture. 2001 Jul;14(1):19-27. The effect of exercise on gait and balance in patients with chronic fatigue syndrome. Gait Posture. 2001 Jul;14(1):19-27. http://www.ncbi.nlm.nih.gov/pubmed/11378421

 

Monozygotic twins discordant for chronic fatigue syndrome: regional cerebral blood flow SPECT

Abstract:

PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS.

MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m-hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors.

RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging.

CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.

 

Source: Lewis DH, Mayberg HS, Fischer ME, Goldberg J, Ashton S, Graham MM, Buchwald D. Monozygotic twins discordant for chronic fatigue syndrome: regional cerebral blood flow SPECT. Radiology. 2001 Jun;219(3):766-73. http://www.ncbi.nlm.nih.gov/pubmed/11376266