Tag: Natelson

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory

Abstract:

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT).

We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for.

Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99).

Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

 

Source: Lange G, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu WC, Deluca J, Natelson BH. Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory. Neuroimage. 2005 Jun;26(2):513-24. Epub 2005 Apr 7. http://www.ncbi.nlm.nih.gov/pubmed/15907308

 

Spinal fluid abnormalities in patients with chronic fatigue syndrome

Abstract:

Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls.

Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having comorbid depression than those with normal fluid.

In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls.

The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.

 

Source: Natelson BH, Weaver SA, Tseng CL, Ottenweller JE. Spinal fluid abnormalities in patients with chronic fatigue syndrome. Clin Diagn Lab Immunol. 2005 Jan;12(1):52-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC540195/ (Full article)

 

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome

Abstract:

Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs.

To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT.

While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

 

Source: Yoshiuchi K, Quigley KS, Ohashi K, Yamamoto Y, Natelson BH. Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome. Auton Neurosci. 2004 Jun 30;113(1-2):55-62. http://www.ncbi.nlm.nih.gov/pubmed/15296795

 

Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans

Abstract:

Genes associated with muscle metabolism and physical endurance were evaluated for variants that may contribute to the etiology of medically unexplained severe and chronic fatigue. Subjects included 49 Gulf War veterans and 61 nonveterans with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) and 30 veterans and 45 nonveterans who served as healthy controls. Increased risk for CFS/ICF was associated with alterations of the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene within the Gulf War veteran sample only. The I allele frequency was decreased in affected versus unaffected veterans (0.15 versus 0.48; odds ratio [OR], 5.08; 95% confidence interval [CI], 1.97-13.35; P < 0.0001). Correspondingly, the II genotype was decreased fourfold in affected veterans (0.08 versus 0.35; OR = 5.87; 95% CI: 1.21-28.36; P = 0.02), and the DD genotype was increased twofold (0.78 versus 0.39; OR, 5.4; 95% CI, 1.6-18.4; P = 0.007). Veterans with the DD genotype were eight times more likely to develop CFS/ICF than were those with the II genotype (OR, 8.30; 95% CI, 1.50-56.09; P = 0.009).

 

Source: Vladutiu GD, Natelson BH. Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans. Muscle Nerve. 2004 Jul;30(1):38-43. http://www.ncbi.nlm.nih.gov/pubmed/15221876

 

Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome

Abstract:

OBJECTIVES: Our objectives were to study the temporal correlation of physical activity time series in patients with chronic fatigue syndrome (CFS) during normal daily life and to examine if it could identify the altered physical activity in these patients.

METHODS: Fractal scaling exponents of diurnal and nocturnal physical activity time series in 10 CFS patients and 6 healthy control subjects (CON) were calculated by the detrended fluctuation analysis (DFA) and the wavelet transform modulus maxima (WTMM) method. We hypothesized that, due to their illness- and/or fatigue-induced resting episodes, altered physical activity patterns in CFS patients might be observed at the interruption of activity bursts. Thus, we further developed a new method, the wavelet transform negative modulus maxima (WTNMM) method, which could evaluate the temporal correlation at the interruption of activities. We compared the fractal scaling exponents for CFS and CON by each method.

RESULTS: Both for CFS and CON, we found the fractal time structures in their diurnal physical activity records for at least up to 35 minutes. No group difference was found in nocturnal activities. The WTNMM method revealed that, in diurnal activities, CFS patients had significantly (p < 0.01) smaller fractal scaling exponent (0.87 +/- 0.03) compared to controls (1.01 +/- 0.03). Such a difference was identified neither by the DFA nor WTMM method.

CONCLUSIONS: CFS patients had more abrupt interruptions of voluntary physical activity during diurnal periods in normal daily life, probed by the decreased correlation in the negative modulus maxima of the wavelet-transformed activity data, possibly due to their exaggerated fatigue.

 

Source: Ohashi K, Bleijenberg G, van der Werf S, Prins J, Amaral LA, Natelson BH, Yamamoto Y. Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome. Methods Inf Med. 2004;43(1):26-9. http://www.ncbi.nlm.nih.gov/pubmed/15026831

 

Neuropsychological deficits in patients with chronic fatigue syndrome

Abstract:

The degree of neuropsychological dysfunction across multiple domains was examined in individuals suffering from chronic fatigue syndrome(CFS). In this descriptive study, a similar series of neuropsychological tests was administered to a group of CFS patients and healthy participants. More specifically, CFS patients (n = 141) who met the 1994 Case Definition criteria were compared to 76 healthy control participants on tests of memory, attention (concentration), speed of information processing, motor speed, and executive functioning.

On the 18 measures administered, CFS patients scored 1 standard deviation below the healthy mean on nine measures and scored 2 standard deviations below the healthy mean on four of the measures. Moreover, results indicated that CFS patients were more likely than healthy controls to fail (1.6 SD below the healthy mean) at least one test in each of the following domains: attention, speed of information processing, and motor speed, but not on measures of memory and executive functioning. Finally, CFS patients demonstrated a greater total number of tests failed across domains.

 

Source: Busichio K, Tiersky LA, Deluca J, Natelson BH. Neuropsychological deficits in patients with chronic fatigue syndrome. J Int Neuropsychol Soc. 2004 Mar;10(2):278-85. http://www.ncbi.nlm.nih.gov/pubmed/15012848

 

Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness

Abstract:

Abnormal cardiovascular stress responses have been reported in Gulf War veterans with chronic fatigue. However, many of these veterans also suffer from posttraumatic stress disorder (PTSD), which could potentially explain the reported abnormalities. To test this hypothesis, 55 Gulf veterans (GVs) with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) were stratified into groups with (N=16) and without (N=39) comorbid PTSD, and were compared to healthy Gulf veterans (N=47) on cardiovascular responses to a series of stressors.

The CFS/ICF with PTSD group had lower blood pressure responses to speech and arithmetic tasks, and more precipitous declines and slower recoveries in blood pressure after standing up than the controls. Similar trends in the CF/ICF group without PTSD were not significant, however. Both CFS/ICF groups had blunted increases in peripheral vascular resistance during mental tasks. However, only the veterans with comorbid PTSD had diminished cardiac output responses to the mental stressors and excessive vasodilatory responses to standing. Symptoms of posttraumatic stress were significant predictors of hypotensive postural responses, but only in veterans reporting a significant exposure to wartime stress.

We conclude that comorbid PTSD contributes to dysregulation of cardiovascular responses to mental and postural stressors in Gulf veterans with medically unexplained fatiguing illness, and may provide a physiological basis for increased somatic complaints in Gulf veterans with symptoms of posttraumatic stress.

 

Source: Peckerman A, Dahl K, Chemitiganti R, LaManca JJ, Ottenweller JE, Natelson BH. Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness. Auton Neurosci. 2003 Oct 31;108(1-2):63-72. http://www.ncbi.nlm.nih.gov/pubmed/14614966

 

Muscle metabolism with blood flow restriction in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) is associated with reduced blood flow and muscle oxidative metabolism. Patients with CFS according to Centers for Disease Control criteria (n = 19) were compared with normal sedentary subjects (n = 11).

Muscle blood flow was measured in the femoral artery with Doppler ultrasound after exercise. Muscle metabolism was measured in the medial gastrocnemius muscle with (31)P-magnetic resonance spectroscopy. Muscle oxygen saturation and blood volume were measured using near-infrared spectroscopy. CFS and controls were not different in hyperemic blood flow or phosphocreatine recovery rate. Cuff pressures of 50, 60, 70, 80, and 90 mmHg were used to partially restrict blood flow during recovery. All pressures reduced blood flow and oxidative metabolism, with 90 mmHg reducing blood flow by 46% and oxidative metabolism by 30.7% in CFS patients.

Hyperemic blood flow during partial cuff occlusion was significantly reduced in CFS patients (P < 0.01), and recovery of oxygen saturation was slower (P < 0.05). No differences were seen in the amount of reduction in metabolism with partially reduced blood flow.

In conclusion, CFS patients showed evidence of reduced hyperemic flow and reduced oxygen delivery but no evidence that this impaired muscle metabolism. Thus CFS patients might have altered control of blood flow, but this is unlikely to influence muscle metabolism. Furthermore, abnormalities in muscle metabolism do not appear to be responsible for the CFS symptoms.

 

Source: McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH. Muscle metabolism with blood flow restriction in chronic fatigue syndrome. J Appl Physiol (1985). 2004 Mar;96(3):871-8. Epub 2003 Oct 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680353/ (Full article)

 

Aerobic capacity of Gulf War veterans with chronic fatigue syndrome

Abstract:

A large overlap exists between the diagnosis of chronic fatigue syndrome (CFS) and the unexplained symptoms reported by many Gulf War veterans (GV). Previous investigations have reported reduced aerobic capacity in civilians with CFS. The present investigation examined metabolic responses to maximal exercise in GVs with CFS compared with healthy GVs.

Cardiorespiratory and metabolic responses were recorded during a maximal exercise test on a cycle ergometer. The groups were not different in any demographic category (p > 0.05) or self-reported physical activity (p > 0.05). No differences were observed between groups for maximal oxygen uptake (28.9 +/- 6.7 mL/kg/min for CFS vs. 30.8 +/- 7.1 mL/kg/min for controls; p = 0.39), heart rate (155.8 +/- 16.1 bpm for CFS vs. 163.3 +/- 14.9 bpm for controls; p = 0.17), exercise time (9.6 +/- 1.5 minutes for CFS vs. 10.2 +/- 1.4 minutes for controls; p = 0.26), or workload achieved (208 +/- 36.7 W for CFS vs. 224 +/- 42.9 W for controls; p = 0.25). Likewise, no differences were observed at submaximal intensities (p > 0.05).

Compared with healthy controls, GVs who report multiple medically unexplained symptoms and meet criteria for CFS do not show a decreased exercise capacity. Thus, it does not appear that the pathology of the GVs with CFS includes a deficiency with mobilizing the cardiopulmonary system for strenuous physical effort.

 

Source: Nagelkirk PR, Cook DB, Peckerman A, Kesil W, Sakowski T, Natelson BH, LaManca JJ. Aerobic capacity of Gulf War veterans with chronic fatigue syndrome. Mil Med. 2003 Sep;168(9):750-5. http://www.ncbi.nlm.nih.gov/pubmed/14529252

 

Baroreceptor reflex and integrative stress responses in chronic fatigue syndrome

Abstract:

OBJECTIVE: Altered cardiovascular responses to mental and postural stressors have been reported in chronic fatigue syndrome (CFS). This study examined whether those findings may involve changes in baroreceptor reflex functioning.

METHODS: Chronotropic baroreceptor reflex (by sequential analysis) and cardiovascular stress responses were recorded during postural (5-minute of active standing) and cognitive (speech task) stress testing in patients with CFS grouped into cases with severe (N = 21) or less severe (N = 22) illness, and in 29 matched control subjects.

RESULTS: Patients with CFS had a greater decline in baroreceptor reflex sensitivity (BRS) during standing, although only those with severe CFS were significantly different from the controls. Systolic blood pressure declined during standing in the control group but was maintained in the CFS patients. In contrast, the patients with less severe CFS had blunted increases in blood pressure during the speech task, which could not, however, be explained by inadequate inhibition of the baroreceptor reflex, with all groups showing an appropriate reduction in BRS during the task.

CONCLUSIONS: These results indicate that in CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex. This study also suggests that classifying patients with CFS on illness severity may discriminate between patients with abnormalities in peripheral vs. central mechanisms of cardiovascular stress responses.

 

Source: Peckerman A, LaManca JJ, Qureishi B, Dahl KA, Golfetti R, Yamamoto Y, Natelson BH. Baroreceptor reflex and integrative stress responses in chronic fatigue syndrome. Psychosom Med. 2003 Sep-Oct;65(5):889-95. http://www.ncbi.nlm.nih.gov/pubmed/14508037