Category: Neurology

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow

Abstract:

Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results. This may be because they used single-photon emission computed tomography to measure brain blood flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses were done after stratifying the CFS patients based on the presence or absence of a current psychiatric disorder.

Flow was diminished in both groups as follows: patients with no current psychiatric disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have reduced absolute cortical blood flow in rather broad areas when compared with data from healthy controls and that those devoid of psychopathology had the most reductions in cortical flow. These data support, in part, our earlier findings that patients devoid of psychopathology are the group most at risk of having some of the symptoms of CFS due to brain dysfunction.

 

Source: Yoshiuchi K, Farkas J, Natelson BH. Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging. 2006 Mar;26(2):83-6. https://www.ncbi.nlm.nih.gov/pubmed/16494597

 

Reliability of physiological, psychological, and cognitive variables in chronic fatigue syndrome

Abstract:

The purpose of this study was to assess the reliability of specific physiological, psychological, and cognitive variables in 31 chronic fatigue syndrome (CFS) subjects and 31 matched control subjects. All variables were assessed weekly over a 4-week period and reliability was determined using an intraclass correlation coefficient (ICC). Results ranged from moderately to highly reliable for all variables assessed, except for mental and physical fatigue, which were of questionable reliability in both groups (ICC = 0.61 and 0.65, respectively, for the CFS group; 0.62 and 0.52 for the control group).

A Pearson product-moment correlation analysis that compared exercise performance with all psychological variables assessed, demonstrated a significant relationship between exercise performance and depression (r = .41, P = .02) in week 3 only, suggesting minimal association between objective performance and psychological responses. These correlation results support a central, as opposed to a peripheral, basis to the sensation of fatigue in CFS.

 

Source: Wallman KE, Morton AR, Goodman C, Grove R. Reliability of physiological, psychological, and cognitive variables in chronic fatigue syndrome. Res Sports Med. 2005 Jul-Sep;13(3):231-41. http://www.ncbi.nlm.nih.gov/pubmed/16392538

 

Orthostatic instability in a population-based study of chronic fatigue syndrome

Abstract:

PURPOSE: Autonomic nervous system dysfunction has been suggested as involved in the pathophysiology of chronic fatigue syndrome. This population-based case control study addressed the potential association between orthostatic instability (one sign of dysautonomia) and chronic fatigue syndrome.

SUBJECTS AND METHODS: Fifty-eight subjects who fulfilled criteria of the 1994 chronic fatigue syndrome research case definition and 55 healthy controls participated in a 2-day inpatient evaluation. Subjects had been identified during a 4-year population-based chronic fatigue syndrome surveillance study in Wichita, Kan. The present study evaluated subjects’ current medical and psychiatric status, reviewed past medical/psychiatric history and medication use, used a stand-up test to screen for orthostatic instability, and conducted a head-up tilt table test to diagnose orthostatic instability.

RESULTS: No one manifested orthostatic instability in the stand-up test. The head-up tilt test elicited orthostatic instability in 30% of eligible chronic fatigue syndrome subjects (all with postural orthostatic tachycardia) and 48% of controls (50% with neurally mediated hypotension); intolerance was present in only nonfatigued (n=7) subjects. Neither fatigue nor illness severity were associated with outcome.

CONCLUSIONS: Orthostatic instability was similar in persons with chronic fatigue syndrome and nonfatigued controls subjects recruited from the general Wichita population. Delayed responses to head-up tilt tests were common and may reflect hydration status. These findings suggest reappraisal of primary dysautonomia as a factor in the pathogenesis of chronic fatigue syndrome.

Comment in: Orthostatic intolerance in chronic fatigue syndrome. [Am J Med. 2007]

 

Source: Jones JF, Nicholson A, Nisenbaum R, Papanicolaou DA, Solomon L, Boneva R, Heim C, Reeves WC. Orthostatic instability in a population-based study of chronic fatigue syndrome. Am J Med. 2005 Dec;118(12):1415. http://www.ncbi.nlm.nih.gov/pubmed/16378795

 

Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome

Abstract:

We assessed the serotonin status of patients with the chronic fatigue syndrome (CFS). Tryptophan (Trp) availability to the brain, expressed as the ratio of concentration of serum Trp to the sum of those of its five competitors (CAA), and other parameters of Trp disposition were compared in 23 patients with the CFS and 42 healthy controls.

The serum [free Trp]/[CAA] ratio was 43% higher in CFS patients, due to a 48% higher [free Trp]. [Total Trp] was also significantly higher (by 19%) in CFS patients, and, although the [total Trp]/[CAA] ratio did not differ significantly between the control and patient groups, the difference became significant when the results were co-varied with age and gender. [CAA] was not significantly different between groups, but was significantly lower in females, compared to males, of the CFS patient group.

We have established normal ranges for Trp disposition parameters and propose criteria for defining the serotonin-biosynthetic status in humans. We have provisionally identified two subgroups of CFS patients, one with normal serotonin and the other with a high serotonin status. The relevance of our findings to, and their implications for, the pharmacological and other therapies of the chronic fatigue syndrome are discussed.

 

Source: Badawy AA, Morgan CJ, Llewelyn MB, Albuquerque SR, Farmer A. Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome. J Psychopharmacol. 2005 Jul;19(4):385-91. http://www.ncbi.nlm.nih.gov/pubmed/15982993

 

Gray matter volume reduction in the chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities.

We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high-resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities.

We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.

 

Source: de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I. Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage. 2005 Jul 1;26(3):777-81. Epub 2005 Apr 7. http://www.ncbi.nlm.nih.gov/pubmed/15955487

 

Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635

Abstract:

BACKGROUND: Research from neuroendocrine challenge and other indirect studies has suggested increased central 5-HT function in chronic fatigue syndrome (CFS) and increased 5-HT1A receptor sensitivity. We assessed brain 5-HT1A receptor binding potential directly using the specific radioligand [11C]WAY-100635 and positron emission tomography (PET).

METHODS: We selected 10 patients from a tertiary referral clinic who fulfilled the CDC consensus criteria for CFS. To assemble a homogenous group and avoid confounding effects, we enrolled only subjects who were completely medication-free and did not have current comorbid psychiatric illness. We also scanned 10 healthy control subjects.

RESULTS: There was a widespread reduction in 5-HT1A receptor binding potential in CFS relative to control subjects. This was particularly marked in the hippocampus bilaterally, where a 23% reduction was observed.

CONCLUSIONS: There is evidence of decreased 5-HT1A receptor number or affinity in CFS. This may be a primary feature of CFS, related to the underlying pathophysiology, or a finding secondary to other processes, such as previous depression, other biological changes or the behavioral consequences of CFS.

 

Source: Cleare AJ, Messa C, Rabiner EA, Grasby PM. Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635. Biol Psychiatry. 2005 Feb 1;57(3):239-46. http://www.ncbi.nlm.nih.gov/pubmed/15691524

 

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)

 

Reduction of serotonin transporters of patients with chronic fatigue syndrome

Abstract:

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET).

Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients.

Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

 

Source: Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004 Dec 3;15(17):2571-4. http://www.ncbi.nlm.nih.gov/pubmed/15570154

 

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Abstract:

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.

METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects.

RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects.

CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.

 

Source: Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N. Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol. 2004 Oct 4;4(1):14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524491/

 

Altered central nervous system signal during motor performance in chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of this study was to determine whether brain activity of chronic fatigue syndrome (CFS) patients during voluntary motor actions differs from that of healthy individuals.

METHODS: Eight CFS patients and 8 age- and gender-matched healthy volunteers performed isometric handgrip contractions at 50% maximal voluntary contraction level. They first performed 50 contractions with a 10 s rest between adjacent trials–‘Non-Fatigue’ (NFT) task. Subsequently, the same number of contractions was performed with only a 5 s rest between trials–‘Fatigue’ (FT) task. Fifty-eight channels of surface EEG were recorded simultaneously from the scalp. Spectrum analysis was performed to estimate power of EEG frequency in different tasks. Motor activity-related cortical potential (MRCP) was derived by triggered averaging of EEG signals associated with the muscle contractions.

RESULTS: Major findings include: (i) Motor performance of the CFS patients was poorer than the controls. (ii) Relative power of EEG theta frequency band (4-8 Hz) during performing the NFT and FT tasks was significantly greater in the CFS than control group (P < 0.05). (iii) The amplitude of MRCP negative potential (NP) for the combined NFT and FT tasks was higher in the CFS than control group (P < 0.05) (iv) Within the CFS group, the NP was greater for the FT than NFT task (P<0.01), whereas no such difference between the two tasks was found in the control group.

CONCLUSIONS: These results clearly show that CFS involves altered central nervous system signals in controlling voluntary muscle activities, especially when the activities induce fatigue.

SIGNIFICANCE: Physical activity-induced EEG signal changes may serve as physiological markers for more objective diagnosis of CFS.

 

Source: Siemionow V, Fang Y, Calabrese L, Sahgal V, Yue GH. Altered central nervous system signal during motor performance in chronic fatigue syndrome. Clin Neurophysiol. 2004 Oct;115(10):2372-81. http://www.ncbi.nlm.nih.gov/pubmed/15351380