Tag: brain

Neural correlates of the chronic fatigue syndrome–an fMRI study

Abstract:

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS.

We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups.

Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error.

Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

 

Source: de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, Toni I. Neural correlates of the chronic fatigue syndrome–an fMRI study. Brain. 2004 Sep;127(Pt 9):1948-57. Epub 2004 Jul 7. http://brain.oxfordjournals.org/content/127/9/1948.long (Full article)

 

Eicosapentaenoic acid-rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes

Abstract:

Lateral ventricular enlargement has been reported in chronic fatigue syndrome, while cerebral neurospectroscopy has recently indicated that essential fatty acid treatment may be of value in this condition. An essential fatty acid supplement rich in eicosapentaenoic acid (EPA) was therefore given daily to a female patient with a 6-year history of unremitting symptoms of chronic fatigue syndrome.

Cerebral magnetic resonance scanning was carried out at baseline and 16 weeks later. The EPA-rich essential fatty acid supplementation led to a marked clinical improvement in her symptoms of chronic fatigue syndrome, starting within 6-8 weeks. Accurate quantification of the lateral ventricular volumes in the baseline and 16-week follow-up registered images of high-resolution magnetic resonance imaging structural scans showed that the treatment was accompanied by a marked reduction in the lateral ventricular volume during this period, from 28,940-23,660 mm3.

 

Source: Puri BK, Holmes J, Hamilton G. Eicosapentaenoic acid-rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes.  Int J Clin Pract. 2004 Mar;58(3):297-9. http://www.ncbi.nlm.nih.gov/pubmed/15117099

 

Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To evaluate cerebral glucose metabolism, assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with chronic fatigue syndrome (CFS), using an observer independent analytical approach; and to characterise any observed alterations by correlating them with neuropsychological deficits.

METHODS: 26 patients (13 female, 13 male) were examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent extensive psychometric testing including the hospital anxiety and depression scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG-PET was done in all the subjects. After stereotactic normalisation, single subject comparisons with an age and sex matched normal database (n = 18) and a group comparison between the patients and normal controls were undertaken, along with additional correlation analyses between brain metabolism and psychometric test scores.

RESULTS: 12 of the 26 patients showed no significant decrease in FDG uptake compared with the controls. Of the remaining 14, 12 showed hypometabolism bilaterally in the cingulate gyrus and the adjacent mesial cortical areas. Five of these 12 patients also had decreased metabolism in the orbitofrontal cortex. The two remaining patients had hypometabolism in the cuneus/praecuneus. Correlation analyses showed significant correlations between some test scores (anxiety, depression, health related quality of life) but not fatigue and regional reductions in glucose metabolism.

CONCLUSIONS: Although abnormalities in FDG-PET were only detectable in approximately half the CFS patients examined, and no specific pattern for CFS could be identified, PET may provide valuable information in helping to separate CFS patients into subpopulations with and without apparent alterations in the central nervous system.

 

Source: Siessmeier T, Nix WA, Hardt J, Schreckenberger M, Egle UT, Bartenstein P. Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):922-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1738575/ (Full article)

 

 

Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterised by fatigue and musculosketetal pain, the severity of which is variable. Simple reaction times (SRTs) and movement times (SMTs) are slowed in CFS. Our objective is to correlate the day-to-day changes in symptomatology with any change in SRT, SMT or corticospinal excitability.

Ten CFS patients were tested on two occasions up to two years apart. Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the thenar muscles. Threshold TMS strength to evoke MEPs was measured to index corticospinal excitability. SRTs and SMTs were measured.

The percentage change in both SRTs and SMTs between the two test sessions correlated with the percentage change in corticospinal excitability assessed according to threshold TMS intensity required to produce MEPs. This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of SRTs supports the notion of a deficit in motor preparatory areas of the brain.

 

Source: Davey NJ, Puri BK, Catley M, Main J, Nowicky AV, Zaman R. Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome. Int J Clin Pract. 2003 May;57(4):262-4. http://www.ncbi.nlm.nih.gov/pubmed/12800454

 

Hypothalamic digoxin, cerebral chemical dominance and myalgic encephalomyelitis

Abstract:

The isoprenoid pathway was assessed in 15 patients with chronic fatigue syndrome. The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance had any correlation with these disease states.

The isoprenoid metabolites–digoxin, dolichol, and ubiquinone–RBC membrane Na+-K+ ATPase activity, serum magnesium and tyrosine/tryptophan catabolic patterns were assessed. The free-radical metabolism, glycoconjugate metabolism, and RBC membrane composition was also assessed. Membrane Na+-K+ ATPase activity and serum magnesium levels were decreased while HMG CoA reductase activity and serum digoxin levels were increased in myalgic encephalomyelitis (ME). There were increased levels of tryptophan catabolites–nicotine, strychnine, quinolinic acid, and serotonin–and decreased levels of tyrosine catabolites–dopamine, noradrenaline, and morphine in ME. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual GAG fractions, and lysosomal enzymes in ME. Reduced levels of ubiquinone, reduced glutathione, and free-radical scavenging enzymes, as well as increased lipid peroxidation products and nitric oxide, were noticed in ME.

The biochemical patterns in ME correlated with those obtained in right hemispheric chemical dominance. The role of hypothalamic digoxin and neurotransmitter induced immune activation, altered glycoconjugate metabolism, and resultant defective viral antigen presentation, NMDA excitotoxicity and cognitive dysfunction, and mitochondrial dysfunction related myalgia in the pathogenesis of ME is stressed. ME occurs in individuals with right hemispheric chemical dominance.

 

Source: Kurup RK, Kurup PA. Hypothalamic digoxin, cerebral chemical dominance and myalgic encephalomyelitis. Int J Neurosci. 2003 May;113(5):683-701. https://ammes.orgwp-admin/post-new.php

 

Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome

Abstract:

Fatigue is a common symptom of neurological diseases that affect basal ganglia function. We used proton magnetic resonance spectroscopy ((1)H MRS) to study the metabolic functions of the basal ganglia in chronic fatigue syndrome (CFS) to test the hypothesis that fatigue in CFS may have a neurogenic component. (1)H MRS of left basal ganglia was carried out in eight non-psychiatric patients with CFS and their results were compared to age- and sex-matched healthy asymptomatic healthy controls. A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group (p < 0.001). In the absence of regional structural or inflammatory pathology, increased choline resonance in CFS may be an indicator of higher cell membrane turnover due to gliosis or altered intramembrane signalling.

 

Source: Chaudhuri A, Condon BR, Gow JW, Brennan D, Hadley DM. Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Neuroreport. 2003 Feb 10;14(2):225-8. http://www.ncbi.nlm.nih.gov/pubmed/12598734

 

Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome

Erratum in: Psychosom Med. 2003 Mar-Apr;65(2):210.

 

Abstract:

OBJECTIVE: The purposes of this study were to compare functional imaging under control and experimental conditions among patients with chronic fatigue syndrome (CFS) and healthy persons and to examine perceived and objective performance on a test of attention and working memory previously found to be difficult for persons with CFS.

METHODS: Single-photon emission computerized tomography scans were completed on 15 subjects with CFS and 15 healthy persons twice: at rest and when performing the Paced Auditory Serial Addition Test (PASAT).

RESULTS: No group differences were found for performance on the PASAT despite CFS subjects’ perceptions of exerting more mental effort to perform the task than healthy subjects. Inspection of the aggregate scans by group and task suggested a pattern of diffuse regional cerebral blood flow among subjects with CFS in comparison with the more focal pattern of regional cerebral blood flow seen among healthy subjects. Between-group region-of-interest analysis revealed that although CFS subjects showed less perfusion in the anterior cingulate region, the change in CFS subjects’ activation of the left anterior cingulate region during the PASAT was greater than that observed for healthy subjects. The differences were not attributable to lesser effort by the subjects with CFS, confounding effects of mood perturbation, or to poorer performance on the experimental task.

CONCLUSIONS: Further research regarding CFS subjects’ diffuse cerebral perfusion and its relationship to inefficient neuropsychological performance is warranted.

 

Source: Schmaling KB, Lewis DH, Fiedelak JI, Mahurin R, Buchwald DS. Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome. Psychosom Med. 2003 Jan-Feb;65(1):129-36. http://www.ncbi.nlm.nih.gov/pubmed/12554824

 

Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain

Abstract:

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation.

Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate.

When we studied the cerebral uptake of acetylcarnitine by using [2-(11)C]acetyl-L-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann’s area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum.

These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

 

Source: Kuratsune H, Yamaguti K, Lindh G, Evengård B, Hagberg G, Matsumura K, Iwase M, Onoe H, Takahashi M, Machii T, Kanakura Y, Kitani T, Långström B, Watanabe Y. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage. 2002 Nov;17(3):1256-65. http://www.ncbi.nlm.nih.gov/pubmed/12414265

 

Relative increase in choline in the occipital cortex in chronic fatigue syndrome

Abstract:

OBJECTIVE: To test the hypothesis that chronic fatigue syndrome (CFS) is associated with altered cerebral metabolites in the frontal and occipital cortices.

METHOD: Cerebral proton magnetic resonance spectroscopy (1H MRS) was carried out in eight CFS patients and eight age- and sex-matched healthy control subjects. Spectra were obtained from 20 x 20 x 20 mm3 voxels in the dominant motor and occipital cortices using a point-resolved spectroscopy pulse sequence.

RESULTS: The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No other metabolite ratios were significantly different between the two groups in either the frontal or occipital cortex. In addition, there was a loss of the normal spatial variation of Cho in CFS.

CONCLUSION: Our results suggest that there may be an abnormality of phospholipid metabolism in the brain in CFS.

 

Source: Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, Davey NJ. Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand. 2002 Sep;106(3):224-6. http://www.ncbi.nlm.nih.gov/pubmed/12197861

 

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