Tag: brain

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

 

Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome

Abstract:

Seven patients with chronic fatigue syndrome (CFS) were matched with ten healthy control subjects of similar age. Hippocampal volume, obtained from magnetic resonance images using an unbiased method, showed no difference between the two groups, whereas proton magnetic resonance spectroscopy showed a significantly reduced concentration of N-acetylaspartate in the right hippocampus of CFS patients (p = 0.005).

Source: Brooks JC, Roberts N, Whitehouse G, Majeed T. Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome. Br J Radiol. 2000 Nov;73(875):1206-8. http://www.ncbi.nlm.nih.gov/pubmed/11144799

The role of tryptophan in fatigue in different conditions of stress

Abstract:

Tryptophan is the precursor for the neurotransmitter 5-hydroxytryptamine (5-HT), which is involved in fatigue and sleep. It is present in bound and free from in the blood, where the concentration is controlled by albumin binding to tryptophan. An increase in plasma free tryptophan leads to an increased rate of entry of tryptophan into the brain. This should lead to a higher level of 5-HT which may cause central fatigue. Central fatigue is implicated in clinical conditions such as chronic fatigue syndrome and post-operative fatigue. Increased plasma free tryptophan leads to an increase in the plasma concentration ratio of free tryptophan to the branched chain amino acids (BCAA) which compete with tryptophan for entry into the brain across the blood-brain barrier.

The plasma concentrations of these amino acids were measured in chronic fatigue syndrome patients (CFS) before and after exercise (Castell et al., 1998), and in patients undergoing major surgery (Yamamoto et al., 1997). In the CFS patients, the pre-exercise concentration of plasma free tryptophan was higher than in controls (p < 0.05) but did not change during or after exercise. This might indicate an abnormally high level of brain 5-HT in CFS patients leading to persistent fatigue.

In the control group, plasma free tryptophan was increased after maximal exercise (p < 0.001), returning towards baseline levels 60 min later. The apparent failure of the CFS patients to change the plasma free tryptophan concentration or the free tryptophan/BCAA ratio during exercise may indicate increased sensitivity of brain 5-HT receptors, as has been demonstrated in other studies (Cleare et al., 1995).

In post-operative recovery after major surgery plasma free tryptophan concentrations were markedly increased compared with baseline levels; the plasma free tryptophan/BCAA concentration ratio was also increased after surgery. Plasma albumin concentrations were decreased after surgery: this may account for the increase in plasma free tryptophan levels.

Provision of BCAA has improved mental performance in athletes after endurance exercise (Blomstrand et al., 1995, 1997). It is suggested that BCAA supplementation may help to counteract the effects of an increase in plasma free tryptophan, and may thus improve the status of patients during or after some clinically stressful conditions.

 

Source: Castell LM, Yamamoto T, Phoenix J, Newsholme EA. The role of tryptophan in fatigue in different conditions of stress. Adv Exp Med Biol. 1999;467:697-704. http://www.ncbi.nlm.nih.gov/pubmed/10721121

 

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology.

We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated.

Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

 

Source: Abu-Judeh HH, Levine S, Kumar M, el-Zeftawy H, Naddaf S, Lou JQ, Abdel-Dayem HM. Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Nucl Med Commun. 1998 Nov;19(11):1065-71. http://www.ncbi.nlm.nih.gov/pubmed/9861623