Category: Neurology

Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome

Abstract:

MRI has previously provided conflicting results when used to search for brain abnormalities in sufferers of chronic fatigue syndrome (CFS). Eighteen CFS patients and nine healthy volunteers each underwent MRI on two occasions, one year apart. The resulting images were examined for abnormalities in brain atrophy, deep white matter hyperintensities (WMH) and cerebral blood and cerebrospinal fluid (CSF) flow.

Mean proportionate CSF volume was not significantly different between subject groups. All participants showed a slight increase in CSF between scans, but no significant difference was found between those with CFS and those without. Between-group comparisons of ventricular volume revealed no significant differences at study commencement and no significant change over the year. No significant inter-group differences were found for any of the cerebral blood and CSF flow parameters. Low levels of WMH were found in all participants. Objective scoring of WMH using Scheltens’ scale revealed no change in summary components (prosencephalic deep white matter hyperintensities, basal ganglia hyperintensities and infratentorial hyperintensities) or in individual component variables between the baseline and 1 year follow-up scans. No abnormal patterns in rate and extent of brain atrophy, ventricle volume, white matter lesions, cerebral blood flow or aqueductal CSF flow were detected in the CFS population.

These results throw open the debate into whether MRI scanning can reveal diagnostic signs of CFS and clinically questions the diagnoses of CFS made on the basis of previous research conclusions.

 

Source: Perrin R, Embleton K, Pentreath VW, Jackson A. Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome. Br J Radiol. 2010 May;83(989):419-23. doi: 10.1259/bjr/85621779. Epub 2010 Mar 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473570/ (Full article)

 

EEG source analysis of chronic fatigue syndrome

Abstract:

Sixty-one dextral, unmedicated women with chronic fatigue syndrome (CFS) diagnosed according to the Fukuda criteria (1994) and referred for investigation by rheumatologists and internists were studied with quantitative EEG (43 channels) at rest with eyes open and during verbal and spatial cognitive activation. The EEGs from the patients were compared with recordings from 80 dextral healthy female controls. Only those subjects who could provide 20 1-s artefact-free segments of EEG were admitted into the study.

The analysis consisted of the identification of the spatial patterns in the EEGs that maximally differentiated the two groups and the estimation of the cortical source distributions underlying these patterns. Spatial patterns were analyzed in the alpha (8-13Hz) and beta (14-20Hz) bands and the source distributions were estimated using the Borgiotti-Kaplan BEAMFORMER algorithm.

The results indicate that the spatial patterns identified were effective in separating the two groups, providing a minimum correct retrospective classification rate of 72% in both frequency bands while the subjects were at rest to a maximum of 83% in the alpha band during the verbal cognitive condition.

Underlying cortical source distributions showed significant differences between the two groups in both frequency bands and in all cognitive conditions. Lateralized cortical differences were evident between the two groups in the both frequency bands during both the verbal and spatial cognitive conditions. During these active cognitive conditions, the CFS group showed significantly greater source-current activity than the controls in the left frontal-temporal-parietal regions of the cortex.

Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

 

Source: Flor-Henry P, Lind JC, Koles ZJ. EEG source analysis of chronic fatigue syndrome. Psychiatry Res. 2010 Feb 28;181(2):155-64. doi: 10.1016/j.pscychresns.2009.10.007. Epub 2009 Dec 16. https://www.ncbi.nlm.nih.gov/pubmed/20006474

 

Lower ambulatory blood pressure in chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine blood pressure circadian rhythm in subjects with chronic fatigue syndrome (CFS) and appropriate normal and fatigued controls to correlate parameters of blood pressure regulation with perception of fatigue in an observational cohort study. The cause of CFS remains unknown and there are no effective treatments.

METHODS: To address whether inactivity was a confounder, we performed a 24-hour ambulatory blood pressure monitoring in the following three subject groups: 1) CFS patients (Fukuda Diagnostic criteria) (n = 38); 2) normal controls (n = 120); and 3) a fatigue comparison group (n = 47) with the autoimmune liver disease primary biliary cirrhosis (PBC). All patients completed a measure of fatigue severity (Fatigue Impact Scale). In view of the different demographics between the patient groups, patients were age- and sex-matched on a case-by-case basis to normal controls and blood pressure parameters were compared.

RESULTS: Compared with the control population, the CFS group had significantly lower systolic blood pressure (p < .0001) and mean arterial blood pressure (p = .0002) and exaggerated diurnal variation (p = .009). There was a significant inverse relationship between increasing fatigue and diurnal variation of blood pressure in both the CFS and PBC groups (p < .05).

CONCLUSION: Lower blood pressure and abnormal diurnal blood pressure regulation occur in patients with CFS. We would suggest the need for a randomized, placebo-controlled trial of agents to increase blood pressure such as midodrine in CFS patients with an autonomic phenotype.

 

Source: Newton JL, Sheth A, Shin J, Pairman J, Wilton K, Burt JA, Jones DE. Lower ambulatory blood pressure in chronic fatigue syndrome. Psychosom Med. 2009 Apr;71(3):361-5. doi: 10.1097/PSY.0b013e31819ccd2a. Epub 2009 Mar 17. https://www.ncbi.nlm.nih.gov/pubmed/19297309

 

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study

Abstract:

Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ.

Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate.

CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

 

Source: Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC. Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed. 2009 Apr;22(3):251-8. doi: 10.1002/nbm.1315. https://www.ncbi.nlm.nih.gov/pubmed/18942064

 

Chronic fatigue syndrome and the central nervous system

Abstract:

An increasing amount of neuroimaging evidence supports the hypothesis that chronic fatigue syndrome patients have structural or functional abnormalities within the brain. Moreover, some neurotrophic factors, neurotransmitters and cytokines have also been evaluated in order to elucidate the mechanism of abnormal neuropsychic findings in chronic fatigue syndrome. In this review, we suggest that the focal point of chronic fatigue syndrome research should be transferred to the central nervous system.

 

Source: Chen R, Liang FX, Moriya J, Yamakawa J, Sumino H, Kanda T, Takahashi T. Chronic fatigue syndrome and the central nervous system. J Int Med Res. 2008 Sep-Oct;36(5):867-74. https://www.ncbi.nlm.nih.gov/pubmed/18831878

 

Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study

Abstract:

BACKGROUND: Studies comparing chronic fatigue syndrome (CFS) and major depressive disorder (MDD) reported similarities as well as differences between the two disorders. However, whereas psychomotor symptoms have been studied extensively in MDD, such research in CFS is more limited. Moreover, the few studies that compared cognitive and motor performance in MDD and CFS yielded inconsistent results. This study hence directly compares fine psychomotor functioning in both syndromes.

METHODS: Thirty-eight patients diagnosed with CFS without a current major depressive episode (MDE), 32 MDD patients with a current MDE and 38 healthy controls performed two computerized copying tasks differing in complexity: a line-copying task that mainly requires motor effort and a figure-copying task requiring additional cognitive efforts. All participants were female. A multivariate general linear model was used to compute group differences.

RESULT: Overall, both patient groups performed more slowly than the controls. Compared to CFS patients, patients with MDD needed significantly more time to copy the single lines but no such between-group performance difference was observed for the figure reproductions. In this latter copying task, the increasing complexity of the figures resulted in prolonged reaction times for all three participant groups with the effect being larger and the magnitude similar for the two patient groups.

LIMITATIONS: All patients were female and most were on psychotropic medication.

CONCLUSIONS: Both the MDD and CFS patients tested demonstrated an overall fine motor slowing, with the motor component being more affected in the MDD patients than in the CFS patients while both patient groups showed similar cognitive impairments.

 

Source: Schrijvers D, Van Den Eede F, Maas Y, Cosyns P, Hulstijn W, Sabbe BG. Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study. J Affect Disord. 2009 May;115(1-2):46-53. doi: 10.1016/j.jad.2008.08.010. Epub 2008 Sep 24. https://www.ncbi.nlm.nih.gov/pubmed/18817977

 

Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome

Abstract:

BACKGROUND: It has been suggested that postural orthostatic tachycardia syndrome (POTS) be considered in the differential diagnosis of those with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Currently, measurement of haemodynamic response to standing is not recommended in the UK NICE CFS/ME guidelines.

OBJECTIVES: To determine prevalence of POTS in patients with CFS/ME.

DESIGN: Observational cohort study.

METHODS: Fifty-nine patients with CFS/ME (Fukuda criteria) and 52 age- and sex-matched controls underwent formal autonomic assessment in the cardiovascular laboratory with continuous heart rate and beat-to-beat blood pressure measurement (Task Force, CNSystems, Graz Austria). Haemodynamic responses to standing over 2 min were measured. POTS was defined as symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of >30 beats per minute or to a heart rate of >120 beats per minute on standing.

RESULTS: Maximum heart rate on standing was significantly higher in the CFS/ME group compared with controls (106 +/- 20 vs. 98 +/- 13; P = 0.02). Of the CFS/ME group, 27% (16/59) had POTS compared with 9% (5) in the control population (P = 0.006). This difference was predominantly related to the increased proportion of those in the CFS/ME group whose heart rate increased to >120 beats per minute on standing (P = 0.0002). Increasing fatigue was associated with increase in heart rate (P = 0.04; r(2) = 0.1).

CONCLUSION: POTS is a frequent finding in patients with CFS/ME. We suggest that clinical evaluation of patients with CFS/ME should include response to standing. Studies are needed to determine the optimum intervention strategy to manage POTS in those with CFS/ME.

 

Source: Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Dec;101(12):961-5. doi: 10.1093/qjmed/hcn123. Epub 2008 Sep 19. http://qjmed.oxfordjournals.org/content/101/12/961.long (Full article)

 

Can CBT substantially change grey matter volume in chronic fatigue syndrome?

Sir, I wish to comment on the paper ‘Increase in prefrontal cortical volume following cognitive behavioural therapy (CBT) in patients with chronic fatigue syndrome (CFS)’ (De Lange et al., 2008). The authors compared the grey matter volume (GMV) of 22 patients with CFS before and after treatment with CBT, and with 22 healthy controls who were assessed at a similar time interval but received no treatment. The patient sample at baseline had a 5% smaller GMV as compared to healthy controls. In patients, GMV at baseline was correlated with slow information processing speed and physical activity. At follow-up, in the patient group, mean GMV increased with 0.7% from 669.4 to 674.1 ml. This increase in GMV was correlated with changes in cognitive speed. On the basis of this result, the authors conclude ‘that the cerebral atrophy associated with CFS is partially reversed after effective CBT’. In the Netherlands, a press release of the author’s institution even states ‘CBT brings about structural changes in brains of patients’ (Radboud University, 2008). The question arises whether the study results indeed support such far reaching conclusions.

Two critical points need to be taken into consideration. First, the authors did not include a control group of patients receiving no treatment or a different treatment. Therefore, the increase in GMV cannot be attributed to the CBT treatment given. It is possible that the natural course of and fluctuations in the illness are responsible for this result. In addition, it might be possible that other treatments than CBT would have resulted in the same, or even better, results. Second, even if the results were indeed to be attributed to changes in lifestyle brought about by CBT, several questions still remain. To name a few, first, the increase in volume of <1% is very modest. Therefore, the question is whether, although statistically significant, this small increase is also of clinical significance. Second, if CBT brings about changes in lifestyle, and these changes are responsible for small improvements in the patients’ brain and activity levels, are these changes structural and related to the primary disease process? An alternative interpretation is that changing the lifestyle of patients, influences their quality of life, activity patterns and GMV, while the underlying disease process is not influenced.

Another critical remark relates to the fact that the authors in their paper do not mention the proportion of absolute increase in GMV of 0.7%, but rather report that the initial between-group difference between patients and healthy controls decreases with 12%. For readers, it is important to realize that the measure of change reported by the authors is influenced by the absolute size of the between-group difference: the smaller, and therefore less relevant, this difference is, the larger the reported proportion becomes, thereby making less relevant results looking more impressive.

The above considerations lead to the conclusion, that the author’s results, although interesting, do not support the far reaching conclusions regarding the power of CBT.

You can read the rest of this comment here: http://brain.oxfordjournals.org/content/132/6/e110.long

Comment in: Change in grey matter volume cannot be assumed to be due to cognitive behavioural therapy. [Brain. 2009]

Comment on: Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. [Brain. 2008]

 

Source: Bramsen I. Can CBT substantially change grey matter volume in chronic fatigue syndrome? Brain. 2009 Jun;132(Pt 6):e110; author reply e111. doi: 10.1093/brain/awn207. Epub 2008 Aug 29. http://brain.oxfordjournals.org/content/132/6/e110.long (Full article)

 

Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study

Abstract:

Deficient endogenous pain inhibition, e.g. Diffuse noxious inhibitory controls (DNIC), or hormonal abnormalities like hypocortisolism, could be responsible for chronic widespread pain in Chronic Fatigue Syndrome (CFS). Thirty-one CFS-patients with chronic pain and 31 healthy controls were subjected to spatial summation of thermal noxious stimuli by gradual immersion (ascending or descending) of the arm in warm water (46 degrees C). They rated pain intensity every 15s. Every immersion took 2 min, alternated with 5 min rest. Before and after immersion, salivary cortisol was assessed.

Overall pain ratings were higher in CFS-patients, but the evolution was not different between patients and controls, during both ascending and descending immersion. Pain intensity and immersed surface were only correlated during the descending session in both patients (r=.334) and controls (r=.346). When comparing the first and the last 15s of every emersion, it was found that pain inhibition starts slower for CFS-patients in comparison to healthy subjects. Both pre- or post-values and cortisol response did not differ between controls and patients. The drop in cortisol was significantly correlated to pain intensity in CFS (r between .357 and .402).

In addition to the hyperalgesia in CFS, DNIC react slower to spatial summation of thermal noxious stimuli. We found no evidence for hypocortisolism in CFS, and the cortisol response to nociception was not different in CFS compared to healthy subjects. In conclusion, delayed pain inhibition may play a role in chronic widespread pain in CFS but further research is required.

 

Source: Meeus M, Nijs J, Van de Wauwer N, Toeback L, Truijen S. Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study. Pain. 2008 Oct 15;139(2):439-48. doi: 10.1016/j.pain.2008.05.018. Epub 2008 Jul 9. https://www.ncbi.nlm.nih.gov/pubmed/18617327

 

Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery.

Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy control participants. CBT intervention led to a significant improvement in health status, physical activity and cognitive performance. Crucially, CFS patients showed a significant increase in grey matter volume, localized in the lateral prefrontal cortex. This change in cerebral volume was related to improvements in cognitive speed in the CFS patients.

Our findings indicate that the cerebral atrophy associated with CFS is partially reversed after effective CBT. This result provides an example of macroscopic cortical plasticity in the adult human brain, demonstrating a surprisingly dynamic relation between behavioural state and cerebral anatomy. Furthermore, our results reveal a possible neurobiological substrate of psychotherapeutic treatment.

Comment in: Can CBT substantially change grey matter volume in chronic fatigue syndrome? [Brain. 2009]

 

Source: de Lange FP1, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I. Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. Brain. 2008 Aug;131(Pt 8):2172-80. doi: 10.1093/brain/awn140. Epub 2008 Jun 28. http://brain.oxfordjournals.org/content/131/8/2172.long (Full article)