Neurology – Page 18 – American ME and CFS Society

Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms

Abstract:

BACKGROUND: The pathophysiology of chronic fatigue syndrome (CFS) in adolescents is unknown, and the clinical course and prognosis is still questioned. Recent research indicates that abnormalities of autonomic cardiovascular control may play an important role. The aim of this research project was to perform a follow-up study of adolescents with chronic fatigue syndrome, focusing on clinical symptoms and autonomic cardiovascular control.

METHODS: 47 adolescents (12-18 years old) with CFS were recruited from the outpatient clinic at the Department of Pediatrics, Oslo University Hospital. In a primary visit and a follow-up visit (3-17 months later), we evaluated: a) a wide range of complaints and symptoms and b) cardiovascular variables at baseline and during a 20° head-up tilt-test (HUT).

RESULTS: At the second visit, patients reported significant improvement regarding functional impairments, fatigue severity, muscular pain, concentration problems, post-exertional malaise and the problem of non-relieving rest. Also, at the second visit, baseline heart rate (HR), blood pressure, total peripheral resistance index (TPRI) and LF/HF (low-frequency:high-frequency heart rate variability ratio, an index of sinus node sympathovagal balance derived from spectral analyses of heart rate) were significant lower, and the increases in HR, mean blood pressure (MBP), diastolic blood pressure (DBP) and TPRI during tilt were significantly less pronounced as compared to the first visit. There was a significant correlation between changes in autonomic symptom score, fatigue severity score and functional impairment score from the first to the second visit.

CONCLUSIONS: The majority of adolescents with CFS experienced an improvement over time in functional impairment, self-reported fatigue and additional symptoms, and a concurrent improvement of autonomic cardiovascular control. A possible connection between clinical symptoms and abnormal autonomic control in CFS might represent a focus for further research.

Source: Sulheim D, Hurum H, Helland IB, Thaulow E, Wyller VB. Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms. Biopsychosoc Med. 2012 Mar 21;6:10. doi: 10.1186/1751-0759-6-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337799/ (Full article)

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

Abstract:

Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed. The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue. In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing.

Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°). Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis.

A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002).

There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05). Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%.

Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls.

Source: Allen J, Murray A, Di Maria C, Newton JL. Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker. Physiol Meas. 2012 Feb;33(2):231-41. doi: 10.1088/0967-3334/33/2/231. Epub 2012 Jan 25. https://www.ncbi.nlm.nih.gov/pubmed/22273713

Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study

Abstract:

OBJECTIVE: It is not established whether myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is associated with structural brain changes. The aim of this study was to investigate this by conducting the largest voxel-based morphometry study to date in CFS.

METHODS: High-resolution structural 3 T cerebral MRI scanning was carried out in 26 patients with CFS and 26 age- and gender-matched healthy volunteers. Voxel-wise generalised linear modelling was applied to the processed MR data using permutation-based non-parametric testing, forming clusters at t>2.3 and testing clusters for significance at p<0.05, corrected for multiple comparisons across space.

RESULTS: Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced grey matter volume in the CFS group were noted in the occipital lobes (right and left occipital poles; left lateral occipital cortex, superior division; and left supracalcrine cortex), the right angular gyrus and the posterior division of the left parahippocampal gyrus. Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced white matter volume in the CFS group were also noted in the left occipital lobe.

CONCLUSION: These data support the hypothesis that significant neuroanatomical changes occur in CFS, and are consistent with the complaint of impaired memory that is common in this illness; they also suggest that subtle abnormalities in visual processing, and discrepancies between intended actions and consequent movements, may occur in CFS.

Source: Puri BK, Jakeman PM, Agour M, Gunatilake KD, Fernando KA, Gurusinghe AI, Treasaden IH, Waldman AD, Gishen P. Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study. Br J Radiol. 2012 Jul;85(1015):e270-3. doi: 10.1259/bjr/93889091. Epub 2011 Nov 29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474083/ (Full article)

Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome

Abstract:

The weight of current evidence supports the presence of the following factors related to hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS): mild hypocortisolism; attenuated diurnal variation of cortisol; enhanced negative feedback to the HPA axis; and blunted HPA axis responsiveness. Furthermore, HPA axis changes seem clinically relevant, as they are associated with worse symptoms and/or disability and with poorer outcomes to standard treatments for CFS.

Regarding etiology, women with CFS are more likely to have reduced cortisol levels. Studies published in the past 8 years provide further support for a multifactorial model in which several factors interact to moderate HPA axis changes. In particular, low activity levels, depression and early-life stress appear to reduce cortisol levels, whereas the use of psychotropic medication can increase cortisol. Addressing these factors-for example, with cognitive behavioral therapy-can increase cortisol levels and is probably the first-line approach for correcting HPA axis dysfunction at present, as steroid replacement is not recommended.

Given what is now a fairly consistent pattern of findings for the type of HPA axis changes found in CFS, we recommend that future work focuses on improving our understanding of the cause and relevance of these observed changes.

Comment in: Neuroendocrine correlates of childhood trauma in CFS. [Nat Rev Endocrinol. 2012]

Source: Papadopoulos AS, Cleare AJ. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011 Sep 27;8(1):22-32. doi: 10.1038/nrendo.2011.153. https://www.ncbi.nlm.nih.gov/pubmed/21946893

Autonomic symptoms at baseline and following infectious mononucleosis in a prospective cohort of adolescents

Chronic fatigue syndrome (CFS) is a complex condition involving fatigue and musculoskeletal and cognitive symptoms. Six, 12, and 24 months following monospot-positive acute infectious mononucleosis (IM), 13%, 7%, and 4%, respectively, of adolescents met criteria for CFS.1 As part of their evaluation at baseline and 6, 12, and 24 months following IM, adolescents diagnosed with CFS and recovered controls completed questionnaires regarding autonomic symptoms.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896070/

Source: Katz BZ, Stewart JM, Shiraishi Y, Mears CJ, Taylor R. Autonomic symptoms at baseline and following infectious mononucleosis in a prospective cohort of adolescents. Arch Pediatr Adolesc Med. 2011 Aug;165(8):765-6. doi: 10.1001/archpediatrics.2011.124. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896070/ (Full article)

EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients–a case control study

Abstract:

BACKGROUND: Previous studies suggest central nervous system involvement in chronic fatigue syndrome (CFS), yet there are no established diagnostic criteria. CFS may be difficult to differentiate from clinical depression. The study’s objective was to determine if spectral coherence, a computational derivative of spectral analysis of the electroencephalogram (EEG), could distinguish patients with CFS from healthy control subjects and not erroneously classify depressed patients as having CFS.

METHODS: This is a study, conducted in an academic medical center electroencephalography laboratory, of 632 subjects: 390 healthy normal controls, 70 patients with carefully defined CFS, 24 with major depression, and 148 with general fatigue. Aside from fatigue, all patients were medically healthy by history and examination. EEGs were obtained and spectral coherences calculated after extensive artifact removal. Principal Components Analysis identified coherence factors and corresponding factor loading patterns. Discriminant analysis determined whether spectral coherence factors could reliably discriminate CFS patients from healthy control subjects without misclassifying depression as CFS.

RESULTS: Analysis of EEG coherence data from a large sample (n = 632) of patients and healthy controls identified 40 factors explaining 55.6% total variance. Factors showed highly significant group differentiation (p < .0004) identifying 89.5% of unmedicated female CFS patients and 92.4% of healthy female controls. Recursive jackknifing showed predictions were stable. A conservative 10-factor discriminant function model was subsequently applied, and also showed highly significant group discrimination (p < .001), accurately classifying 88.9% unmedicated males with CFS, and 82.4% unmedicated male healthy controls. No patient with depression was classified as having CFS. The model was less accurate (73.9%) in identifying CFS patients taking psychoactive medications. Factors involving the temporal lobes were of primary importance.

CONCLUSIONS: EEG spectral coherence analysis identified unmedicated patients with CFS and healthy control subjects without misclassifying depressed patients as CFS, providing evidence that CFS patients demonstrate brain physiology that is not observed in healthy normals or patients with major depression. Studies of new CFS patients and comparison groups are required to determine the possible clinical utility of this test. The results concur with other studies finding neurological abnormalities in CFS, and implicate temporal lobe involvement in CFS pathophysiology.

Source: Duffy FH, McAnulty GB, McCreary MC, Cuchural GJ, Komaroff AL. EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients–a case control study. BMC Neurol. 2011 Jul 1;11:82. doi: 10.1186/1471-2377-11-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146818/ (Full article)

Neuroimaging and the case of chronic fatigue syndrome

Abstract:

This article analyzes the use of neuroimaging in research into chronic fatigue syndrome. It reviews some works published in the 1990 s and investigates a specific aspect of these studies, namely the search for a cerebral abnormality, in the form of an altered activation pattern, which could provide a pattern for diagnosis and treatment of the disease. The understanding of chronic fatigue syndrome as a disease reduced to some cerebral findings is analyzed, arguing in favor of a broader vision of this disease that includes psychosocial elements of the patient’s life as opposed to entirely somatic explanations.

Source: Ortega F, Zorzanelli R. Neuroimaging and the case of chronic fatigue syndrome. Cien Saude Colet. 2011 Apr;16(4):2123-32. [Article in Portuguese]http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-81232011000400012&lng=en&nrm=iso&tlng=en (Full article)

A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis

Abstract:

To explore brain involvement in chronic fatigue syndrome (CFS), the statistical parametric mapping of brain MR images has been extended to voxel-based regressions against clinical scores.

Using SPM5 we performed voxel-based morphometry (VBM) and analysed T(1) – and T(2) -weighted spin-echo MR signal levels in 25 CFS subjects and 25 normal controls (NC). Clinical scores included CFS fatigue duration, a score based on the 10 most common CFS symptoms, the Bell score, the hospital anxiety and depression scale (HADS) anxiety and depression, and hemodynamic parameters from 24-h blood pressure monitoring. We also performed group × hemodynamic score interaction regressions to detect locations where MR regressions were opposite for CFS and NC, thereby indicating abnormality in the CFS group.

In the midbrain, white matter volume was observed to decrease with increasing fatigue duration. For T(1) -weighted MR and white matter volume, group × hemodynamic score interactions were detected in the brainstem [strongest in midbrain grey matter (GM)], deep prefrontal white matter (WM), the caudal basal pons and hypothalamus. A strong correlation in CFS between brainstem GM volume and pulse pressure suggested impaired cerebrovascular autoregulation.

It can be argued that at least some of these changes could arise from astrocyte dysfunction. These results are consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system (ANS).

Source: Barnden LR, Crouch B, Kwiatek R, Burnet R, Mernone A, Chryssidis S, Scroop G, Del Fante P. A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis. NMR Biomed. 2011 Dec;24(10):1302-12. doi: 10.1002/nbm.1692. Epub 2011 May 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369126/ (Full article)

Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome

Abstract:

Hypocortisolism is a frequent finding in individuals with chronic fatigue syndrome (CFS) with other research findings implying potential dysregulation of glucocorticoid signaling. Glucocorticoid signaling is under the influence of several pathways, several of which are of interest in the study of CFS. Oxidative stress and decreased antioxidant capacity are known to disrupt the hypothalamic-pituitary-adrenal (HPA) axis (Epel et al., 2004) and the presence of histone deacetylases (HDAC) could also impact glucocorticoid signaling.

The intent of this pilot study was to investigate the relationship among oxidative stress elements, select HDAC’s (2/3) and glucocorticoid receptor signaling in an elderly sample with CFS. Findings suggest increased histone deacetylase activity, lower total antioxidant power, in the context of decreased plasma cortisol and increased plasma dehydroepiandrosterone concomitant with decreased expression of the encoding gene for the glucocorticoid receptor. These findings support the presence of HPA axis dysregulation in elderly individuals with CFS.

Source: Jason L, Sorenson M, Sebally K, Alkazemi D, Lerch A, Porter N, Kubow S. Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome. Brain Behav Immun. 2011 Nov;25(8):1544-7. doi: 10.1016/j.bbi.2011.04.007. Epub 2011 Apr 28. https://www.ncbi.nlm.nih.gov/pubmed/21549189

The cerebralization of fatigue: an analysis of the cerebral hypothesis in the case of chronic fatigue syndrome

Abstract:

The article analyzes a number of conditions that allowed the brain to become established as an etiological hypothesis in the case of chronic fatigue syndrome (CFS), together with other hypotheses related to organic causes, such as viruses and immunity. It also addresses the process of cerebralization of personhood, which grew out of the use of neuroimaging for research and diagnostic purposes and according to which the brain constitutes the prime place for looking for the cause of the diseases – including CFS – within the context of a somatic culture, intensified at the end of the twentieth century.

Source: Ortega F, Zorzanelli R. The cerebralization of fatigue: an analysis of the cerebral hypothesis in the case of chronic fatigue syndrome. Hist Cienc Saude Manguinhos. 2010 Jun;17(2):289-305. [Article in Portuguese] http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-59702010000200002&lng=en&nrm=iso&tlng=en (Full article)