The study of metabolism important for CFS research

Posted on 11/05/2014 by wames

Research abstract

Chronic fatigue syndrome (CFS) is a poorly understood condition that presents as long-term physical and mental fatigue with associated symptoms of pain and sensitivity across a broad range of systems in the body. The poor understanding of the disorder comes from the varying clinical diagnostic definitions as well as the broad array of body systems from which its symptoms present.

Studies on metabolism and CFS suggest irregularities in energy metabolism, amino acid metabolism, nucleotide metabolism, nitrogen metabolism, hormone metabolism, and oxidative stress metabolism.

The overwhelming body of evidence suggests an oxidative environment with the minimal utilization of mitochondria for efficient energy production. This is coupled with a reduced excretion of amino acids and nitrogen in general.

Metabolomics is a developing field that studies metabolism within a living system under varying conditions of stimuli. Through its development, there has been the optimisation of techniques to do large-scale hypothesis-generating untargeted studies as well as hypothesis-testing targeted studies. These techniques are introduced and show an important future direction for research into complex illnesses such as CFS.

Metabolism in chronic fatigue syndrome by CW Armstrong, NR McGregor, HL Butt, PR Gooley in Adv Clin Chem. 2014;66:121-72

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Transcranial magnetic stimulation potentially effective for chronic pain

Posted on 11/05/2014 by wames

Research abstract

Current data suggest that transcranial magnetic stimulation (TMS) has the potential to be an effective and complimentary treatment modality for patients with chronic neuropathic pain syndromes.

The success of TMS for pain relief depends on the parameters of the stimulation delivered, the location of neural target, and duration of treatment. TMS can be used to excite or inhibit underlying neural tissue that depends on long-term potentiation and long-term depression, respectively.

Long-term randomized controlled studies are warranted to establish the efficacy of repetitive TMS in patients with various chronic pain syndromes.

Transcranial Magnetic Stimulation for Chronic Pain, by NA Young, M Sharma, M Deogaonkar, in Neurosurg Clin N Am. 2014 Oct;25(4):819-832. Epub 2014 Aug 12.

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Increasing blood pressure with phenylephrine reduces OI symptoms

Posted on 11/04/2014 by wames

Research abstract

Chronic Fatigue Syndrome (CFS), with orthostatic intolerance is characterized by neurocognitive deficits, impaired working memory, concentration, and information processing.

In CFS, upright tilting (HUT) caused decreased cerebral blood flow velocity (CBFv) related to yperpnea/hypocapnia and impaired cerebral autoregulation; increasing orthostatic stress resulted in decreased neurocognition.

We loaded the baroreflex with phenylephrine to prevent hyperpnea, and performed N-Back, neurocognition testing in 11 controls and 15 CFS patients. HUT caused a significant increase in HR (109.4±3.9 vs. 77.2±1.6 bpm, p<0.05) and respiratory rate (20.9±vs. 14.2±1.2 bpm, p<0.05) and decrease in ETCO2 (42.8±vs. 33.9±1.1 Torr, p<0.05) in CFS vs. control. HUT caused CBFv to decrease 8.7% in controls, but fell 22.5% in CFS.

In CFS, phenylephrine prevented the HUT-induced hyperpnea/hypocapnia and the significant drop in CBFv with HUT (-8.1% vs. -22.5% untreated). There was no difference in control subject N-Back normalized response time (nRT) comparing supine to HUT (106.1±6.9 vs. 97.6±7.1 msec at n=4), and no difference comparing control to CFS while supine (97.1±7.1 vs 96.5±3.9 msec at n=4).

However, HUT of CFS subjects caused a significant increase in nRT (148.0±9.3 vs. 96.4±6.0 msec at n=4) compared to supine. Phenylephrine significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (114.6±7.1 vs 114.6±9.3 at n=4).

CONCLUSIONS:
Compared to control, CFS subjects are both more sensitive to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions. Increasing BP with phenylephrine can alter CBFv. In CFS subjects, mitigation of the HUT-induced CBFv decrease with phenylephrine has a beneficial effect on N-Back outcome.

Phenylephrine Alteration of Cerebral Blood Flow During Orthostasis; Effect on N-Back Performance in Chronic Fatigue Syndrome by M Medow et al in J Appl Physiol  2014 Oct 2. pii: jap.00527.2014. [Epub ahead of print]

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Pain and pressure pain thresholds in adolescents with CFS

Posted on 11/04/2014 by wames

Research abstract

Objectives: Although pain is a significant symptom in chronic fatigue syndrome (CFS), pain is poorly understood in adolescents with CFS. The aim of this study was to explore pain distribution and prevalence, pain intensity and its functional interference in everyday life, as well as pressure pain thresholds (PPT) in adolescents with CFS and compare this with a control group of healthy adolescents (HC).

Methods:  This is a case–control, cross-sectional study on pain including 120 adolescents with CFS and 39 HCs, aged 12–18 years. We measured pain frequency, pain severity and pain interference using self-reporting questionnaires. PPT was measured using pressure algometry. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.

Results: Adolescents with CFS had significantly lower PPTs compared with HCs (p<0.001). The Pain Severity Score and the Pain Interference Score were significantly higher in adolescents with CFS compared with HCs (p<0.001). Almost all adolescents with CFS experienced headache, abdominal pain and/or pain in muscles and joints. Moreover, in all sites, the pain intensity levels were significantly higher than in HCs (p<0.001).

Conclusions: We found a higher prevalence of severe pain among adolescents with CFS and lowered pain thresholds compared with HCs. The mechanisms, however, are still obscure. Large longitudinal population surveys are warranted measuring pain thresholds prior to the onset of CFS.

Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study, by Anette Winger et al in BMJ Open 2014;4:10.59200

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Vitamin D supplement doesn’t improve CFS/ME symptoms

Posted on 11/03/2014 by wames

Research abstract

Highlights

  • We randomised 50 patients with CFS/ME to receive six months of intermittent high-dose vitamin D or placebo.
  • Vitamin D did not improve pulse-wave velocity or flow-mediated dilatation of the brachial artery compared to placebo.
  • Vitamin D did not improve markers of oxidative stress or inflammation compared to placebo.
  • Vitamin D did not improve symptoms of fatigue compared to placebo.

Background and aims

Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome.

Methods and Results

Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months.

The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale.

50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22nmol/L at 6 months in the treatment group relative to placebo.

There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p=0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p=0.73).

Conclusion

High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome.

Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome – a randomised controlled trial  by M.D. Witham, F. Adams, S. McSwiggan, G. Kennedy, G. Kabir, J.J.F. Belch, F. Khan in Nutrition, Metabolism and Cardiovascular Diseases  Published Online: October 22, 2014

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Acupuncture and moxibustion treatment reduces chronic fatigue

Posted on 11/03/2014 by wames

Abstract
OBJECTIVE:
To observe the therapeutic effect of acupuncture and moxibustion interventions in the treatment of chronic fatigue syndrome (CFS).

METHODS:
A total of 133 CFS patients were randomized into acupuncture group (47 cases), warm-needling group (44 cases) and non-acupoint group (42 cases).

Manual acupuncture (MA) stimulation was applied to Baihui (GV 20), Danzhong (CV 17), Qihai (CV 6), Guanyuan (CV 4), bilateral Zusanli (ST 36), Hegu (LI 4), Taichong (LR 3) and Sanyinjiao (SP 6) for patients in the acupuncture group. For patients in the warm-needling group, moxa-heated needle was applied to Baihui (GV 20), Qihai (CV 6), Guanyuan (CV 4) and bilateral Zusanli (ST 36). Non-acupoints were located about 1-2 cm beside the Baihui (GV 20), Danzhong (CV 17), Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Taichong (LR 3), Sanyinjiao (SP 6) and Hegu (LI 4).

The treatment was given once daily for 20 days. The Chalder Fatigue Scale (14-item fatigue scale) was adopted to evaluate the changes of CFS before and after the treatment.

RESULTS:
In comparison with pre-treatment, the scores of Chalder Fatigue Scale including physical and mental fatigue and total score were significantly decreased in both acupuncture and warm-needling groups (P < 0.05, P < 0.01), but not in the non-acupoint group (P > 0.05) except physical score (P < 0.05).

The physical, mental and total scores of the acupuncture and warm-needling groups were significantly lower than those of the non-acupoint group (P < 0.05, P < 0.01), while the physical and total scores of the warm-needling group were markedly lower than those of the acupuncture group (P < 0.05).

After the treatment, the CFS patients’ satisfactory rates of the acupuncture, warm-needling and non-acupoint groups were 36.2% (17/47), 72.7% (32/44) and 35.7% (15/42), respectively.

CONCLUSION:
Both MA and warm-needling interventions have a good therapeutic effect in the treatment of CFS patients, while the latter is obviously better.

Randomized controlled clinical trials of acupuncture and moxibustion treatment of chronic fatigue syndrome patients, by C Lu, XJ Yang, J Hu, 2014 Aug;39(4):313-7 [Article in Chinese]

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PACE comment videos 2012-14

Posted on 11/03/2014 by wames

Results PACE Study -Movie

Results PACE Study -Movie part 2

Results PACE Study -Movie part 3

Results PACE Study -Movie part 4

5: Money and ME

6: ME Recovery Song

7: How’s That Recovery?

8: Science Friction in the UK

 

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Calls for use of immunotherapy to treat chronic pain

Posted on 10/30/2014 by wames

Cort Johnson writes:

We all know the medical profession is poor at providing pain relief in general, but its record with regards to neuropathic or nerve pain is something else indeed.

Despite the fairly large array of drugs physicians use (few of which were developed to reduce nerve pain), no more than 30-40% of  nerve pain patients receive as much as 50% relief from the medications doctors  provide. Despite research that has uncovered important factors in the production of pain, much clearly remains to be learned.

The production of pathological pain has been shown to be a very complex process. Researchers know, for instance, that damage to the ion channels on nerves, increased levels of excitatory neurotransmitters and reduced activity in the pain inhibition pathways in the brain all play a role.

These authors suggest, though, that a critical component of the pain production pathway – the immune system – has been, if not ignored, then not fully investigated.  Studies show that a variety of immune components, from mast cells to macrophages and cytokines to the microglia play a role in pain production.

Recent studies suggest that autoantibodies to the potassium channels – the dorsal root ganglia – key pain processing sites located just outside the spinal cord -are opening up new windows on how pathological pain may be produced. Other than corticosteroids and anti-inflammatories, however, few immune affecting drugs are used to fight pain.

Human immunoglobulin G (IgG) is an immune drug these authors believe may be useful in pain disorders where evidence of increased cytokine production can be found. IgG can be delivered intravenously (IVIg) or subcutaneously (SCIg) and may work by suppressing the immune system.

The fifteen members of this workshop came from Italy, Sweden, Switzerland, Japan, Canada, the U.K., and the U.S. to report on where and when IgG may be useful in treating chronic pain. Some studies were reported on and a good deal of the information derived from case studies.

Symposia Report:  Immunoglobulin G for the Treatment of Chronic Pain: Report of an Expert Workshop, by Stefano Tamburin et al in Pain Medicine 2014; 15: 1072–1082

Read more by Cort Johnson

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Severity scales in CFS/ME

Posted on 10/30/2014 by wames

Research abstract

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a physical and cognitive disabling illness, characterised by severe fatigue and a range of physiological symptoms that primarily affects women.

The immense variation in clinical presentation suggests differences in severity based on symptomology, physical and cognitive functional capacities.

In this review paper, we examined a number of severity scales used in assessing severity of patients with CFS/ME and the clinical aspects of CFS/ME severity subgroups. The use of severity scales may be important in CFS/ME as it permits the establishment of subgroups which may improve accuracy in both clinical and research settings.

Severity Scales for Use in Primary Health Care to Assess Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, by
SL Hardcastle, EW Brenu, S Johnston, D Staines, S Marshall-Gradisnik in Health Care Women Int. 2014 Oct 14:0. [Epub ahead of print]

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MRI shows white matter abnormalities in CFS brains

Posted on 10/30/2014 by wames

Stanford University radiology researchers have discovered that the brains of patients with CFS have diminished white matter and white matter abnormalities in the right hemisphere. Press release

Abstract

Purpose
To identify whether patients with chronic fatigue syndrome (CFS) have differences in gross brain structure, microscopic structure, or brain perfusion that may explain their symptoms.

Materials and Methods
Fifteen patients with CFS were identified by means of retrospective review with an institutional review board–approved waiver of consent and waiver of authorization. Fourteen age- and sex-matched control subjects provided informed consent in accordance with the institutional review board and HIPAA. All subjects underwent 3.0-T volumetric T1-weighted magnetic resonance (MR) imaging, with two diffusion-tensor imaging (DTI) acquisitions and arterial spin labeling (ASL). Open source software was used to segment supratentorial gray and white matter and cerebrospinal fluid to compare gray and white matter volumes and cortical thickness. DTI data were processed with automated fiber quantification, which was used to compare piecewise fractional anisotropy (FA) along 20 tracks. For the volumetric analysis, a regression was performed to account for differences in age, handedness, and total intracranial volume, and for the DTI, FA was compared piecewise along tracks by using an unpaired t test. The open source software segmentation was used to compare cerebral blood flow as measured with ASL.

Results
In the CFS population, FA was increased in the right arcuate fasciculus (P = .0015), and in right-handers, FA was also increased in the right inferior longitudinal fasciculus (ILF) (P = .0008). In patients with CFS, right anterior arcuate FA increased with disease severity (r = 0.649, P = .026). Bilateral white matter volumes were reduced in CFS (mean ± standard deviation, 467 581 mm3 ± 47 610 for patients vs 504 864 mm3 ± 68 126 for control subjects, P = .0026), and cortical thickness increased in both right arcuate end points, the middle temporal (T = 4.25) and precentral (T = 6.47) gyri, and one right ILF end point, the occipital lobe (T = 5.36). ASL showed no significant differences.

Conclusion
Bilateral white matter atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS.

Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome by Michael M. Zeineh, James Kang, Scott W. Atlas, Mira M. Raman, Allan L. Reiss, Jane L. Norris, PA, Ian Valencia, Jose G. Montoya in Radiology, Oct 2014

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