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Fysiske fund i ME

Fysiske Fund hos ME Patienter

Prof. Fluge og Mella finder fejl i stofkskiftet hos ME patienter, 2017. Her er de interviewt af Norsk TV.

11 Fysiske fund i ME

Oversigt over fysiske fund i ME-forskningen i de sidste 5 år

Distinct plasma immlune signatures in ME/CFS are present early in the course of illness, Horning, et al.

Brain abnormalities
“Brain-stem hypoperfusion was confirmed in all ME/CFS patients. Patients with ME/CFS have a generalized reduction of brain perfusion, with a particular pattern of hypoperfusion of the brainstem.” Brainstem perfusion is impaired in chronic fatigue syndrome, Costa DC, Tannock C, Brostoff J.

QJM.1995 Nov;88 11):767-73
http://www.ncbi.nlm.nih.gov/pubmed/8542261
“This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of SRTs (Simple Reaction Times) supports the notion of a deficit in motor preparatory areas of the brain.“

Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome,Davey NJPuri BK,Catley MMain JNowicky AVZaman R..Int J Clin Pract. 2003 May;57(4):262-4
http://www.ncbi.nlm.nih.gov/pubmed/12800454

We observed significant reductions in global gray matter volume…(which) was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.

Gray matter volume reduction in the chronic fatigue syndrome, de Lange, et al. Neuroimage. 2005 Jul 1;26(3):777-81.
http://www.ncbi.nlm.nih.gov/pubmed/15955487


Cardiac and circulatory problems
“The patients with severe CFS had significantly lower stroke volume and cardiac output than the controls.”

Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome,Peckerman A et al. Am J of the Med Sciences, 2003; 326(2):55-60
http://www.ncbi.nlm.nih.gov/pubmed/12920435

“A progressive cardiomyopathy caused by incomplete virus multiplication of EBV and/or HCMV in CFS patients is present.”

Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-Barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome, Lerner et al. In Vivo. 2004 Jul –Aug;18(4):417-24
https://www.ncbi.nlm.nih.gov/pubmed/15369178


Cognitive problems
“Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults.”

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: A BOLD fMRI study of verbal working memory, Lange G et al. Neuroimage 2005 June; 26(2):513-24
http://www.ncbi.nlm.nih.gov/pubmed/15907308


Exercise intolerance
Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Sanjay K. Shukla et al. 2015
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0145453#sec011

”CFS patients demonstrated significantly lower cardiovascular as well as ventilatory values at peak exercise, compared with the control group.

Physiological responses to incremental exercise in patients with cfs.Inbar O et al. Medicine and Science in Sports and Exercise2001 Sep; 33(9):1463-70
http://www.ncbi.nlm.nih.gov/pubmed/11528333

”Differences in ion transport and ion channel activity were evident at baseline and were exaggerated after exercise.”

Exercise responsive genes measured in peripheral blood of women with cfs and matched control subjects,Whistler T, Vernon SD et al. BMC Physiology. 2005 Mar 24;5(1):5
http://www.ncbi.nlm.nih.gov/pubmed/15790422

“The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. ” ”When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity”

Exercise capacity in chronic fatigue syndrome,De Becker P, De Meirleir K et al. Archives of Internal Medicine, 2000 Nov 27;160(21):3270-7
http://www.ncbi.nlm.nih.gov/pubmed/11088089

“The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress together with marked alterations of the muscle membrane excitability. These two objective signs of muscle dysfunction are sufficient to explain muscle pain and postexertional malaise.” 

CFS: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise,Jammes Y et al. Journal of Internal Medicine 2005, Mar; 257(3):299-310 http://www.ncbi.nlm.nih.gov/pubmed/15715687

Genetics
“Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Med. Outcomes Survey Short Form-36 scores, clinical phenotypes and severity.”

Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis,Kerr et al.J of Infect Diseases 2008 Apr 15;197(8):1171-1184  http://www.ncbi.nlm.nih.gov/pubmed/18462164

“Genomic studies showed that persistent cases express Epstein Barr virus-specific genes and demonstrate abnormalities of mitochondrial function.”

Chronic Fatigue Syndrome: Inflammation, Immune Function, and Neuroendocrine Interactions, Klimas NG and Koneru AO. Current Rheumatology Reports 2007 Vol. 9 (6)/Dec http://www.springerlink.com/content/1535x16058474m11/


Gut dysfunction
“Patients have a compromised gastrointestinal mucosal integrity which contributes to immune activation and is a major factor in CFS. The cause of intestinal barrier damage is multifactorial and complex. One factor is likely viruses (Epstein-Barr Virus and HHV-6).” ”A genetic predisposition to gastrointestinal problems likely exists” ME/CFS & Chronic Infection of the Gut – Notes on Dr. Kenny De Meirleir’s Presentation in Perth
http://www.prohealth.com/library/showarticle.cfm?id=8489&;t =CFIDS_FM

 “The results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in CFS and that it is a new target for drug development in CFS.” Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria,Maes and Leunis. Neuro Endocrinol. Lett. 29 December 2008,(6): 902–10.
http://www.ncbi.nlm.nih.gov/pubmed/19112401

Immune dysfunction
“Det ospecifika immunförsvaret i en undergrupp av ME/CFS-patienter är så
svagt att det ständigt får arbeta. Aktiviteten är dock för låg att det inte är mätbart i vanliga
prover.”
https://www.docdroid.net/xqMXUb8/me-gr-att-bota.rtf.html


“The presence of a 37 kDa 2-5A binding protein in extracts of peripheral blood mononuclear cells may distinguish patients with chronic fatigue syndrome from healthy subjects and those suffering from other diseases.” 

Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS),Snell, et al. In Vivo, 2005 Mar-Apr;19(2):387-90
http://www.ncbi.nlm.nih.gov/pubmed/15796202

“We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms”

Spinal fluid abnormalities in patients with chronic fatigue syndrome,Natelson BH et al. Clinical and Diagnostic Lab. Immunology, 2005 Jan;12(1):52-5
http://www.ncbi.nlm.nih.gov/pubmed/15642984


Mitochondrial dysfunction
”…a remarkable correlation is observed between the degree of mitochondrial dysfunction and the severity of illness.”

Chronic Fatigue Syndrome and mitochondrial dysfunction, Myhill,Booth and McLaren. Int J of Clinical and Experimental Med 2(1),1-16,2009
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2680051

”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”

Ventricular cerebrospinal fluid lactate is increased in cfs compared with generalized anxiety disorder: an in vivo 3.0 T 1H MRS imaging study, Sanjay J et al. NMR in Biomedicine, volume 22 Issue 3: 251 – 258, 2008
https://www.ncbi.nlm.nih.gov/pubmed/18942064


Orthostatic intolerance
“Symptoms of orthostatic intolerance, such as disabling fatigue, dizziness, diminished concentration, tremulousness, and nausea, are often found in patients with CFS.”

Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome,Hoad A, Newton. J et al.2008 QJM 2008 101(12):961-965 https://www.ncbi.nlm.nih.gov/pubmed/18805903


Oxidative Stress
“This review demonstrates that disorders in various IO&NS pathways provide explanations for the earlier mortality due to cardiovascular disorders in ME/CFS”,  Why ME/CFS may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS, Maes, Twisk. Neuro Endocrinol Lett. 2009;30(6):677-93.
https://www.ncbi.nlm.nih.gov/pubmed/20038921

 “We propose that the kindling and oxidative stress theories provide a heuristic template for better understanding the at times conflicting findings regarding the etiology and pathophysiology of this illness.” Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome  Jason, Porter, et. al,. J of Behavioral and Neuroscience Research 2009, Vo1. 7, 1-17, 2009
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022475/

Nitric oxide (NO) metabolites (nitrates) showed a much higher increase after a maximal physical test in CFS patients than in a group of matched subjects” .Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study, Suárez, García-Quintana. et.al.,J Womens Health (Larchmt). 2010 May,
http://www.ncbi.nlm.nih.gov/pubmed/20469961


Prognoses
“After 9 years QOL [quality of life] was the same as at diagnosis, only mental health had improved.”

Nine-Year Follow-Up of Danish Chronic Fatigue Syndrome: Impact on Health, Social, Vocational, and Personal Lives, Andersen, Permin and Albrecht. J of Chronic Fatigue Syndrome, 2008, vol. 14 (2):7-23
http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0802b&;L=co-cure&T=0&P=1694


Sleep
 abnormalities
“Higher levels of deep sleep and/or lower levels of light sleep have been reported in several all-night polysomnography studies in CFS patients.”

Paradoxical Nrems Distribution in ”Pure” Chronic Fatigue Patients. A Comparison With Sleep Apnea-Hypopnea Patients and Healthy Control Subjects,Le Bon O et al. Journal of Chronic Fatigue Syndrome, vol.14,(2 ) Jan. 2008, pp.45-59
http://www.informaworld.com/smpp/content~content=a902823230~db=all~jumptype=rss

“CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep.”

Sleep structure and sleepiness in chronic fatigue syndrome with or without co-existing fibromyalgia,Togo F et al. Arthritis Research & Therapy2008;10(3):R56.
http://www.ncbi.nlm.nih.gov/pubmed/18474105


Treatment
“Fifty-nine percent of the patients reported improved symptoms of CFS after long-term use of azithromycin. This confirms the results reported by De Becker et al.”
Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data, Vermeulen og Scholte, Journal of Translational Medicine 2006, 4:34doi:10.1186/1479-5876-4-34
http://link.springer.com/article/10.1186/1479-5876-4-34

“Sinus tachycardias decreased and abnormal cardiac wall motion improved. Serum antibody titers to EBV VCA IgM decreased. Patients resumed normal activities.”
Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up. Lerner, et al. In Vivo. 2007 Sep-Oct;21(5):707-13.
http://www.ncbi.nlm.nih.gov/sites/entrez


Viruses/Bacteria
“Studying peripheral blood mononuclear cells (PBMCs)from CFS patients, we identified DNA from a human gammaretrovirus,xenotropic murine leukemia virus–related virus (XMRV),in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthycontrols.”

Cronic fatigue syndrome is associated with chronic enterovirus infection of the stomach,
Chia and Chia. Journal of Clinical Pathology, 2008; 61:43-48.
http://jcp.bmj.com/cgi/content/abstract/61/1/43

“Parvovirus B19 may be involved in the pathogenesis of CFS.. The gastro-intestinal tract appears as an important reservoir of infection for several potentially pathogenic viruses.”
Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients, Frémont, Metzger, Rady, Hulstaert, De Meirleir. In Vivo. 2009 Mar-Apr;23(2):209-13
http://www.ncbi.nlm.nih.gov/pubmed/19414405

“The changes of immunological parameters in CFS patients with active dual infection were characterized by significant decrease of CD3+ and CD4+ T cells, significant increase of CD95+ cells and decrease of CD4+/CD8+ ratio.”
Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome,Chapenko et al.J Clin Virol. 2006 Dec;37 Suppl 1:S47-51
http://www.ncbi.nlm.nih.gov/pubmed/17276369

“The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.”
Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms, Nicolson, et al.APMIS. 2003 May;111(5):557-66.
http://www.ncbi.nlm.nih.gov/sites/entrez


Websites with ME/CFS research
ME research www.meresearch.org.uk/our-research/completed-studies/

Whittemore Peterson Institute http://www.wpinstitute.org/
CFS Research Foundation http://www.cfsrf.com/

Invest in ME http://www.investinme.org/index.html
Name Us http://www.name-us.org/index.html

HHV-6 Foundation: http://www.hhv-6foundation.org
The National CFIDS Foundation:  www.ncf-net.org

R.E.D. Laboratories http://www.redlabs.be/