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circa de helft van de CVS-patiŽnten

voldoet aan strengere (ME-)criteria








Malterud en collega's hebben de diagnosecriteria voor ME, ME/CVS en CVS in kaart gebracht en

de studies naar het aantal ME- en/of CVS-patiŽnten op basis van drie situaties geÔnventariseerd.


Zij vonden 20 verschillende diagnosecriteria, waarvan ongeveer de helft serieus te nemen is.


De studies naar het aantal patiŽnten konden in drie groepen ingedeeld worden:

  • studies die diverse diagnosecriteria op dezelfde doelgroep toepasten (methode I: 5 studies),
  • studies die diagnosecriteria toepasten op een groep die vooraf op basis van andere diagnose-criteria (vaak Fukuda-criteria) geselecteerd werd: getrapte selectie (methode II: 12 studies), en
  • toepassing van ťťn type diagnosecriteria op verschillende doelgroepen (methode III: 21 studies).

Niet verrassend constateren de auteurs dat de Fukuda-criteria voor CVS het vaakst gebruikt zijn.


Het aantal patiŽnten dat aan bepaalde criteria voldoet, loopt in de diverse studies nogal uiteen.

Dit is het waarschijnlijk het gevolg van de manier waarop patiŽnten (vooraf) geselecteerd werden.


Zo constateerden Jason en Katz onlangs dat het logisch is dat je meer patiŽnten met psychische problemen zult aantreffen in een groep patiŽnten die naar de psycholoog verwezen werd (klik hier).


Duidelijk is wel dat de Holmes-criteria en de Canadese criteria strenger zijn dan de Fukuda-criteria.

Zo bleek uit een studie van Nacul en collega's uit 2011 dat ca. 0,19% van de mensen uit de huisartsen-data bases aan de Fukuda-criteria voldoet en 0,11% aan de strengere Canadese criteria voor ME/CVS.


Uit diverse studies blijkt ca. de helft van de CVS-patiŽnten aan strenge (ME-)criteria voldoet.

Het aantal mensen dat aan de Internationale Consensus-criteria voor ME voldoet, is (nog) onbekend.


Voor wat het de feiten aangaat, kan men de studie van Malterud en collega's waarderen.

Anders is het wat betreft de tegenstrijdige conclusies die de auteurs trekken uit hun onderzoek.


Aan de ene kant moeten volgens de auteurs subgroepen onderkend worden om het succes van behandeling (ze bedoelen uiteraard CGT/GET: zie de response op de kritiek van Marshall-Grasdinik)

te kunnen voorspellen, aan de andere kant hoeft er volgens hen weinig prioriteit geven worden

aan (de verfijning van) (nieuwe) diagnosecriteria, zoals de internationale consensus-criteria.


Het lijkt me toch dat (zie ingezonden reactie hieronder) dat het wel of niet aanwezig zijn van post-exertionele "malaise" het "succes" op activiteitenprogramma's (CGT/GET) aardig zal voorspellen...




Bron: vertaling van de internationale

concensus-criteria voor ME (klik hier)





Letter to the Editor



The essence of ME vs CFS: post-exertional "malaise" vs fatigue



Dear Editor,



With interest I have taken knowledge of the facts

presented by Brurberg and colleagues in BMJ Open 1

with regard to the case definitions and prevalences of

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS).



the conclusion to give low priority to

development and/or refinement of (new) case definitions of CFS (CFS/ME)

are incompatible with

the usefulness of classification of patients

according to symptom patterns to predict prognosis or effectiveness of therapies,

as also concluded by the authors.


It has been acknowledged that

the most frequently applied case definition for CFS 2

defines a heterogeneous patient population

with chronic fatigue as the principle symptom,

while neurological, immunological and other symptoms

are mandatory for the diagnosis ME according to (proposed) case definitions 3.


Above all, all ME (ME/CFS) case definitions require post-exertional malaise:

a long-lasting aggravation of distinctive symptoms after a minor exertion 3.


ME and CFS are by definition distinct clinical entities 4.


Based upon 1, 5 and other studies

it is estimated that 40-60% of patients fulfilling the criteria for CFS

suffer from post-exertional malaise and other symptoms, characteristic for ME 3.


Chronic fatigue is not obligatory in the ME case criteria,

implicating that ME patients do not have to meet the diagnostic criteria for CFS 4.


There is sufficient evidence that

a subdivision based upon the presence or absence of post-exertional malaise is essential,

e.g. to predict the outcomes of two therapies

proposed by the authors to be effective and safe for ME and CFS:

Cognitive Behavorial Therapy (CBT) and Graded Exercise Therapy (GET).


This subdivision,

which seem to be reflected by distinct (exercise-induced) immunological abnormalities 4,5,

is crucial,

because the (prolonged) negative physiological effects of exertion,

e.g. a substantial decrease of the workload and oxygen uptake

at exhaustion and at the anaerobic threshold at a second exercise test 24 hours later,

are likely to predict negative effects of (graded) exercise regimes,

like CBT and GET.


Post-exertional abnormalities in ME / CFS are essential,

irrespective of a 'specific hypothesised pathophysiology' 1.


The authors suggest that

CGT and GET are effective therapies for ME and CFS.


However, looking at the results of a large scale trial in the UK 6,

one must conclude that

the minimal improvement after CBT and GET in objective terms

is by far insufficient to qualify as clinical improvement of

CFS patients and the ME patient subgroup.


The authors blame

'patient groups and researchers

with vested interests in the belief that ME is a distinct somatic disease

seem unwilling to leave the position' 1.


A division between ME and CFS

has nothing to do with a dichotomy of an 'organic' (ME) versus 'psychic' (CFS) disorder,

since both ME and CFS seem to be accompanied by organic abnormalities.


The discussion is

not about whether psychosocial aspects should be taken into consideration,

but about the disproportionally great emphasis on these psychosocial aspects 7.


Lastly, the authors state that causal explanations for ME/CFS are limited.


However, there is sufficient evidence of

(reactivating) infections, distinct immunological abnormalities

(inflammation, immune activation, immunosuppression and immune dysfunction),

neurological aberrations, oxidative and nitrosative stress,

gastro-intestinal dysbiosis and inflammation, cardiovascular abnormalities and

circulatory deficits, mitochondrial dysfunction, decreased oxygen uptake/consumption,

HPA axis hypofunction (hypocortisolism and blunted response to provocation),

increased sensitivity of the (cellular) immune system and HPA axis to glucocorticoids,

and (long-lasting) deviant physiological responses to exertion

in CFS 2 patients or substantial subgroups thereof 3,7.


In conclusion,

the analysis conducted by Brurberg and colleagues

has yielded very useful insights.



the recommendation

to give low priority to development and/or refinement of (new) case definitions of CFS (CFS/ME)

are at odds with

the usefulness of classification of patients according to symptom patterns

(post-exertional malaise or not) to predict prognosis or effectiveness of therapies,

as stipulated by the authors, and

the observation that

"CFS" patients with post-exertional malaise

have distinctive abnormalities and react physiologically different to exertion,

when compared to "CFS" patient without post-exertional malaise,

which are likely to predict effects of exercise regimes, like CBT and GET.




Frank Twisk






  1. Brurberg KG, FÝnhus MS, Larun L, Flottorp S, Malterud K.
  2. Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME):

    a systematic review.

    BMJ Open 2014 Feb 7;4:2 e003973. doi: 10.1136/bmjopen-2013-003973.

    [FREE Full text]

  3. Fukuda K, Straus SE, Hickie I, et al.
  4. The chronic fatigue syndrome: a comprehensive approach to its definition and study.

    International Chronic Fatigue Syndrome Study Group.

    Ann Intern Med 1994;121:953-9. doi: 10.7326/0003-4819-121-12-199412150-00009.


  5. Carruthers BM, van de Sande MI, De Meirleir KL, et al.
  6. Myalgic encephalomyelitis: international consensus criteria.

    J Intern Med 2011;270:327-8. doi: 10.1111/j.1365-2796.2011.02428.x.

    [CrossRef] [Medline] [FREE Full text]

  7. Twisk FNM, Arnoldus RJ. T
  8. Comment and reply on: ME is a distinct diagnostic entity,

    not part of a chronic fatigue spectrum.

    Expert Opin Med Diagn. 2013 Jul;7(4):413-5. doi: 10.1517/17530059.2013.795147.


  9. Maes MM, Twisk FNM, Johnson C.
  10. Myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS),

    and chronic fatigue (CF) are distinguished accurately:

    results of supervised learning techniques applied on clinical and inflammatory data.

    Psychiatry Res 2012;200:754-60. doi: 10.1016/j.psychres.2012.03.031.


  11. White PD, Goldsmith KA, Johnson AL, et al.
  12. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy,

    and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.

    Lancet 2011;377:823-36. doi: 10.1016/S0140-6736(11)60096-2.

    [CrossRef] [FREE Full text]

  13. Maes M, Twisk FNM.
  14. Chronic fatigue syndrome:

    Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model

    based on inflammatory and oxidative and nitrosative stress pathways.

    BMC Med. 2010 Jun 15;8:35. doi: 10.1186/1741-7015-8-35.

    [FREE Full text]







Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review.

BMJ Open 2014 Feb 7;4:2 e003973 doi:10.1136/bmjopen-2013-003973.

Brurberg KG, FÝnhus MS, Larun L, Flottorp S, Malterud K.





To identify case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and

explore how the validity of case definitions can be evaluated in the absence of a reference standard.





Systematic review.










A literature search, updated as of November 2013, led to the identification of

20 case definitions and inclusion of 38 validation studies.



Primary and secondary outcome measure


Validation studies were assessed for risk of bias and

categorised according to three validation models:

  1. independent application of several case definitions on the same population,
  2. sequential application of different case definitions on
  3. patients diagnosed with CFS/ME with one set of diagnostic criteria or

  4. comparison of prevalence estimates
  5. from different case definitions applied on different populations.




A total of 38 studies contributed data of sufficient quality and consistency for evaluation of validity,

with CDC-1994/Fukuda as the most frequently applied case definition.


No study rigorously assessed the reproducibility or feasibility of case definitions.


Validation studies were small with methodological weaknesses and inconsistent results.


No empirical data indicated that

any case definition specifically identified patients with a neuroimmunological condition.





Classification of patients according to severity and symptom patterns,

aiming to predict prognosis or effectiveness of therapy, seems useful.


Development of further case definitions of CFS/ME should be given a low priority.


Consistency in research can be achieved

by applying diagnostic criteria that have been subjected to systematic evaluation.