and single-photon emissiontomography,
as well as disruption of thehypothalamic-pituitary-adrenal axis and sero-toninergic and noradrenergic pathways have beendemonstrated,
and a ‘distal dysautonomia’has been described in CFS patients.
As the fast response of the blood pressure (BP)and heart rate (HR) to acute stimuli is underautonomic nervous control, BP and HR measure-ments during orthostatic challenge can be used asone measure of cardiovascular autonomic activity.For this purpose, the head-up tilt test (HUTT) isused. Classical pathological reactions to the HUTTare: vasodepressor reaction, cardioinhibitory reac-tion, orthostatic hypotension and postural tachy-cardia syndrome. In studies using these outcomemeasures, evidence for abnormal cardiovascularreactivity was found in one half of CFS patients. Thelatter measures are non-specific, however, and alsooccur in a variety of disorders unrelated to CFS.
HR variability during the HUTT is another measureof cardiovascular reactivity in CFS.
As with theclassical outcomes of the HUTT, abnormalities of HR variability in CFS are not specific for thisdisorder.
A third method, recently proposed forthe study of the cardiovascular reactivity of CFSpatients involves computing BP and HR changesduring the course of a HUTT, followed by proces-sing the data by image analysis methods. These datareceive numerical expression as the ‘haemo-dynamic instability score’ (HIS). In our previousstudy,
the best cut-off differentiating CFS fromhealthy patients was HIS
0.98. HIS values above
0.98 were associated with CFS (sensitivity 97
). In a second study, we appliedthe proposed HIS threshold of
0.98 to studypopulations which served as ‘test groups’.
In the‘test groups’, similarly to the earlier ‘traininggroups’, the HIS threshold of
0.98 differentiatedbetween CFS patients (HIS
2.02, SD 4.07) andhealthy subjects (HIS
2.48, SD 4.07).
HISvalues higher than
0.98 were usually associatedwith CFS.
The diagnosis of CFS rests largely on patienthistory. In any illness defined by a group of symptoms, two questions arise: do the patients infact report the symptoms that investigators say theyshould, and do those symptoms distinguish patientswith CFS from other fatiguing illnesses?
Twostudies have validated the CFS questionnaires: thesymptoms of CFS, but not the control symptoms, aremuch more frequently reported by patients withCFS than by patients with other diseases whichproduce fatigue.
However, the differentiation of CFS from the other functional somatic syndromes,fibromyalgia and myofascial pain syndrome, maybe difficult, because features of these three dis-orders can overlap.
No physical finding or labor-atory test is generally accepted or in common use tostrengthen the diagnosis of CFS.
Two develop-ments might advance the diagnosis of CFS. The firstis based on a recent study showing that 72
of subjects in a group of patients with CFS hadincreased plasma levels of an abnormal 37 kDaprotein.
The possible application of this findingfor diagnostic purposes has not been appraised. Thesecond development is evaluation of dysautonomiaas a possible marker of CFS. A diagnostic role forthe HUTT classical endpoints, as well as for spectralanalysis of HR and BP variability in patients withCFS, has not been defined,
although wehave previously suggested that the HIS may beuseful in confirming the diagnosis of CFS.
Inthe present study, we reassessed the sensitivity of HIS
0.98 for the diagnosis of CFS in a newgroup of CFS patients. The reproducibility of the HISon repeated examinations was evaluated. Speci-ficity for the diagnosis of CFS was evaluated incomparison with controls, some exhibiting sharedclinical features with CFS (patients with non-CFSchronic fatigue, fibromyalgia, generalized anxietydisorder, neurally mediated syncope) and others notsuffering from fatigue (patients with FamilialMediterranean Fever, essential hypertension, healthysubjects).
All participants gave informed consent, and ourinstitution’s committee for human research app-roved the study. All patients were fully ambulatoryat the time of the study. The patients were not takingmedications for at least 2 weeks before the study.Technicians carrying out the HUTT were informedas to the patients’ diagnosis, but did not know of theintention to compare between the groups. Data of earlier studies, which used somewhat differentequations and were based upon slightly differentdependent measures
were revised, expandedand processed according to the latest equation.
40) were consecutive subjectsreferred from a CFS clinic for evaluation with theHUTT. All patients met the Centers of DiseaseControl and Prevention definition
of CFS, had noother diagnosable medical or psychiatric illness toexplain their symptoms, and did not have fibro-myalgia (FM), based on a specific tender pointscount
The subjects’ median age was 27