University of Groningen
Fibromyalgia
Blécourt, Alida Cornelia Ebelina de
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1995
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Blécourt, A. C. E. D. (1995). Fibromyalgia: towards an integration of somatic and psychological aspects
Groningen: s.n.
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Chapter 4
In vivo 31P Magnetic Resonance Spectroscopy
(MRS) of tender points in patients with primary
fibromyalgia syndrome
A.C. DE BLÉCOURT, R.F. WOLF, M.H. VAN RIJSWIJK, R.L. KAMMAN,
A.A. KNIPPING, E.L. MOOYAART
Rheumatol Int 1991;11:51-54.
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Chapter 4
94
Chapter 4
Summary
31P Magnetic Resonance-Spectroscopy was performed at the site of tender points in
the trapezius muscle of patients with primary fibromyalgia syndrome. Earlier, in vitro
studies have reported changes in the high energy phosphate-metabolism in biopsies
taken from tender points of fibromyalgia patients.
The observed alterations could not be confirmed with in vivo Magnetic ResonanceSpectroscopy.
Introduction
Fibromyalgia syndrome is a commonly recognised form of non-articular rheumatism,
characterized by chronic musculoskeletal pain. A typical feature is the finding of so
called "tender points" on physical examination (1). Tender points are defined as areas
of prominent localized tenderness elicited on firm palpation of specific anatomic sites.
Fibromyalgia predominantly affects women in the age group from 20 to 50 years (1).
Criteria for the diagnosis of fibromyalgia according to Yunus are described in chapter
1. The American College of Rheumatology proposed new criteria for the
classification of fibromyalgia in 1990 (2). These criteria are 1) widespread pain in
combination with 2) tenderness at 11 or more of 18 specific tender points sites
(chapter 1).
The underlying mechanism of fibromyalgia is not clear. The possible etiologic role of
stress and other psychologic factors in fibromyalgia have recently been addressed
(3,4). Increasing attention has also been given to a possible organic origin of the
complaints (5,6). Histochemical as well as light and electron microscopic studies of
trapezius muscle biopsy samples of fibromyalgia patients have shown non-specific
abnormalities, and no evidence of inflammation (5). Significant histochemical
abnormalities are Type II fiber atrophy and moth-eaten appearance of Type I fibers.
Electron microscopy has revealed segmental muscle fiber necrosis with lipid and
glycogen deposition as well as subsarcolemnal mitochondrial accumulation. Papillary
projections of sarcolemnal membrane have also been described. The etiology of these
abnormalities is uncertain, but it is held possible that muscle spasm and ischemia may
contribute to the observed muscle changes (5).
Chemical analysis of biopsy samples from tender points in trapezius muscle has
shown an alteration in the content of high energy phosphates compared to biopsies
taken from identical regions in healthy volunteers (6). In particular, decreased levels
of adenosine tri- and diphosphate (ATP and ADP) and phosphocreatine (PCr) have
been reported, whereas levels of adenosine monophosphate (AMP) and creatine
appeared to be increased. From these results the authors have concluded that pain
experienced by fibromyalgia patients may be of muscular origin, and that muscle
hypoxia could play an important pathogenetic role in fibromyalgia.
95
Chapter 4
More evidence for the existence of abnormal oxygenation in fibromyalgia patients has
been provided by Lund et al. (7), using a multipoint oxygen electrode placed on the
muscle surface. They have reported abnormal or low muscle oxygenation at the site of
tender points in fibromyalgia patients.
In vivo 31P Magnetic Resonance Spectroscopy (MRS) provides the opportunity to
study high energy phosphate metabolism in muscle tissue (8-10). We used this noninvasive technique in order to detect metabolic differences between tender points in
fibromyalgia patients and identical regions in healthy volunteers.
Figure 1
TRANSVERSE SLICE OF THE UPPER THORACIC REGION, WITH THE VOLUME OF INTEREST (VOI) OF
THE RIGHT SHOULDER REGION, AT THE SITE OF THE TENDER POINT IN THE DESCENDEND
TRAPEZIUS MUSCLE (SEE THE WHITE AREA IN THE PICTURE)
96
Chapter 4
Patients and Methods
Ten patients diagnosed as having fibromyalgia according to the criteria of Yunus
(1981), were randomly chosen from the rheumatology outpatient clinic of the
University Hospital of Groningen (NL), see
table 1a . Informed consent was obtained
from all patients.
Six healthy volunteers served as a control group, see table 1a.
The patients were seen in the outpatient clinic for physical, laboratory and
radiological examination, followed by the 31P MRS.
The physical examination was performed by the same investigator (AB) and
comprised a functional assessment of the musculoskeletal system, including stature,
gait, mobility, global muscle strength (0-5), muscle tone, sensibility and myotendal
reflexes. Tender points as described by Smythe (11), were charted. We considered a
tender point positive when the patient complained of pain on palpation of the tender
spot or when the patient, on palpation, showed signs of pain such as flinching or
withdrawing. (In retrospect we were not able to see how many of our patients meet the
new American College of Rheumatology criteria for the fibromyalgia syndrome,
because we did not chart all the proposed 18 tender points.)
Laboratory investigation included ESR, haemoglobin level (Hb), leucocyte and
platelet count, differential blood cell count, electrolytes, AF, LDH, SGOT, SGPT,
Ca, P, triglycerides, cholesterol, CPK, thyroid hormone, serum protein
electrophoresis, glucose, ANA (Anti-Nuclear Antibodies) and rheumatoid factor, as a
screening for metabolic disorders or systemic autoimmune diseases. Urine was
checked for glucose and albumen.
X-ray images of shoulders and cervical spine were made, frontal and lateral view, in
search for possible anatomical causes of pain in the neck-shoulder region.
MR-Spectroscopy was performed on a 1.5 Tesla Philips whole body MR system with
a 31P resonance frequency of 25,855 MHz. Preceding spectroscopy a series of
transverse slices of the upper thoracic region was obtained by MR-imaging, thus
facilitating the positioning of the Volume Of Interest (VOI) in the appropriate region
(see figure 1 ).
Localization of the VOI, which is the area from which a spectrum is obtained, was
achieved using a modified ISIS technique (Image Selected In vivo Spectroscopy). The
31P spectra were acquired using a send/receive surface coil (diameter 15 cm) which
was positioned adjacent to the trapezius muscle at the site of the tender point. A
3
standard VOI was chosen of approximately 100 cm
from which 512 signal
accumulations were recorded with a repetition time of 3 s. Spectra were filtered and
deconvoluted using a standard set of parameters.
Because MR-Spectroscopy in this set up does not allow absolute measurement of the
concentration of the high energy phosphate metabolites, we used changes in peak area
ratios. This limitation arises from many operational and technical factors. At the
moment most measurements made from MR-spectra are ratios, where one peak is
97
Chapter 4
compared with another (12-14).
Peak area ratios Pi (inorganic phosphate)/PCr, PCr/
$-ATP and Pi/$-ATP were
calculated, using time domain fitting routines (12,13). The pH was calculated from the
relative distance of the Pi-peak to the PCr-peak on the PPM (parts per million)-scale
on the horizontal axis.
Results
On physical examination there were no structural disorders in stature or mobility, or
neurologic disorders. Laboratory and urine tests were normal, as well as the
radiological examinations.
All ten patients and the six healthy controls underwent 31P MR-Spectroscopy. The
spectra obtained for fibromyalgia patients and healthy controls looked similar initially
(figure 2a,b ).
Figure 2a
31P-SPECTRUM OF TRAPEZIUS MUSCLE TISSUE IN A HEALTHY VOLUNTEER
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Chapter 4
Figure 2b
31P-SPECTRUM OF TRAPEZIUS MUSCLE IN A FIBROMYALGIA PATIENT ON THE HORIZONTAL AXIS
THE PEAK POSITIONS ARE GIVEN IN PPM (PARTS PER MILLION) RELATIVE TO THE POSITION OF
THE PHOSPHOCREATINE PEAK
Calculations of peak area ratios Pi/
$-ATP, Pi/PCr and PCr/$-ATP, as well as the pH
were made (table 1b ). The ratios Pi/ßATP and Pi/PCr in the fibromyalgia patients
were not significantly higher than the ratios in healthy controls, in fact these ratios
were significantly lower (one tailed T-test p<0.05). There was no significant
difference in the PCr to ßATP ratio, as well as the pH between the patient and control
groups.
Table 1a
Patients
(n=10)
Controls
(n=6)
women/men
9:1
5:1
age (mean)
37-47 (41.8)
29-56 (43.2)
duration of complaints (years)
1-11 (5.7)
-
number tender points
3-13 (7.9)
-
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Chapter 4
Table 1b
Patients
Controls
Pi/$-ATP
0.29±0.11
0.39±0.09
Pi/PCr
0.14±0.03
0.21±0.02
PCr/$-ATP
2.01±0.68
2.07±0.23
pH
7.14±0.05
7.13±0.01
Discussion
MR-Spectroscopy provides a non-invasive method of studying in vivo energy
metabolism of intact muscle tissue.
It has been hypothesized by Bengtsson et al. that muscle tissue hypoxia may be of
pathogenetic significance in patients with fibromyalgia syndrome. Muscle hypoxia
will inevitably lead to alterations in the state of high energy phosphates, e.g.
decreased levels of PCr and ATP, and an increase in the level of Pi.
If a marked change in metabolism of energy-rich phosphates in fibromyalgic
muscle is present, 31P MR-Spectroscopy would be an appropriate method to detect
such an alteration. The results of our study did not show a decrease in PCr and ATP
or an increase in Pi in the trapezius muscle of the fibromyalgia group, compared
with the trapezius muscle of healthy controls. However these results are in contrast
with the findings of Bengtsson et al. We failed to show a significant decrease in
high energy phosphate metabolites in trapezius muscle of fibromyalgia patients.
The results of our study did not support the theory that a state of hypoxia causes
the muscle complaints in fibromyalgia, providing an organic origin for the illness.
Differences between our study and the study of Bengtsson et al. are that we did our
measurements in a in vivo environment; chemical analysis is performed in vitro.
We examined a greater volume of tissue (of the trapezius muscle) compared to the
amount needed for chemical analysis.
The spectroscopy was performed in a resting state. Further research in this field
should be done. As suggested by Kushmeric (15) a dynamic stress test may be
needed to reveal any changes in muscle metabolism in fibromyalgia patients,
because spectroscopy in a resting state might not be sufficient to reveal changes in
muscle metabolism in a fibromyalgia patient. It is possible that in a resting state
there is no alteration of metabolite content. However fibromyalgia patients in a
resting state often do complain of pain and feelings of fatigue in their muscles,
even when they have not performed any exercise beforehand.
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Chapter 4
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