Blackwell Science, LtdOxford,
UKCHACephalalgia0333-1024Blackwell Science, 2005264451456Original ArticlePrevalence of FMS in migraine patients G Ifergane et al.
doi:10.1111/j.1468-2982.2005.01060.x
Prevalence of fibromyalgia syndrome in migraine patients
G Ifergane1, D Buskila2, N Simiseshvely2, K Zeev3 & H Cohen3
1
Headache Clinic, Department of Neurology, 2Department of Medicine H and Rheumatic Disease Unit, Soroka Medical Centre, Ben-Gurion
University of the Negev, and 3Anxiety and Stress Research Unit, Ministry of Health Mental Health Centre, Faculty of Health Sciences, Ben-Gurion
University of the Negev, Beer Sheva, Israel
Ifergane G, Buskila D, Simiseshvely N, Zeev K & Cohen H. Prevalence of fibromyalgia syndrome in migraine patients. Cephalalgia 2006; 26:451–456. London.
ISSN 0333-1024
Fibromyalgia syndrome (FMS) is a chronic pain syndrome of unknown aetiology
characterized by diffuse pain over more than 3 months and tenderness in specific
sites named tender points. The aim of this study was to assess the prevalence and
severity of FMS among patients suffering from episodic migraine. Ninety-two
consecutive patients (20 male, 72 female) fulfilling the International Headache
Society criteria for migraine with and without aura from a tertiary headache clinic
were evaluated. A headache and generalized pain history was recorded, tender
points were evaluated by thumb palpation. The diagnosis of FMS was made based
on the 1990 American College of Rheumatology classification criteria for FMS.
Sixteen (22.2%) of the female patients and none of the male patients were diagnosed as suffering from FMS. Migraine severity and characteristics were similar
to other female migraine patients. Patients suffering from migraine–FMS had
lower quality of life scores and higher levels of mental distress. A high incidence
of FMS was found among female migraine patients but not in males. The coexistence of FMS should be considered when choosing a prophylactic migraine
therapy. 䊐 Central sensitization, fibromyalgia, mental distress, migraine, quality of life
Gal Ifergane MD, Department of Neurology, Soroka Medical Centre, PO Box 151, BeerSheva, Israel. Tel. + 97 2 8640 0660, fax + 97 2 8640 3660, e-mail galif@clalit.org.il
Received 6 June 2005, accepted 13 July 2005
Introduction
Fibromyalgia syndrome (FMS) is a chronic pain syndrome of unknown aetiology characterized by diffuse pain over more than 3 months and tenderness
in at least 11 tender points out of 18. Most FMS
patients (90%) are female and complain of pain,
insomnia, fatigue, and psychological distress (1).
Sleep disorders, chronic fatigue syndrome, irritable
bowl syndrome and mood disorders are common
comorbidities (2).
FMS patients show increased sensitivity to
mechanical, thermal and electrical stimuli, which
seems to suggest that abnormal central pain mechanisms may be important for the augmented pain
experience of FMS patients (3–5). Important central
nervous system mechanisms relevant to FMS pain
include temporal summation of pain (wind-up) and
central sensitization (6, 7).
© Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456
It has been suggested that central sensitization at
the level of the spinal dorsal horn/trigeminal
nucleus may also be involved in the progression of
migraine attacks, and due to prolonged nociceptive
inputs may result in supraspinal sensitization and
central neuroplastic changes that may be maintained, leading to conversion of episodic to chronic
headaches (8–10).
Cutaneous allodynia, pain or discomfort resulting
from a non-noxious stimulus to normal skin is a
common manifestation of this kind of sensitization
in migraine (11, 12). Usually it occurs in cephalic
areas, but in nearly half of the patients who experience allodynia, extracephalic allodynia exists as
well, suggesting the involvement of other nociceptive structures besides the trigeminal nucleus.
An increased incidence of FMS has been found
among patients with transformed migraine (13) and
it has been hypothesized (14) that episodic migraine,
451
452
G Ifergane et al.
chronic daily headache and FMS may actually be a
continuum of the same disorder.
The aim of this study was to assess the prevalence
and severity of FMS among patients suffering from
episodic migraine. In addition, we examined the
characteristics of patients with migraine and concomitant FMS.
Methods
Patients
We enrolled 92 consecutive patients fulfilling the
International Headache Society (IHS) (15) criteria
for migraine with and without aura treated in the
Headache Clinic of the Soroka University Medical
Centre in Beer-Sheva. The Headache Clinic is a
tertiary referral centre, and the patients were
referred by primary physicians as well as neurological and other specialty clinics. All participants
gave written informed consent after receiving a
detailed explanation of the purpose and design of
the study.
After signing an informed consent, the patients
were evaluated by one observer (N.S.). A headache
and generalized pain history was recorded. Manual
assessment of tenderness has been described in
great detail elsewhere (1). In all subjects, a count of
18 tender points at nine symmetrical sites was performed by thumb palpation. Definite tenderness at
any point was considered present if some involuntary verbal or facial expression of pain occurred or
withdrawal was observed. The diagnosis of FMS
was made based on the 1990 American College of
Rheumatology classification criteria for the diagnosis of FMS, namely: widespread pain for more than
3 months, on both sides of the body, above and
below the waist, and axial skeleton (cervical spine,
anterior chest, thoracic pain or low back) as
well as tenderness to palpation in 11 of 18 bilateral
sites (1).
The subjects were between the ages of 20 and
72 years, with a mean age of 42.5 ± 12.4 years.
Seventy-one (77.2%) of the sample population were
female. Two-thirds of them had suffered from
migraine for more than 10 years. Most of the patients
were married (76.1%), employed (72.8%) and their
mean level of education was 14.6 ± 3.4 years (range
3–26).
Patients suffering from current or recent substance
abuse disorders, psychotic symptoms or significant
cognitive impairment likely to interfere with study
procedures or with informed consent were excluded
from the study.
Study instruments
The questionnaires were filled out in the presence of
an interviewer and subjects were assisted in answering the questions, if needed. Each interviewer
ensured that all subjects clearly understood the content of each item and the different aspects of the
various component questions.
All
subjects
completed
the
following
questionnaires.
Demographics and background
Participants were asked to answer questions regarding their personal background (e.g. family status,
country of origin, level of education).
Headache Impact Test (HIT-6)
The HIT-6, a six-question survey, was used to measure the impact of headache on respondents’ lives.
The questions cover six aspects of functioning most
commonly impacted by headache: pain, role functioning (the ability to carry out usual activities),
social functioning, energy or fatigue, cognition, and
emotional distress (16). Scores are computed by
assigning a value of 6 to a response of ‘never’, 8 to
‘rarely’, 10 to ‘sometimes’, 11 to ‘very often’, and 13
to ‘always’; these values were used to recalibrate
scores from this static short form to scores from the
total HIT item pool and have them both in the same
norm-based metric (with a mean of 50 and a standard deviation of 10 in the general population of
recent headache sufferers). HIT-6 scores, derived by
adding the patient’s responses to all items, can range
from 36 (lowest possible score) to 78 (highest possible score). Scores of ≤ 49 reflect little or no impact;
scores between 50 and 55 reflect some headache
impact; scores between 56 and 59 reflect substantial
impact; and scores of ≥60 reflect severe headache
impact on the patient’s ability to function in everyday life (17).
Migraine Disability Assessment Scale
The Migraine Disability Assessment (MIDAS) scale
is used to quantify headache-related disability (18).
MIDAS is a brief and reliable headache-specific tool
which captures headache-related disability. Five
questions investigate the influence of headache on
everyday activities over the preceding 3 months.
Items 1 and 2 investigate paid work, enquiring as to
the number of days off work due to headache and
the number of days where productivity was reduced
by half or more. Items 3 and 4 ask the same questions
about household work. Item 5 enquires about
missed days of recreational, social and family
© Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456
Prevalence of FMS in migraine patients
activities. The total score is obtained by summing the
individual scores of the individual MIDAS items.
From the score, one of four disability grades is
assigned: grade I, minimal or infrequent disability
corresponds to a MIDAS score of 0–5; grade II, mild
or infrequent disability corresponds to a MIDAS
score of 6–10; grade III, moderate disability corresponds to a MIDAS score of 11–20; and grade IV,
severe disability correspondes to a MIDAS score
of ≥ 21.
Quality of life assessment
Quality of life (QoL) was assessed by SF-36 (19). This
is a health-related profile of QoL that contains 36
items and measures health status across three
domains: functional status, well-being and overall
evaluation of health. The Hebrew translation of the
SF-36 was validated in an adult general population
(20), and our group have used it on patients with
widespread pain, with and without FMS (21). The
SF-36 contains eight scales: physical functioning,
social functioning, and role limitations attributable
to physical and emotional problems, mental health,
vitality, bodily pain and general health. Each scale
generates a score from 0 to 100, with a high score
indicating better health and less body pain.
The Psychiatric Symptom Check List
This comprises 90 items measuring nine psychiatric
clinical subscales. The SCL-90 was developed as a
measure of general psychiatric symptom severity, as
a descriptive measure of psychopathology (22). The
clinical subscales are: somatization (12 items),
obsession-compulsion (10 items), interpersonal sensitivity (nine items), depression (13 items), anxiety
(10 items), hostility (six items), phobic anxiety (seven
items), paranoid ideation (six items) and psychoticism (10 items). The SCL-90 has been extensively
453
used and validated in Hebrew (23). Subjects are
required to rate specific complaints on a 5-point Likert scale running from 0 = ‘never’ to 4 = ‘frequently’.
Higher scores indicate greater distress. The Cronbach’s α values for the scales of somatization,
depression, anxiety and hostility in this study were
0.89, 0.90, 0.92, and 0.91, respectively.
Data analysis
Means, standard deviations and frequencies were
computed to summarize the distribution of values
for each variable. Age, years of education, family
status, number of years of marriage, immigrant/
veteran status in Israel (a country with high rates of
immigrations) and number of years in Israel were
analysed as continuous data and compared by oneway analysis of variance (ANOVA). The Sheffé post
hoc test was used to examine pair-wise differences
between the groups. χ2 tests were used for categorical data such as sex, place of birth and religion.
Results
Sixteen (17.4%) of the patients who met the IHS criteria for episodic migraine with and without aura
also met the currently accepted criteria of the
American College of Rheumatology for classification
of FMS. All of the patients who suffered from both
migraine and FMS were women (22.2% of the female
patients). Since none of the male patients suffered
from FMS, we compared migraine–FMS sufferers
with female migraine sufferers without FMS.
The demographic characteristics of the female
migraine patients with and without FMS are summarized in Table 1. The two groups, migraine
patients with and without FMS, did not differ significantly on any of the demographic measures, such as
Table 1 Characteristics of female migraine patients with and without fibromyalgia syndrome (FMS)
Variable
Age (years)
Mean ± SD, range
Employed, N (%)
Married, N (%)
Education (years)
Mean ± SD, range
Migraine duration, N (%)
≤10 years
>10 years
Migraine patients
with FMS
N = 16
Migraine patients
without FMS
N = 56
43.4 ± 11.4
20–60
10 (62.5%)
14 (87.5%)
14.4 ± 4
10–26
43.6 ± 12.5
21–72
46 (82%)
44 (78.5)
14.8 ± 2.8
9–21
4 (25%)
12 (75%)
18 (32.1%)
38 (67.9%)
© Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456
ANOVA
NS
NS
NS
NS
NS
NS
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G Ifergane et al.
Table 2 Headache characteristics among female Migraine patients with and without fibromyalgia syndrome (FMS)
Variable
Aura
Headache features
Unilateral
Throbbing
Moderate to severe intensity
Exacerbated by activity
Accompanying features
Vomiting/nausea
Phonophobia/photophobia
Exacerbating factors
Menstruation
Mental stress
Sleep deprivation
Nutritional
Migraine severity indices
HIT-6, mean ± SD (range)
MIDAS, mean ± SD (range)
Migraine patients
with FMS
N = 16
N (%)
Migraine patients
without FMS
N = 56
N (%)
ANOVA
1 (6.25%)
15 (26.7%)
NS*
14 (87.5%)
15 (93.7%)
15 (93.7%)
10 (62.5%)
48 (85.7%)
44 (78.6)
56 (100%)
36 (64.3%)
NS
NS
NS
NS
13 (81.2%)
14 (87.5%)
47 (84%)
51 (91%)
NS
NS
6 (37.5%)
11 (68.7%)
12 (75%)
8 (50%)
34 (60.7%)
38 (67.9%)
33 (59%)
23 (41%)
NS*
NS
NS
NS
49.2 ± 9.9 (30–64)
17.8 ± 23.4 (0–90)
48.4 ± 9.5 (30–66)
15.6 ± 21.1 (0–95)
NS
NS
*P = 0.08.
Table 3 Quality of life among Migraine patients with and without fibromyalgia syndrome (FMS) according to SF-36 scores
Variable
Migraine patients
with FMS
N = 16
Migraine patients
without FMS
N = 56
ANOVA
Physical function
Physical role function
General health perception
Emotional role
Social functioning
Bodily pain
Mental health
Vitality
Total
58.4 ± 17.1
39.1 ± 40.8
40.9 ± 22.4
68.75 ± 41.2
57.66 ± 13.1
38.37 ± 11.8
59.5 ± 18.7
35.3 ± 18.9
48.5 ± 11.5
85.4 ± 18.3
63.4 ± 40.16
70.1 ± 23.3
75.6 ± 39.4
50.4 ± 8.58
42.3 ± 11.36
67.8 ± 19.09
49.4 ± 18.76
63.04 ± 13.46
F(1,7) = 27.8, P < 0.00001
F(1,7) = 4.5, P < 0.04
F(1,7) = 19.9, P < 0.0003
NS
NS
NS
NS
F(1,7) = 6.9, P < 0.01
F(1,7) = 15.4, P < 0.0002
age, gender, marital status, level of education and
disease duration.
The features of the migraine attacks in patients
with and without FMS are summarized in Table 2.
Migraine with aura was less prevalent in female
migraine patients with FMS (6.25%) than in patients
without FMS (26.7%), but the difference was not
significant (P = 0.08). Migraine severity scores were
similar.
Migraine patients with FMS reported an
impaired quality of life in comparison with other
female migraine patients in almost all the domains
of the SF-36 (Table 3) and displayed higher levels
of mental distress (SCL-90 scores are displayed in
Table 4).
Distress symptoms, including hostility, interpersonal sensitivity, somatization, depression, anxiety,
phobia, obsession, paranoia and psychoticism, are
presented in Table 4. The subscales of somatization,
obsessive-compulsive, depression, phobic anxiety,
anxiety, anger-hostility, and psychoticism displayed
significant differences between the samples, with
significantly higher mean scores for migraine
patients with FMS compared with migraine patients
without FMS, representing higher levels of mental
distress.
© Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456
Prevalence of FMS in migraine patients
455
Table 4 Mental distress among migraine patients with and without fibromyalgia syndrome (FMS) according to Symptom Check
List (SCL)-90 scores
Variable
Migraine patients
with FMS
N = 16
Migraine patients
without FMS
N = 56
ANOVA
Somatization
Obsessive-compulsive
Interpersonal sensitivity
Depression
Hostility
Phobic anxiety
Anxiety
Paranoid ideation
Psychoticism
Global Severity Index
1.65 ± 0.81
1.1 ± 0.96
0.69 ± 0.61
0.98 ± 0.7
0.85 ± 0.84
0.49 ± 0.51
0.84 ± 0.55
0.31 ± 0.59
1.1 ± 0.9
0.9 ± 0.63
0.92 ± 0.69
0.53 ± 0.58
0.4 ± 0.56
0.49 ± 0.52
0.38 ± 0.59
0.13 ± 0.32
0.44 ± 0.58
0.14 ± 0.3
0.47 ± 0.56
0.45 ± 0.46
F(1,7) = 12.5, P < 0.0007
F(1,7) = 8.6, P < 0.005
NS
F(1,7) = 9.1, P < 0.004
F(1,7) = 6.3, P < 0.015
F(1,7) = 11.4, P < 0.0015
F(1,7) = 6.2, P < 0.015
NS
F(1,7) = 11.5, P < 0.0015
F(1,7) = 9.8, P < 0.003
Discussion
As many as 22.2% of the female migraine patients
also met criteria for FMS. Our results represent the
first comprehensive study using structured clinical
assessment measures of FMS in a group of migraine
patients. The prevalence of FMS among the migraine
patients in this study was significantly higher than
in the general population. The prevalence of FMS in
the general population (24, 25) in the USA has been
estimated to be between 2% and 3% (3.4% of women
and 0.5% of men). This finding further strengthens
previous observations of a high incidence of migraine among FMS patients (26).
The findings appear to indicate a clear association between FMS and migraine among women,
although whether this is one of causality or consequence is not clear. Since the study was conducted
in a tertiary headache clinic, this very high prevalence of FMS among migraine patients does not necessarily reflect the general population of migraine
sufferers. The study population suffered from more
severe migraines than reported in other groups of
patients, as reflected by high MIDAS scores. It thus
seems likely that a large proportion of female (but
not male) patients with severe migraine, who attend
headache clinics, suffer from FMS as well. Previous
reports (12) suggest that an even larger proportion
(35.6%) of patients with transformed migraine suffer
from the same condition. Community studies are
needed in order to establish comorbidity of these
conditions in the general population.
Migraine severity was similar in female migraine
patients with and without FMS. This does not necessarily apply to the general population of migraine
patients.
© Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456
Although not significant, almost all of the FMS–
migraine patients suffered from migraine without
aura. No other differences in headache features were
noted between the two groups.
FMS–migraine patients differed from other female
migraine patients in two major aspects. They
reported a much poorer quality of life and suffered
from higher levels of mental distress. It is not clear
whether the mental distress is caused by the FMS or
by the headache disorder, or is an independent exacerbating factor for either or both of them. The causative relationship between FMS and severe migraine
is not yet clear.
On the one hand, FMS may be an aggravating
factor for migraine, and on the other hand, the
migrainous sensitization of pain pathways may be
an aggravating or even a causative factor for the FMS.
It is also possible that the co-existence of both conditions is caused by a third, pain-sensitizing factor.
Whether FMS–migraine is a distinct syndrome
or not, the co-existence of both clearly affect the
patient’s well-being and should be taken into consideration when choosing therapeutic strategies.
Current evidence suggests efficacy of low-dose
antidepressants, cardiovascular exercises, cognitive
behavioral therapy (CBT), and patient education in
the treatment of FMS. Antidepressants and CBT are
also effective modalities in migraine management.
Comorbid disorders represent a major consideration in determining migraine therapy. The recognition of the association between migraine and FMS is
relevant for clinicians caring for migraine patients.
Diffuse aches and pain in migraine patients may
be attributed to concomitant FMS, and should be
considered in the choice of appropriate therapeutic
measures.
456
G Ifergane et al.
References
1 Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier
C, Goldenberg DL et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee.
Arthritis Rheum 1990; 33:160–72.
2 Mangweth B, Hudson JI, Pope HG, Hausmann A, De Col
C, Laird NM et al. Family study of affective spectrum
disorder. Arch Gen Psychiatry 2003; 60:170–7.
3 Granges G, Littlejohn G. Pressure pain threshold in painfree subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome.
Arthritis Rheum 1993; 36:642–6.
4 Staud R, Cannon RC, Mauderli AP, Robinson ME, Price
DD, Vierck CJ Jr. Temporal summation of pain from
mechanical stimulation of muscle tissue in normal controls
and subjects with fibromyalgia syndrome. Pain 2003;
102:87–95.
5 Graven-Nielsen T, Sorensen J, Henriksson KG, Bengtsson
M, Arendt-Nielsen L. Central hyperexcitability in fibromyalgia. J Musculoskel Pain 1999; 7:261–71.
6 Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD.
Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain 2001; 91:165–75.
7 Staud R, Price DD, Robinson ME, Mauderli AP, Vierck CJ.
Maintenance of windup of second pain requires less frequent stimulation in fibromyalgia patients compared to
normal controls. Pain 2004; 110:689–96.
8 Welch KM. Contemporary concepts of migraine pathogenesis. Neurology 2003; 61 (8 Suppl. 4):S2–8.
9 Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa
ZH. An association between migraine and cutaneous allodynia. Ann Neurol 2000; 47:614–24.
10 Kaube H, Katsarava Z, Przywara S, Drepper J, Ellrich J,
Diener HC. Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?
Neurology 2002; 58:1234–8.
11 Mathew NT, Kailasam J, Seifert T. Clinical recognition of
allodynia in migraine. Neurology 2004; 63:848–52.
12 Burstein R, Collins B, Jakubowski M. Defeating migraine
pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol 2004; 55:19–26.
13 Peres MFP, Young WB, Kaup AO, Zukerman E, Silberstein
SD. Fibromyalgia is common in patients with transformed
migraine. Neurology 2001; 57:1326–8.
14 Centonze V, Bassi A, Cassiano A, Munno I, Dalfino L,
Causarano V. Migraine, daily chronic headache and fibromyalgia in the same patient: an evolutive ‘continuum’ of
non organic chronic pain? About 100 clinical cases. Neurol
Sci 2004; 25:S291–S292.
15 Headache Classification Committee of the International Headache Society. The International Classification
of Headache Disorders. Cephalalgia 2004; 24 (Suppl. 1):1–
160.
16 Kosinski M, Bayliss MS, Bjorner JB, Ware JE Jr, Garber
WH, Batenhorst A et al. A six-item short-form survey for
measuring headache impact: the HIT-6. Qual Life Res
2003; 12:963–74.
17 Bayliss MS, Batenhorst AS. The HIT-6™: a user’s guide.
Lincoln, RI: QualityMetric 2002.
18 Stewart WF, Lipton RB, Kolodner K, Liberman J, Sawyer
J. Reliability of the migraine disability assessment score
in a population-based sample of headache sufferers.
Cephalalgia 1999; 19:107–14.
19 Stewart AL, Hays RD, Ware JE Jr. The MOS short-form
general health survey. Reliability and validity in a patient
population. Med Care 1988; 26:724–35.
20 Lewin-Epstein N, Sagiv-Schifter T, Shabtai EL, Shmueli A.
Validation of the 36-item short-form Health Survey
(Hebrew version) in the adult population of Israel. Med
Care 1998; 36:1361–70.
21 Neumann L, Berzak A, Buskila D. Measuring health status
in Israeli patients with fibromyalgia syndrome and widespread pain and healthy individuals: utility of the short
form 36-item health survey (SF-36). Semin Arthritis
Rheum 2000; 29:400–8.
22 Peveler RC, Fairburn CG. Measurement of neurotic symptoms by self-report questionnaire: validity of the SCL-90R.
Psychol Med 1990; 20:873–9.
23 Solomon Z, Mikulincer M, Bleich A. Characteristic expressions of combat-related posttraumatic stress disorder
among Israeli soldiers in the 1982 Lebanon War. Behav
Med 1988; 14:171–8.
24 Croft P, Rigby AS, Boswell R, Schollum J, Silman A. The
prevalence of chronic widespread pain in the general population. J Rheumatol 1993; 20:710–3.
25 Croft P, Schollum J, Silman A. Population study of tender
point counts and pain as evidence of fibromyalgia. BMJ
1994; 309:696–9.
26 Marcus DA, Bernstein C, Rudy TE. Fibromyalgia and
headache: an epidemiological study supporting migraine
as part of the fibromyalgia syndrome. Clin Rheumatol
[Epub ahead of print].
© Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456