CLINICAL FEATURES OF EPISODIC M IGRAINE
AND TRANSFORM ED M IGRAINE
A comparat ive st udy
José Carlos Bust o Galego
1, José Paulo Cipullo
2,
José Ant onio Cordeiro
3, Waldir Ant onio Tognola
2ABSTRACT - Transformed migraine (TM ) is one of t he most frequent t ypes of chronic daily headache. Eight y pat ient s: 40 w it h episodic migraine (EM ) and 40 w it h TM w it h ages ranging from 18 t o 60 years old w ere st udied. Females w ere t he majorit y. At first examinat ion, t he mean age w as similar in bot h groups. The init ial age of migraine at t acks w as significant ly smaller in t he TM group. Time hist ory of episodic at t acks w as similar in bot h groups. In t he EM group, t he headache w as predominant ly locat ed on only one side of t he head; w hereas in t he TM group, on more t han one side. There w as variat ion in t he charact er of pain and int ensit y in the TM group. Nocturnal aw akening w ith headache, aura and family history did not show significant association w ith EM or TM . The TM w as distinguished from the EM in relation to the frequency, location and pain intensity of the headache. Patients w ith early migraine headache onset may exhibit a further risk of developing TM .
KEY WORDS: t ransformed migraine, chronic daily headache.
Estudo comparativo entre as características clínicas da migrânea episódica e a migrânea transformada
RESUM O -A migrânea t ransformada (M T) é apont ada como a forma mais frequent e de cefaléia crônica diária. Foram est udados 80 pacient es: 40 com M E e 40 com M T ent re 18 e 60 anos de idade. As mulheres foram maioria. A idade média na primeira consulta foi semelhante nos 2 grupos. A idade de início das crises migranosas foi significant ement e menor no grupo M T. O t empo de hist ória de crises episódicas nos dois grupos foi semelhant e. No grupo M E predominou um só local da cefaléia enquant o no M T, mais de um. Houve variação no caráter e intensidade da dor na M T. Despertar noturno com cefaléia, aura e história familiar, não apresentaram associação significante com M E ou M T. A M T se distinguiu da M E quanto à frequência, localização e intensidade dolorosa da cef aléia. O início precoce das crises de m igrânea pode sugerir um f at or de risco para o desenvolviment o da M T.
PALAVRAS–CHAVE: migrânea t ransformada, cefaléia crônica diária.
The phenomenon of episodic migraine (EM ) trans-format ion int o chronic headache w as suggest ed by M at hew et al.1 in 1982. In t his st udy, t he aut hors
invest igat ed 80 pat ient s complaining of daily hea-dache. Out of t hose, 61 pat ient s (76.25%) have had migraine episodes in t heir past hist ory, before t he onset of daily headache. In 1987, M at hew et al.2.
used t he t erm of t ransformed migraine (TM ) t o des-cribe t his daily or almost daily headache w it h some clinical characteristics betw een migraine and tension-t ype headache, and w itension-t h a partension-t icular and natension-t ural hist ory. The pat ient s w it h TM usually experience mi-graine at t acks w it h or w it hout aura during adoles-cence or early adult life. The onset over t he years
has become more frequent . At t he same t ime, t hese pat ient s developed mild int erict al headaches, evol-ving to chronic daily headache (CDH)3. Several studies
reported that TM is the most common type of heada-ches, follow ed by chronic tension-type headache4-7.
In 1994, Silberst ein et al.8 proposed some crit eria
for TM diagnosis (Table 1).
The purpose of t his st udy w as t o compare clinical charact erist ics bet w een t he EM and t he TM .
M ETHOD
Eight y pat ient s, bot h sexes, t he ages ranging from 18 t o 60 years old w ere st udied. They w ere examined at t he headache out pat ient service of Hospit al de Base, M edical
Depart ament o de Ciências Neurológicas da Faculdade de M edicina de São José do Rio Pret o (FAM ERP), São José do Rio Pret o SP, Brasil:
1Professor Assist ent e M est re; 2Professor Adjunt o Dout or; 3Professor Adjunt o Livre Docent e.
Received 26 November 2001, received in final form 22 M ay 2002. Accept ed 6 June 2002
School of São José do Rio Pret o, SP. In t his clinical pros-pect ive st udy, t he pat ient s w ere consecut ively admit t ed and divided int o t w o groups. The first , 40 pat ient s w it h EM diagnosis, according t o t he Int ernat ional Headache Societ y ‘s crit eria9. The second, 40 pat ient s w it h TM
diag-nosis according t o Silberst ein et al.’s crit eria8. Pat ient s w it h
some chronic disease w ere not included in t he st udy. The st at ist ical analyses w ere performed by means of Analysis of Variance, St udent ’s t and Kruskal-Wallis’ t est s, and t he crossed frequencies t ables by means of Depen-dence Analysis10.
RESULTS
There w ere 33 f em ales (82.5%) and 7 m ales (17.5%) in t he EM group; 38 females (95%) and 2 males (5%) in t he TM group. At first examinat ion, t he mean age w as similar in bot h groups (p= 0.95) (Table 2). The mean durat ion of years of t he episodic at t acks w as also similar in bot h groups (p= 0.34) (Table 3), alt hough t he mean age at t he beginning of t he migraine at t acks w as significant ly low er in t he TM group (p= 0.022) (Table 4). In t he TM group, t he mean age at w hich t he t ransformat ion occurred t o CDH w as 34.8± 11.6 years and t he mean durat ion aft er t ransformat ion w as 2.24± 1.72 years. In t he EM group, 75% of t he pat ient s report ed hemicrania headache (37.5% alt ernant ing, 25% right -sided and 12.5% lef t -sided); 20% f ront al, 10% dif use, 5% occipt al and 5% in t he vert ex. In t he TM group, 80% report ed hemicrania headache (45% alt ernant ing, 20% right -sided and 15% left sided), 42.5 front al, 30% occipt al, 30% diffuse and 7.5% in t he vert ex. In t he EM group, headaches w ere predominant ly one-sided locat ion; w hereas in TM , on more t han one locat ion (p< 0.005).
All patients from the EM group complained of only pulsating pain; w hereas the patients from TM group, 57.5% pulsat ing pain, 40% pulsat ing and non-pulsating pain, and 2.5% non-non-pulsating pain. In the EM group, 72.5% of the patients described attacks of severe intensity, and 27.5% moderate. In the TM group,
62.5% described variat ion of int ensit y bet w een moderate and severe; 37,5% betw een mild and severe. This show ed that the variation of pain intensity w as more frequent in M T group (p< 0.0005).
The majority of patients in EM group (65%) repor-t ed arepor-t repor-t acks occurring forrepor-t nighrepor-t ly repor-t o monrepor-t hly, 15% w eekly, 12.5% w eekly to fortnightly, and 7.5% bimon-thly , quarterly and yearly. In the TM group, 80% of the patients reported daily occurrence of headaches and 20% almost daily (alw ays more than 15 days). In the EM group, 40% of the patients reported the hea-dache lasting from 1 to 3 days, 27.5% 1 day, 22.5% 1 to 2 days, 5% 5 days (attacks evolved into status migra-inosus)and 5% 4 to 8 hours. In this same group, 90% of the migraine attacks lasted up to 3 days (p< 0.0005). All pat ient s from t he TM group report ed hea-dache w it h a mean durat ion over four hours per day, according t o t he adopt ed crit eria. There w as a signi-ficant associat ion bet w een migraines and t he num-ber of associat ed sympt oms (p< 0.0005) (Fig 1).
In bot h m igraine t ypes, 2 or m ore sym pt om s occurred in t he majorit y of t he cases, alt hough in t he episodic, t he frequency of less t han t w o symp-t oms w as rare. The exissymp-t ence or non-exissymp-t ence of symp-t rig-gering fact ors (Fig 2) is relat ed t o t he migraine t ype (p= 0.006); more t han 85% of t he TM group presen-t ed a conpresen-t inuous headache inpresen-t ensified by presen-t rigger fac-t or (p= 0.049). In fac-t he EM group, 55% of fac-t he pafac-t ienfac-t s report ed t he w orsening of t he headache w it h head movement s (t o bend dow n and t o raise), 40% w it h physical act ivit y; 37.5% w it h coughing; 32.5% w it h odours and 17.5% w it h sneezing. Head movement s w ere report ed as a w orsening fact or by 52.5% of t he pat ient s in t he TM group, 40% report ed physical act ivit y; 12.5% odours; 10% coughing; and 5% sneezing. We found that no w orsening factor is greatly related w ith TM (p< 0.0005), according to the number of w orsening factors in the EM and TM groups.
In the EM group, 37.5% reported resting in a dark room as an improving factor; 30% resting; 22.5% the
Table 1. Proposed crit eria f or t ransf ormed migraine (Silberst ein et al.8).
A. Hist ory of episodic migraine meet ing any IHS crit eria 1.1 t o 1.6 B. Daily or almost daily (> 15 days/mont h) head pain for > 1 mont h C. Average headache durat ion of 4 hours/day (if unt reat ed)
D. Hist ory of increasing headache frequency w it h decreasing severit y of migrainous feat ures over at least 3 mont hs* E. At least one of t he follow ing:
1. There is no suggest ion of one of t he disorders list ed in groups 5 – 11 2. Such a disorder is suggest ed, but it is ruled out by appropriat e invest igat ions
3. Such disorder is present , but first migraine at t acks do not occur in close t emporal relat ion t o t he disorder
use of pain relievers, and 17.5% sleep. In the TM group, the use of pain relievers (dipyrone or associat ions w it h ergot amine) as an improving fact or w as report ed by 62.5% of our patients; 40% resting in a dark room; 20% rest ing; 5% sleep and 5% leisure act ivit ies. Fift y f ive percent of pat ient s f rom t he EM group and 62.5% from t he TM group report ed w aking up in t he morning or being w oken up very early in t he morning w it h headache.
To w ake up w ith headache w as not seen as a signi-ficant associat ion bet w een bot h groups (p= 0.12). Aura w as report ed by 20% of t he pat ient s from EM group; 33% in t he TM group. There w as no signi-ficant associat ion bet w een t he presence of aura and t he t ype of migraine (p= 0.133). Hist ory of headache similar t o migraine as occurring in first degree rela-t ives w as reporrela-t ed by 48% of rela-t he parela-t ienrela-t s from EM group, and 55% from t he TM group. There w as no
significant associat ion bet w een t he migraine t ype and family hist ory (p= 0.37).
DISCUSSION
EM and TM most commonly occur in women2,5-7,11-14.
Our resultssupport these findings; they also show ed that in the TM group, the w omen percentage (95%) w as higher than the one in EM group (82.5%).
We did not find significant difference in relat ion t o t he mean age at first examinat ion in bot h groups: EM (37.25± 10.32 years old) and TM (37.1± 11.71 years old). This may suggest t hat t he age is not a fact or relat ed w it h chronic migraine t ype. In our pa-t ienpa-t s, pa-t he mean durapa-t ion of EM before pa-t he pa-t rans-format ion w as 16.25± 12.26 years. Baldrat i et al.15
report ed a m ean durat ion of 19.3 years in EM ; M at hew et al.2 found 16± 11 years; Jevoux et al.7
9.6± 6.3 years and Sandrini et al.16 17.3± 1.9 years.
Fig. 1 Associat ed sympt ons t o pain episodes.
In our study, w e did not find significant difference w hen w e compared the mean duration in years of the episodic attacks betw een the EM group and TM group. There are few studies comparing the patients’ age at the beginning of EM , before the development to the chronic type w ith the initial age of migraine at-tacks in patients w ith episodic type. Baldrati et al.15
compared 50 patients w ith “ chronic migraine” and 90 patients w ith EM . They found the mean age of 19.5 years old at the beginning of EM in the patients w ith chronic migraine; however, it was not reported the initial mean age of the episodic attacks in the EM group.
The st udy of 489 pat ient s w it h TM by M at hew et al.2 show ed t he mean age of 22± 9.2 years old at
t he beginning of migraine at t acks. In 39 pat ient s, Jevoux et al.7 found t he mean age at t he beginning,
21.3± 8.7 years old. Sandrini et al.16 evaluat ed 90
pat ient s w it h CDH, out of t hem, 68 had an init ial hist ory of EM . In t hese pat ient s, t he mean age at t he beginning of t he episodic at t acks w as 19.4± 10.8 years old. In t he TM group, w e found init ial mean age of t he episodic at t acks 18.75± 10.6 years old. Comparing t he mean age at beginning of episodic at t acks in t he EM group (23.37± 10.0 years old) w it h
t he TM group (18.75± 10.16 years old), w e found an init ial age significant ly smaller in t he TM group. Considering t he t ime of evolut ion of t he episodic t ype of migraine w as similar in bot h groups as w ell as t he mean age of t he pat ient s at t he t ime of st udy, t his may suggest t hat an early beginning of migraine at t acks is a furt her risk fact or t o t he development of TM . In t he st udy of Solomon et al.4, pat ient s had
report ed t he beginning of headache in childhood an d ad o lescen ce, h o w ever t h er e is n o r ep o r t regarding init ial headache t ype.
M at hew et al.2 report ed a mean age of t
ransfor-m at ion t o CDH of 39± 11.2 years; Jevoux et al.7
31.1± 9.5 years. We found t his mean age t o CDH of 34.8± 11.6 years. M at hew et al.2 report ed a mean
durat ion aft er t ransformat ion t o CDH of 6± 5 years; Jevoux et al.7 3.96± 3.95 years. At first examinat ion,
w e found in t he TM group a mean durat ion aft er t ransformat ion t o CDH of 2.24± 1.72 years.
The locat ion m ainly unilat eral w as f ound by M at hew et al.2 in 58% of pat ient s in t he TM group,
and in 54% front al or front al t emporal. Jevoux et al.7 report ed t he unilat eral locat ion in 82% of t he
pat ient s, and in 61.5% front al, t emporal and front al-t emporal. The associaal-t ion beal-t w een more al-t han one locat ion w as report ed by 48.75 of t he pat ient s. Krym chant ow ski et al.13 f ound bilat eral f ront
al-t em p o r al l o caal-t i o n i n 2 2 .8 % o f al-t h e p aal-t i en al-t s; hemicrania non-alt ernat ing in 20.9%, bit emporal in 15.3%; diffuse pain in 12.1%; unilat eral alt ernat ing f r o n t al-t em p o r al h ead ach e in 8 .8 %; b if r o n t al headache in 8.4%; unilat eral per orbit al pain in 7.4%, and ot her locat ion in 26.5%. In our st udy, comparing t he locat ion of t he beginning of EM and TM w e f ound m ainly one locat ion in t he episodic t ype (unilat eral or front al or occipit al); in t he t ransformed, m ore t han one locat ion of t he beginning of t he headache (unilat eral, bilat eral, front al, occipit al and vert ex). Jevoux et al.7 found associat ion of pulsat ing
and non-pulsating pain in 66.7%; pulsating in 33.3%. Krymchant ow ski et al.13 report ed t hrobbing pain in
37.2% of the patients; pressing pain in 36.2%; 17.2% association of pressing and throbbing pain, and 7.4% ot her t ypes. Our result s show ed t his variat ion of pain charact er in TM group.
Jevoux et al.7 classified t he headache of TM as
severe in 10.3%; moderat e in 28.2%, and bet w een severe and mild, mainly mild, in 61.5%. Krymchan-t ow ski eKrymchan-t al.13 report ed all pat ient s w it h moderat e
daily headache, and in 40.5% int ermit t ent at t acks of pulsating pain aggravated by routine physical acti-vit ies, nausea and/or vomit ing, phot o and phonophobia. Our st udy show ed a great associat ion bet
-Table 2. Age in bot h groups at f irst examinat ion.
St at ist ic Episodic migraine Transformed migraine M ean (SD) 37.25 (10.32) 37.1 (11.71)
M edian 35.5 34
Range 18 – 55 19 – 59
SD, st andard deviat ion; values in years.
Table 3. Time hist ory of episodic at t acks.
St at ist ic Episodic migraine Transformed migraine M ean (SD) 13.88 (9.68) 16.25 (12.26)
M edian 10.5 12
Range 1 – 35 2 – 46
SD, st andard deviat ion; values in years.
Table 4. Age at beginning of t he migraine at t acks.
St at ist ic Episodic migraine Transformed migraine M ean (SD) 23.37 (10.0) 18.75 (10.16)
M edian 23.5 16
Range 7 – 45 7 – 48
w een t he migraine t ypes and t he pain int ensit y. The combined t ypes of t he int ensit y (severe, moderat e and mild) w ere more frequent in TM ; moderat e or severe in EM (p< 0.0005). Krymchant ow ski et al.13
reported their patients w ith daily moderate pain. Our pat ient s w it h TM present ed a frequency longer t han 15 days per mont h, and in 80%, t he headache w as daily. In t he episodic t ype, 65% of t he at t acks w ere fort night ly and mont hly.
M at hew et al.2 found 76% of pat ient s w it h
gas-t roingas-t esgas-t inal disorders such as nausea, vomigas-t ing and diarrhea; how ever, t hey did not point out t he percen-t age of percen-t hese symppercen-t oms; w hereas, visual dispercen-t urban-ces and “ neurological sympt oms” in 36% of t he pa-t ienpa-t s. Jevoux epa-t al.7 report ed phonophobia in 82%
of t he pat ient s; 77% phot ophobia; 51.2% nausea and 10.2% vomit ing.
We found a significant associat ion bet w een mi-graine and t he number of associat ed sympt oms. The frequency of less t han 2 associat ed sympt oms is rare in t he episodic migraine.
M at hew et al.2 found t riggering fact ors of
hea-dache in 88% of t he pat ient s; how ever, t hey w ere not dist inguished. Jevoux et al.7 ident ified t riggering
fact ors in 76.9% of t he pat ient s w it h TM . The most common w ere emotional disturbances in 64.1%; lack of sleep in 41%; fast ing in 30.7%, and sensit ivit y t o light and sm ell 48.7% and 51.2%, respect ively. Krymchant ow ski et al.13 report ed 76.2% of t he
pa-t ienpa-t s w ipa-t h pa-t riggering f acpa-t ors such as m enspa-t rual period, long fast ing, and st ress; how ever, t he per-cent age of frequency of t hese fact ors w as not dist in-guished. Our result s show ed t hat t he presence or absence of t riggering fact ors is relat ed w it h t he t ype of migraine; more t han 85% of t he pat ient s from t he TM had any t riggering fact or.
Jevoux et al.7 found w orsening factors in 92.3% of
the patients; mainly by physical activities reported by 76.9%, up and dow n head moving in 25.6%, lying dow n in 7.7%, sensibility to light, sound and odours in 7.7%. According to our results, no w orsening factor w as more common in the TM group. This may sug-gest t hat t hose pat ient s are more bearable t o t he w orsening factors reported by the patients of EM type. In t he series of pat ient s st udied by M at hew et al.2, Jevoux et al.7 and Krymchant w ski et al.13, t here
is not any improving fact or report ed in t he TM . Our result s show ed t hat in t he TM , t he use of pain-relieving medicat ions provided t o be t he main im-provement fact or (62.5%).This may suggest a high addict of t his medicat ion by t his group of pat ient s. M at hew et al.2 report ed 73.6% of pat ient s w it h
TM , w it h headache in t he f irst hours of t he day.
Jevoux et al.7 series of pat ient s, 69% w aking up early
in t he morning w it h headache. Krymchant ow ski et al.13 report ed 64.6% w it h some sleep sympt oms such
as: insomnia, int errupt ed sleep , noct urnal or aw a-kening headache, and ast henia.We did not find any significant associat ion of noct urnal or aw akening headache bet w een TM and EM groups.
M athew et al. reported 90.8% of the patients w ith migraine w ithout aura, and 9.2% w ith aura before the TM development. Krymchantow ski et al.13
descri-bed the initial diagnosis in 167 patients (77.7%) of migraine w ithout aura , and in 48 (22.3%) migraine w ith and w ithout aura, before the development to daily headache. Our results show ed that there is no significant association between aura and migraine type. Posit ive family hist ory of headache w as in 73.5% of TM cases st udied by M at hew et al.2 . Jevoux et
al.7 report ed in 64.1% of t he pat ient s. We did not
find significant associat ion of family hist ory in bot h t ypes of migraine.
CONCLUSION
The TM show ed some dist inguishedclinical cha-ract erist ics of t he episodic migraine t ype according t o t he frequency, locat ion and pain int ensit y of t he headache. Earlier beginning of migraine at t acks may be a furt her risk fact or for TM development .
Acknowledgements – We are grat eful t o Adília M . Pires Sciarra for t he help in t he English version.
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