Headache Medicine, v.1, n.1, p. 9-11, jan./fev./mar 2010 9

Chronobiological features in episodic and

chronic migraine

Aspectos cronobiológicos na enxaqueca episódica e crônica

ABSTRACTABSTRACT

ABSTRACT

Altered melatonin secretion and circadian, seasonal variations

have been shown in migraine patients, but little is known about

migraine chronobiological features. Two hundred migraine

patients were studied. Headaches were reported to occur after

changes in patients sleep schedule (46%), shift work (86%)

and traveling across time zones (79%). Patients significantly

delayed their sleep phase, 54% shifted their sleep phase.

Chronobiology is a relevant aspect in migraine patients.

ey words: ey words:

ey words: Melatonin; migraine; chronobiology.

RESUMORESUMO

RESUMO

Secreção alterada de melatonina e as variações sazonais têm

sido demonstrado em pacientes com enxaqueca, mas pouco

é sabido sobre as características cronobiológicas na enxa-

queca. Duzentos pacientes com enxaqueca foram estudados.

Dores de cabeça foram relatadas ocorrer após as alterações

do horário do sono em pacientes (46%), trabalho por turnos

trocados (86%) e viajar através dos fusos horários (79%).

Pacientes atrasaram significativamente a fase do sono, 54%

alteraram a fase de sono. Cronobiologia é um aspecto

relevante em pacientes com enxaqueca.

alavrasalavras

alavras

chave:chave:

chave: Melatonina; enxaqueca; cronobiologia.

ORIGINAL ARTICLE

Mario Fernando Prieto Peres

Andre Leite Gonçalves,

Marcelo Rodrigues Masruha,

Marlind Alan Stiles,

Charles Siow,

Stephen D Silberstein,

José Cipolla-Neto

Hospital Albert Einstein, FMABC, Unifesp, SP, Brazil;

Jefferson Headache Center, USA

Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo,SP, Brazil

Peres MFP, Gonçalves AL, Masruha MR, Stiles MA, Siow C, Silberstein SD, Cipolla-Neto J.

Chronobiological features in episodic and chronic migrainet. Headache Medicine. 2010;1(1):9-11

INTRODUCTION

The nervous system evolved to meet the demands of

environmental conditions, including the light-dark cycle,

in order to assure survival and reproduction of living

organisms. A synchronization system to adapt the internal

to the external environment is one of the key elements of

the central nervous system to maintain life. It has been

demonstrated in the past decades that the circadian

biological rhythm is not only the response to the 24-hour

day night environment but in fact is due to a system in the

brain.

Chronobiological disorders occurring in human being

can be divided in two types. 1) the environmental or

external variety, due to the life style and environment, as

in shift workers, individuals crossing time zones in the jet

lag syndrome, and in maladaptation to daylight savings.

2) the endogenous or internal type, including the delayed

and advanced sleep phase syndromes, and the non-24-

hour sleep -wake disorder with free-running circadian

rhythm.

It has been proposed the endogenous type may

underlie many conditions including depression, chronic

fatigue, fibromyalgia, and migraine.

Chronobiology is connected to headache disorders

in many ways, from experimental models

to clinical

settings and treatment.

Increasing evidence links melatonin

secretion and pineal function with cluster headache, hypnic

headache, hemicranias continua, migraine and its

10 Headache Medicine, v.1, n.1, p. 9-11, jan./fev./mar 2010

MARIO FERNANDO PRIETO PERES E COLABORADORES

comorbid conditions.

5-14

Pineal cysts have been found to

be linked with headache disorders.

Melatonin secretion has been studied in menstrual

migraine,

chronic migraine,

acute migraine,

migraine

status,

and migraine comorbid disorders.

All studies

found altered levels of melatonin in plasma or urine.

Clinical symptoms may fluctuate over time, in

menstrual migraine a cycle is evident, but headaches may

vary according to circadian and circannual variation.

Many migraine patients work in shift hours and travel

across time zones but it is unknown whether these could

be aggravating factors. Chronobiological features have

not been studied in detail.

We aimed in this study to evaluate clinical features of

chronic and episodic migraine patients regarding

chronobiological aspects.

PATIENTS AND METHODS

We included 200 consecutive migraine patients, men

or women, episodic or chronic migraine according to the

International Classification of Headache Disorders, 2nd

edition. Informed consents were obtained, the local ethics

committee approved the study. Patients filled out a

questionnaire about their headache and sleep features,

including chronobiological issues. Patients were asked if

headaches were aggravated when they changed their

sleep schedule, went to shift work or after traveling across

time zones. Time patients went to bed, time they slept,

and their preferred time to sleep were ascertained. A shift

of patients sleep cycle was then calculated subtracting the

time they really went to bed to the time they preferred go

to bed. Number of patients who delayed or advanced

their sleep phase (stayed up too late or went to bed too

soon) was calculated, based on more than 2 hours of

shift.

Chi square and Student t-test were applied for sleep

features comparisons between chronic versus episodic

migraine, with a p<0.05 considered statistically significant.

No missing data was observed in our sample.

RESULTS

Two hundred patients were studied, 162 (81%) women

and 38 (19%) men, 72 episodic migraine (36%), and

128 chronic migraine (64%) patients. Ninety-three patients

(46.5%) reported headaches after changing their sleep

schedule. Chronic migraineurs had more headaches after

changing sleep schedule than episodic migraine patients,

p < 0.05. Twenty-eight patients (14%) reported shift work.

86% of them reported having worse headaches after shift

work. Eighty six patients (43%) reported frequent traveling

across time zones, and 79% had worsening of headaches

when traveling. Patients significantly delayed their sleep

phase (22:46 h±01:20 h) vs. (22:22 h±01:17 h)

p<0.001, 108 patients (54%) shifted their sleep phase

ranging from -2:30 h to+05:00 h. Most of them – 75

(69%) delayed the sleep phase (stayed up too late), as

opposed to 33 (31%) that advanced it (went to bed too

soon). Patients shifting more than 02:00 h in both directions

represented 12.5% of migraineurs.

DISCUSSION

Chronobiological parameters have been studied in

several neurological disorders and have been implicated

in migraine mechanisms and treatment. Our data

suggest the presence of chronobiological dysfunction in

migraine patients. Our sample is from a tertiary

headache center, therefore a more severe patient

population. In the general population, with less severe

migraine individuals, chronobiological issues could be

less relevant, but, on the other hand, migraine patients

sensitive to time changes may not look for treatment. A

study on chronobiological features in the general

population would solve this question.

Migraine patients should be systematically asked

about their sleep patterns including other chronobiological

aspects, and should be managed accordingly. Severe

cases should avoid when possible travels across many

time zones, or take short term preventives, such as long

acting triptans or NSAIDs before the trip. Migraine patients

should avoid shift work when possible, or short term

prevention should also be considered.

More than 10% of patients shifted their cycle more

than 2 hours, most of them delayed their sleep phase.

Delayed sleep phase syndrome (DSPS) could be the cause

or consequence of migraine. The suprachiasmatic nuclei

and an altered melatonin secretion are probably behind

this clinical feature, but other neuropeptides may also be

involved including orexin, adiponectin, and others.

Melatonin supplementation is the first line choice for this

patients (migraine + DSPS).

Patients who shifted less than

2 hours may also benefit from melatonin supplementation.

Melatonin analogues such as ramelteon and agomelatin

should be tested.

Headache Medicine, v.1, n.1, p. 9-11, jan./fev./mar 2010 11

Since migraine with comorbid conditions, including

depression, anxiety, fatigue and fibromyalgia, have

decreased melatonin levels

7, 18

(i.e. a well known internal

synchronizer of the central and peripheral biological

clocks)19, chronobiological features may particularly be

implicated in those patients, a special attention to those

aspects is important in migraine patients.

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Endereço para correspondência

DrDr

. Mario F. Mario F

. Mario F

ernando Pernando P

ernando P

rieto Prieto P

rieto P

ereseres

eres

Al. Joaquim Eugenio de Lima, 881cj 708

São Paulo,SP, Brazil

http://cefaleias.com.br/

marioperes@cefaleias.com.br

CHRONOBIOLOGICAL FEATURES IN EPISODIC AND CHRONIC MIGRAINE