Primary headaches and their relationship with sleep

05/08/2013

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Yagihara F, Lucchesi LM‚ Smith AKA, Speciali JG 28
Sleep Sci. 2012;5(1):28-32
Primary headaches and their relationship with sleep
REVIEW ARTICLE
Cefaleias primárias e sua relação com o sono
Fabiana Yagihara1, Ligia Mendonça Lucchesi1, Anna Karla Alves Smith1, José Geraldo Speciali2
Study carried out at Departamento de Psicobiologia – Universidade Federal de São Paulo.
1 Departamento de Psicobiologia, Universidade Federal de São Paulo, Brasil.
2 Departamento de Neurociência e Ciências do Comportamento, Universidade de São Paulo, Campus Ribeirão Preto, Brasil.
Corresponding author: Ligia Mendonça Lucchesi. Departamento de Psicobiologia – Universidade Federal de São Paulo/UNIFESP. Rua Napoleão de Barros, 925 -
São Paulo (SP), Brazil - CEP 04024-002 - Phone: 55 (11) 21490155 - Fax: 55 (11) 55725092 - E-mail: ligia@psicobio.epm.br
Submitted: April 16, 2011; Accepted: September 05, 2011.
INTRODUCTION
A relationship between sleep and headaches has been reported
in lay and scientific literature for over a century.
Regulation of the sleep-wake cycle is mediated by the interaction
of different neural systems and their respective
neurotransmitters, components of which are shared with
ABSTRACT
There is a clear association between primary headaches and sleep
disorders, especially when these headaches occur at night or upon
waking. The primary headaches most commonly related to sleep
are: migraine, cluster headache, tension type, hypnic headache and
chronic paroxysmal hemicrania. The objective of this review was to
describe the relationship between these types of headaches and sleep
and to address sleep apnea headaches. There are various types of
demonstrated associations between sleep and headache disorders,
and the mechanisms underlying these associations are complex,
multi-factorial and poorly understood. Moreover, all sleep disorders
may be related to headaches to some degree; therefore, the evaluation
of patients with headaches should include a brief investigation
on sleep patterns and related complaints. Patients with headache at
night or upon waking who are resistent to the indicated treatment
require formal polysomnographic evaluation to exclude a treatable
sleep disorder.
Keywords: headaches, migraine disorders, obstructive, pain, sleep
apnea, sleep disorders.
RESUMO
Uma clara associação é observada entre cefaleias primárias e distúrbios
do sono, especialmente quando estas cefaleias ocorrem durante
a noite ou ao despertar. As cefaleias primárias mais relacionadas
ao sono são: migrânea ou enxaqueca, cefaleia em salvas, cefaléias
do tipo tensional, cefaléia hípnica e hemicrania paroxística crônica.
O objetivo desta revisão foi mostrar a associação estes tipos de
cefaleia e sono, abordando, também, a cefaleia da apneia do sono.
Existem associações demonstradas e de diversos tipos entre o sono
e transtornos de cefaleia e os mecanismos subjacentes a estas associações
são complexos, multifatoriais e ainda mal compreendidos.
Além do mais, todos os distúrbios de sono podem ter relação com
a cefaleia em maior ou menor grau e, por esta razão, a avaliação do
paciente com cefaleia deve incluir um breve questionamento sobre
o padrão ou queixas do sono deste. Pacientes com cefaleia noturna
ou ao despertar, refratários aos tratamentos indicados requerem
avaliação formal com polissonografia para exclusão de um distúrbio
do sono tratável.
Descritores: cefaleia, distúrbios do sono, dor, síndrome da apneia
obstrutiva do sono, transtornos de enxaqueca.
pain control systems. In general, pain affects sleep and vice
versa(1,2). We found that primary headaches with no clear
etiology by clinical and laboratory tests can be triggered by
either short or long periods of sleep, or by interrupted or
non-restorative sleep(3). Sleep is also effective in relieving
symptoms: 85% of individuals with migraine report that
they choose to sleep or rest because of a headache, and
many are forced to do it(4). Therefore, headaches and sleep
disturbances are common and often coexist in the same
individual(3,5), and this association is especially observed
when these headaches occur at night or upon waking(6,7).
Sleep-related headaches and the relationship between
sleep and headaches are not well understood, but
recent advances in the neurophysiology of sleep suggest
that the biological processes behind this association lie in
neuroanatomical systems common to both(5,6). Anatomical,
biochemical and physiological data support an inherent association
between normal sleep physiology and the genesis
of headaches in biologically predisposed individuals(3).
These data point to common pathophysiological aspects
of sleep, pain (headache) and mood, which involve the
hypothalamus, serotonin and melatonin(3). Preliminary
studies suggest that headaches tend to be associated with
rapid eye movement (REM) sleep and an increase in the
percentage of REM and slow wave sleep (SWS)(8).
Reviews of clinical and epidemiological studies
suggest a higher prevalence of sleep disorders in individuals
with certain types of headaches, such as migraine,
cluster headache and others(3,5,9). In addition, chronic daily
headache or headache on waking is strongly suggestive of
a sleep disorder. It is estimated that 4-6% of the general
population have a sleep disorder(10,11). Studies suggest that
of these individuals, approximately 18-60% are apneics
and 18% are insomniacs. Mitsikostas et al.(12) identified
obstructive sleep apnea syndrome (OSAS) in 29% of patients
with severe headaches resistent to standard treatments.
In a recent article, we examined the prevalence of
nocturnal awakening with headache (NAH) in a population
in Sao Paulo, Brazil. The prevalence of NAH (at least
once a week) was 8.4% in the population studied. The
Sleep Sci. 2012;5(1):28-32
29 Primary headaches and their relationship with sleep
identified risk factors for NAH were: female, age of 50-59
years, obesity, anxiety, restless leg syndrome (RLS), insomnia
and nightmares(13). However, no assessment was made
of headache type according to International Classification
of Headache Disorders, 2nd Edition (ICHD-II)(14).
The objective of this review is to discuss the main
types of primary headache most often associated with
sleep: migraine, cluster headache, tension type and hypnic
headache and chronic paroxysmal hemicrania (CPH). As
an exception to this proposal, we will discuss sleep apnea
headache, which is the only diagnosis of headache secondary
to a sleep disorder formally recognized by ICHD-II(14).
It is part of a subclassification of headaches related to hypoxia,
and one of its diagnostic criteria is that it can only
be confirmed after successful treatment of sleep apnea.
PRIMARY HEADACHES RELATED TO SLEEP
Migraine
Migraines are severe, usually unilateral headaches that
commonly present symptoms such as photophobia, phonophobia,
nausea, vomiting, mood disorders and sensory
abnormalities(15). They are closely related to sleep, and
migraines may occur during nocturnal sleep, after brief
periods of daytime sleep and upon waking. In fact, approximately
50% of migraine attacks occur between 4:00
a.m. and 9:00 a.m.(3). In addition, sleep problems are 3
times more frequent among patients who reported having
migraines(16). The migraine crisis can be triggered by lack
of sleep or sleeping too much; however, it often improves
or disappears after sleep(17). These crises are not associated
with a particular sleep stage: they may occur during
REM sleep or outside this period; they are more likely to
occur after long periods of SWS stage and/or upon waking
from REM sleep, when the patient is dreaming and
has a headache(3,18). The cyclical or periodic nature of the
attacks and their relationship with cycles (sleep, menstruation,
season of the year) and sunny days indicate circadian
mechanisms controlled by the hypothalamus(19).
Insomnia is among the sleep disorders most commonly
related to migraine and is present in one half to two
thirds of the migraine sufferers(16,17,20). The incidence of
parasomnias (sleepwalking, night terrors) is significantly
higher in patients with migraine than in the general population(
21). Sleepwalking may be considered a minor criterion
for the diagnosis of migraine(22). A higher migraine
frequency in narcoleptics has also been described(23). Recent
studies have identified a higher prevalence of RLS in
patients with migraine(24-26). In addition, because dopamine
is involved in the pathogenesis of both conditions, this
association could support the hypothetical dopaminergic
imbalance in RLS and migraine, as proposed by Cologno
et al. in 2008(27).
Cluster headache (CH)
Cluster headache pain is severe, excruciating (there are reports
of it being worse than labor pain or renal colic),
stabbing, puncturing, always unilateral and usually retroorbital(
28). It is associated with at least one of the following
signs on the ipsilateral side: conjunctival injection, lacrimation,
nasal congestion, rhinorrhea, forehead and facial
sweating, eyelid edema, miosis and ptosis.
Sleep has long been linked to CH. Initial observations
indicated that patients frequently or always report
CH onset during sleep, with pain so unbearable that it jolts
the person awake(29).
The attacks usually occur approximately ninety
minutes after the patient falls asleep, coincident with the
first episode of REM sleep. In fact, although data in the
literature are controversial, these attacks tend to occur
mostly during REM sleep(3). The pain may also begin in
stages 2 and 3 of NREM sleep, and patients may experience
a reduction of REM sleep and an increase of SWS
during cluster headaches(30). The frequency of cluster
headaches is one or two times per year, demonstrating
their circannual nature. Moreover, the influence of sleep
stages suggests hypothalamic involvement, in particular
the suprachiasmatic nucleus, in the common pathophysiological
processes of sleep and headache(19).
Cluster headache patients have a high risk for
OSAS, as reported in various studies(12,30,31); polysomnography
(PSG) is necessary in patients with cluster headaches
resistant to usual treatment(32-34).
A case study monitoring a patient with cluster headaches
over a 9-week actigraphy recording and repeated
PSG showed acute sleep-wake pattern changes and REM
sleep abnormalities, both of which diminished after the
episode(35). The authors concluded that in this patient, the
CH was associated with poor regulation of the sleep-wake
cycle, involving the biological clock and alertness mechanisms,
particularly in REM sleep; all of these abnormalities
were consistent with alteration of the posterior hypothalamus(
35). Studies using positron emission tomography
support this conclusion(36). Moreover, the efficacy of lithium
treatment has been shown to involve the hypothalamus,
resulting in selective accumulation and stabilization
of serotonin in the central nervous system, causing inhibition
of REM sleep and circadian rhythm changes(3).
Tension-type headaches
Tension-type headaches can be episodic or chronic. Diagnosis
of episodic cases requires a history of the last
10 headaches that lasted from 30 minutes up to 7 days,
and at least 2 of the following features: feelings of pressure/
squeezing; weak or moderate intensity; bilateral; not
aggravated by physical activity. Neurological and clinical
examinations must be normal(14). Nausea, vomiting, photo-
and phonophobia exclude a diagnosis of tension-type
headaches.
Chronic tension-type headaches occur more than
15 days per month (or more than 180 days per year) and
may have one (but no more) of the following features:
mild nausea, photo- and phonophobia(14).
Insomnia has been linked to chronic headaches and
may worsen the prognosis for tension-type headaches(31).
Hypersomnia, nocturnal bruxism and RLS are associated
with greater headache frequency, especially for tensiontype
headaches. Sleep fragmentation and/or increased
muscle activity during sleep is the likely mechanism in
Yagihara F, Lucchesi LM‚ Smith AKA, Speciali JG 30
Sleep Sci. 2012;5(1):28-32
these patients(37). Data supporting this hypothesis come
from PSG in patients with tension-type headaches that
showed frequent awakenings and reduced SWS(38).
Hypnic Headache
Hypnic headache is a rare type of primary chronic headache
occurring exclusively during sleep, usually in people
over 50 years of age, and its pathophysiology has not been
clearly established(39,40). It is characterized by mild to moderate
pain that wakes the patient. These headaches occur
more than 15 times per month and last 15-180 minutes(13).
It is the only type of headache that is strictly related
to sleep (both day and night) and wakes the patient.
Therefore, it is also called “alarm clock headache”(3,40).
Case reports suggest a relationship between waking and
headaches during slow-wave sleep(41,42), REM sleep or during
nocturnal desaturations(43). The relationship to REM
sleep may be false because headaches that wake the patient
during REM may have started in another stage(44). Studies
using laser-evoked pain potentials showed a late positive
component recorded in stages 2 and REM, and its amplitude
is significantly higher in trials followed by awakening(
45). In contrast, Bentley et al.(46) demonstrated that
higher thermal stimulus intensity is necessary to awaken
from slow-wave and REM sleep compared to stage 2.
However, when individuals are woken abruptly during the
REM sleep stage, the perception of pain is reduced by
sleep inertia, which does not occur when they are woken
in stage 2 or SWS(47).
Because hypnic headaches usually begin after the
fifth or sixth decade of life, their pathophysiology may
be associated with age-related changes in sleep patterns,
such as more frequent awakenings and a marked reduction
of SWS, as described for tension-type headaches(3). An association
with hypothalamic dysfunction is considered an
important pathophysiological mechanism for this type of
headache, because waking implies dysregulation of the
sleep/wake cycle(48). This type may also be related to reduced
melatonin, but it is important to note that melatonin
secretion is also reduced in other primary headaches
including migraine and cluster headache(49).
Chronic Paroxysmal Hemicrania (CPH)
CPH is a rare syndrome that usually manifests as a relatively
brief unilateral attack of severe pain, followed by
trigeminal-autonomic symptoms. These attacks occur
abruptly several times a day. The pain occurs mainly in the
ophthalmic trigeminal region, but other parts of the head
can be affected(14). There is no preferred time of day when
this type of pain begins, but when it occurs during sleep, it
is usually associated with REM. In this way, the attacks are
like cluster headaches, which are very similar, clinically(50).
SECONDARY HEADACHES RELATED TO
SLEEP: MORNING HEADACHES
In the ICHD-II, headache attributed to sleep apnea has
the code 10.1. within the group of headaches attributed to
homeostasis disorders(14). The diagnostic criteria include
recurring headaches that are present on awakening and
disappear after effective treatment of sleep apnea. Sleep
apnea headaches have the following features: occur more
than 15 days per month; pain or bilateral pressure not accompanied
by photophobia or phonophobia; resolved
within 30 minutes; confirmation of sleep apnea by allnight
PSG(14).
Some studies have reported a strong association
between morning headaches, OSAS(51,52) and snoring(52-54).
However, epidemiological studies have shown that this
type of headache is not specific to sleep-related breathing
disorders(55). In a study by Goder et al.(56), verification of
the PSG findings on the night preceding morning headaches
included a reduction in total sleep time, sleep efficiency
and the amount of REM sleep and an increased
number of awakenings. Complaints of morning headaches
are also reported at a rate 3-5 times higher among
patients who suffer from RLS(57).
RELATIONSHIP BETWEEN NOCTURNAL
AWAKENING WITH HEADACHE AND SLEEP
DISORDERS
There are few studies examining the relationship between
NAH and sleep disorders. Evans et al. (58) reported that
headaches that wake a person during the night are due to
interrupted sleep or one of the following underlying processes
that interrupt sleep: OSAS or nocturnal hypoxia/
hypercapnia, RLS or periodic movements during sleep,
psychophysiological insomnia and depression/anxiety. In
our epidemiological study of sleep disorders in São Paulo,
NAH was associated with insomnia, RLS, bruxism and
nightmares, but not with sleep apnea(13).
INVESTIGATION WITH PSG
A physician who examines a patient presenting with headaches
can take advantage of this auxiliary test. It is particularly
useful when confronted with nocturnal headache
or unusual awakening in the context of ICHD-II in the
absence of a psychosocial disorder or abuse of analgesics
and with a clinical history suggestive of sleep disorders(33).
PSG is also indicated in suspected cases of sleep-related
respiratory disorder, narcolepsy and parasomnias. Diagnosis
of insomnia is usually based solely on clinical history(29).
For well-defined primary headaches, it is possible
to waive a formal sleep study(29). As previously mentioned,
PSG may be necessary in patients with cluster headache
resistant to treatment(33).
CONCLUDING REMARKS
It is important to emphasize and consider possible neurobiological
associations between sleep and headaches. For
example, the hypothalamus is an important brain region
that facilitates sleep (anterior part) and maintains wakefulness
(posterior part). In addition to other hypothalamic
functions, such as homeostasis and pain control, its effects
on the transition from wakefulness to sleep or vice versa
may play a role in the mechanisms of headache(59).
Moreover, the association of symptoms of depression
and stress with many headache cases is explained in
part by actions of the serotonergic system, which is com-
Sleep Sci. 2012;5(1):28-32
31 Primary headaches and their relationship with sleep
mon to sleep, headache and pain and is located primarily
in the locus coeruleus and dorsal raphe nucleus(60).
In this brief review, we emphasized the following
aspects: - there are several demonstrated associations
between sleep and headache disorders; -the mechanisms
underlying these associations are complex, multi-factorial
and still poorly understood; - all major sleep disorders are
related to headache to some degree; - primary headache
disorders affect sleep or are directly related to sleep disorders
and performance throughout the day; - all assessments
of patients with headache should include questions
about sleep patterns and related complaints; - and patients
with headache at night or upon waking, who are resistant
to prescribed treatments, require formal PSG evaluation
to exclude a treatable sleep disorder.
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