42 Headache Medicine, v.9, n.2, p.42-48, Apr./May/Jun. 2018

Thalyta Porto Fraga

, Paulo Samandar Jalali

, Paulo Sergio Faro Santos

, Alan Chester Feitosa de Jesus

Patologista, médica assistente do Departamento de Anatomia Patológica da Universidade Federal de Sergipe

Neurologista e neurofisiologista clínico, membro titular da Academia Brasileira de Neurologia

Neurologista, chefe do Setor de Cefaleia e Dor Orofacial, Departamento de Neurologia,

Instituto de Neurologia de Curitiba

Neurologista, membro efetivo da SBCe, membro titular da Academia Brasileira de Neurologia

Fraga TP, Jalali PS, Faro Santos PS, de Jesus ACF. Clinical and polysomnographic characteristics in

patients with morning headache. Headache Medicine. 2018;9(2):42-48

ORIGINAL ARTICLE

ABSTRACT

Background: The relation between headaches and sleep

disorders are complex and heavily questioned. However, there

is still controversy about this interrelationship. Objective: To

describe the clinical and polysomnographic characteristics of

patients with morning headache, and to compare them with

patients without morning headaches. Methods: Prospective

study between April and August 2009. One hundred and eight

patients were included consecutively and by convenience. All

patients were submitted to polysomnography and were

distributed in the group with headache (group 1) or the group

without headache (group 2). Results: Morning headache was

reported by 33 (30.6%) patients, 17 (51.5%, p = 0.02) women.

The clinical characteristics in the group of morning headache

were 42.4% with disease in upper respiratory system, 72.7%

with anxiety, 45% with headache in general, 54% with

neurocognitive symptoms, 81.2% reported non restorative sleep

and 60.6% had insomnia (all p< 0.05). Among the

polysomnographic features surveyed, the only variable that

showed statistical significance was wake after sleep onset.

Almost 43% (vs. 20%) of patients with morning headaches were

in normal range. Conclusions: It was not possible to conclude

that the presence of the increase apnea/hypopnea indices,

desaturation relevant and intermittent and disruption of sleep

patterns are sufficient to modulate, by itself, the occurrence of

morning headaches. Sleep disorders can act as a trigger for

morning headaches in susceptible individuals with specific

clinical profile

Keywords: Polysomnography, headache, sleep disorders

RESUMO

Introdução: As relações entre cefaleia e distúrbios do sono

são complexas e muito questionadas. No entanto, ainda exis-

te muita controvérsia a respeito dessa inter-relação. Objeti-

vo: Descrever as características clínicas e polissonográficas

apresentadas por pacientes com queixa de cefaleia matinal,

comparando-as com os resultados dos pacientes sem cefaleia

matinal. Métodos: Estudo prospectivo realizado entre abril

e agosto de 2009. Foram inclusos 108 pacientes com enca-

minhamento para realizarem polissonografia, de modo con-

secutivo e por conveniência. Os pacientes eram distribuídos

no grupo com cefaleia (grupo 1) ou no grupo sem cefaleia

(grupo 2). Resultados: Cefaleia matinal foi relatada por 33

(30,6%) pacientes, sendo 17 mulheres (51,5%; p=0,02). As

características clínicas do grupo com cefaleia matinal foram:

42,4% com doenças em vias aéreas superiores, 72,7% com

ansiedade, 45% com queixa de cefaleia em geral, 54% com

queixas neurocognitivas, 81,2% relatavam sono não repara-

dor e 60,6% tinham insônia (todas com p<0,05). Entre as

características polissonográficas pesquisadas, a única variá-

vel que mostrou significância estatística foi tempo acordado

após início do sono. Quase 43% (vs 20%) dos pacientes com

cefaleia matinal estavam na faixa de normalidade. Conclu-

são: Não foi possível concluir que a elevação do índice de

apneia/hipopneia do sono, dessaturações relevantes intermi-

tentes e a desorganização da arquitetura do sono sejam sufi-

cientes para modular, de forma isolada, a ocorrência da

cefaleia matinal. Os distúrbios do sono podem funcionar como

um gatilho para a cefaleia matinal em indivíduos predispos-

tos que se apresentam com determinado perfil clínico.

Palavras-chave: Polissonografia; Cefaleia; Distúrbios do sono

Clinical and polysomnographic characteristics in patients

with morning headache

Características clínicas e polissonográficas em pacientes com queixa de cefaleia matinal

Headache Medicine, v.9, n.2, p.42-48, Apr./May/Jun. 2018 43

INTRODUCTION

Headaches and sleep disorders are much studied

morbidities high prevalence in the general population

(1-4)

and

which entail great damage to the quality of life of patients.

(5-7)

The relationship between sleep and headaches is

complex, multifaceted and is questioned about the

intercausality between both.

(1-4)

In an attempt to facilitate

the determination of the relationship between headaches

and sleep disorders, ratings were created.

(1,8)

Among them,

the classification of Paia and Hering,

(1)

which determines

the following points: a) sleep disorders causing headache;

b) headache causing sleep disturbances and c) headaches

and sleep disorders triggered by secondary diseases.

Physiopathological indications for the relationship

between headache and sleep indicate that the neuroanatomic

base for both disorders may be in the brainstem.

Periarqueductal gray matter (PAG) and nucleus raphe

magnus (NRM) lesions may induce symptoms of migraine.

(9)

In addition, regional blood flow studies show that regions of

the brainstem that match the area of neurotransmission and

NRM noradrenergic locus ceruleus (LC) are activated during

acute attacks of migraine.

(10)

Cells in this region play a crucial

role in REM sleep (Rapid Eye Movement)

(11)

and it is believed

that a disturbance in the regulation of the cells can form the

basis of narcolepsy/catalepsy.

(9)

Recently, functional imaging

data reinforced the crucial role of the hypothalamus in

trigemino-autonomic headache,

(12)

not forgetting the role of

the hypothalamus in sleep-vigil cycle.

(13)

Until the second edition of the International Classification

of Headache,

(14)

in 2004, the morning headache was not

considered a nosological entity. But in the third edition it was

included

(15)

as sleep apnea headache (ICHD-3b 10.1.4) in

the topic 'Headache attributed to disruption of homeostasis'.

It is known that the headache upon awakening can be part

of the clinical picture of patients with obstructive sleep apnea

syndrome

(14)

(OSA), as well as other respiratory disorders,

and headache (primary or secondary).

(15,16)

Thus, one can see that there is a relationship between

headaches and sleep disorders. However, in spite of the

contributions given by ratings and studies, the only consensus

among the various authors is that this relationship is not

clear and further studies are needed for better clarification.

MATERIAL AND METHOD

Patients

Between April and August of 2009 were included 108

patients in consecutive mode and by convenience. All patients

had to undergo polysomnography (PSG). Patients were

oriented on researching and all who agreed to participate

signed an informed consent, in accordance with the standards

of the Declaration of Helsinki. After that, they filled a

questionnaire of pre-polysomnography, in which the presence

or absence of morning headache allocated them in distinct

groups. They were distributed in Group 1 (with morning

headache) or Group 2 (no morning headache). In addition

to the analysis of questionnaire data were also considered

the polysomnography. Patients younger than 18 years were

excluded from the sample. The study was approved by the

ethics and Research Committee of the Federal University of

Sergipe, process # 0097.0.107.000-09.

Polysomnographic assessment

Polysomnographic assessment was made using the Brain

Net System 36 of EMSA. The following variables were

monitored: 4 EEG (C3/C4/A2-A1-A2-O1/O2/A1)

according to the international system,

(10-20)

eletrooculography

to the right and left, submentonian electromyogram and

electrocardiography. The air flow was monitored by a

pressure nasal cannula and a thermistor. Respiratory

movements were assessed by thoracic and abdominal straps.

Snoring has been evaluated by a microphone around the

neck and oxygen saturation during sleep was continuously

measured using a pulse oximeter.

Leg movements were recorded with electromyography

on the right and the left tibia. PSG data were evaluated

according to the criteria of Rechtschaffen & Kales and the

new criteria of the American Academy of Sleep Medicine

(AASM, 2007). Sleep-disordered breathing was diagnosed

following the criteria of the AASM Sleep Scoring Manual

for 2007.

Apnea is defined as ≥90% the reduction of the amplitude

of the air flow for 10 seconds detected by thermistor. Hypopnea

is a reduction in the amplitude of a valid measurement of

breath ≥30% of the normal and associated with oxygen

desaturation ≥4%. Obstructive sleep apnea and hypopneaare

typically distinguished of the central event by detection of

inspiratory efforts during the event. The apnea-hypopnea index

(AHI) was calculated by the number of apneas and hypopneas

per hour of sleep. Sleep apnea syndrome was determined

using the criteria: AHI <5, AHI 5 - <15, AHI 15 - <30

and AHI >30. The patients were classified with mild OSA

(AHI 5 - <15), moderate (AHI 15 - <30) and severe

(AHI >30). The other parameters assessed by PSG were total

time of sleep, sleep efficiency, awaken time after sleep onset,

duration of REM sleep (NREM 1, 2 and 3), REM latency, REM

episodes, total duration of REM, episodes of micro-awakenings

CLINICAL AND POLYSOMNOGRAPHIC CHARACTERISTICS IN PATIENTS WITH MORNING HEADACHE

44 Headache Medicine, v.9, n.2, p.42-48, Apr./May/Jun. 2018

FRAGA TP, JALALI PS, FARO SANTOS PS, DE JESUS ACF.

and awakenings, average length of apneas/hypopneas,

basal pulse oximetry, desaturation ≥ under 4%, major

desaturation, period of time with desaturation <90%,

number of periodic movements members.

Statistical analysis

Variables were summarized by category as simple and

relative frequency, and with respective confidence intervals

when needed. Comparisons between the groups with and

without morning headache were conducted using chi-square

test and Fisher exact test. For evaluations of variables related

to a given proportion was used a binomial test. Analysis was

performed using SPSS version 15. The tests were considered

as two-tailed with significance level of p < 0.05.

RESULTS

The sample consisted of 108 patients, with a significantly

higher incidence of males (64.8%). In relation to the age, a

predominance of 31-60 years was found (63.9%;

p<0.0001), with ages up 30.9 and ≥60 years with 15.7%

values and 20.4%, respectively. Patients with normal body

mass index (BMI) represented 25.2% and 29.9% was

overweighed. However, the obese group surpassed (44.9%;

p>0.05). Sample diagnostic findings are shown in Table

1. In Group 1, almost 88% of the patients showed respiratory

sleep alterations against 81.3% in Group 2 (p>0.05).

The Group 1 (with morning headache) had 51.5%

(p=0.02) of female patients, with age predominance of

31-60 years (72.7%). Almost 47% of the patients had

BMI ≥30 Kg/m

. The Group 2 (no morning headache)

had 72% of men, with 60% of the patients aging between

31-60 years, and 44% was obese. The pathological

background and clinical picture of the sample are shown

in Tables 2 and 3. In Group 1, around 42% had upper

airway diseases, and almost 73% had complaints of anxiety,

and headache (45%), neurocognitive complaints (54%),

non-restorative sleep (82%) and insomnia (60.6%).

Related to the presence of morning headache, 33 patients

(30.6%) reported to be used suffering with it (CI 95%, 22.1-

40.2). Of this total, 51.5% were female (p= 0.02). Of the

33 patients with morning headache, four did not know or

did not want to report the characteristics of their headache

upon awakening. Of the 29 patients who responded

appropriately when asked about the duration of pain, a

homogeneous distribution among the options was found.

Around 52% of the patients reported 3-7 points in the visu-

al analogue scale (VAS) and 58.6% had morning headache

3-4 times a week (Table 4).

In Table 5 the polysomnography variables are listed in

more details. Among the characteristics surveyed, the only

variable with statistical significance was WASO (wake up

time after onset of sleep). Analyzing the WASO, 42.4% of

patients from Group 1 were in the range of normality, while

20% of patients from Group 2 were in that range (p=0.01).

Headache Medicine, v.9, n.2, p.42-48, Apr./May/Jun. 2018 45

CLINICAL AND POLYSOMNOGRAPHIC CHARACTERISTICS IN PATIENTS WITH MORNING HEADACHE

46 Headache Medicine, v.9, n.2, p.42-48, Apr./May/Jun. 2018

FRAGA TP, JALALI PS, FARO SANTOS PS, DE JESUS ACF.

DISCUSSION

The prevalence of morning headache in the average

population, according to Ohayon

(17)

and Ulfberg et al.

(18)

is 7.6% and 5%, respectively. In our study, the headache

upon awakening was reported by 30.6% of the sample.

This is according to the expectations, since the sample of

patients had various indications for polysomnography and

most of the patients had sleep-disordered breathing. In

patients with obstructive sleep apnea syndrome the morning

headache the prevalence rates ranged from 18

(17)

to 74%.

(19)

According to the American Academy of Sleep

Medicine,

(14)

the obstructive sleep apnea syndrome is a sleep

respiratory disorder characterized by recurrent episodes of

partial or total obstruction of the upper airway during sleep,

which lead to intermittent hypoxia, transient hypercapnia

and frequent awakenings, associated with clinical signs and/

or symptoms.

(20)

Among these, headache, especially the

morning headache, has been suggested as a clinical sign

found in OSA. However, many authors are questioning this

hypothesis.

(21)

The morning headache has been linked with other

sleep disorders, besides the OSA. Poceta et al.

reported

similar results in a retrospective study in which the incidence

of morning headache in patients with sleep apnea (24%)

was not significantly different from those with periodic limb

movements disorder (PLMD) and psychophysiological

insomnia. Göder et al.

found that a higher frequency of

morning headache in the sleep lab, not only in patients

with OSA, but also in patients with other sleep disorders,

compared to healthy subjects (25% versus 3%). In our study

we cannot conclude if there is difference in the prevalence

of morning headache complaint in the diagnosed sleep

disorders, because most of our patients had previous

diagnosis of some sleep breathing disorder.

Among patients with morning headache, there was a

predominance of females (p<0.05). This is not surprising,

since there are several reports in the literature of higher

prevalence of headache in women.

(5,24)

Stovner et al.

reported that 58% of women versus 41% of men in the

world present complaint of headaches.

In relation to clinical aspects, more than 43% of the

patients of our sample reported upper airways diseases.

This figure is high above the one of Alberti et al.

(19)

(26.3%;

p<0.05). In 2004, Ohayon et al.

(17)

concluded that

morning headache was a good indicator for mood disorders

and insomnia. Our study found that 60.6% (p<0.05) of

the patients complaining of morning headache presented

insomnia, corroborating with Ohayon et al.

(17)

However, a

little more than 21% (p>0.05) reported depression.

(23)

Göder

et al.

(23)

described 32% of patients with morning headache

presenting mood disorders. Almost 73% of our patients

presented anxiety disorder. Ohayon et al.

(17)

described that

anxiety and depression were significantly more prevalent

(28.5%) in patients with morning headache when compared

to the control group (5.5%).

According to Idiman et al.,

(25)

60% of patients with

OSA had headache. Alberti et al.

(19)

described 48.2% in

their sample, while in our study a rate of 45.5% was found.

Comparing the characteristics of morning headache,

a prevalence of moderate pain (51.7%) was seen related to

the data described by Goksan et al.

(26)

The latter reported a

moderate severity in 49.7% and light headache in 28.3%

of patients with OSA. Unlike Alberti et al.

(19)

who reported

that patients with OSA had morning headache of mild

intensity (>47%). When correlating duration and frequency

factors of Goksan et al.

(26)

headache lasted 1-4 hours

(37.5%) and >4 hours (35.8%), with month frequency of

9 to 15 times (34.9%) and >15 times (26.3%). Alberti et

al.

(19)

reported that in 47.4% pain lasted 2 hours and none

reported more than 5 hours of pain. Ten patients (52.6%)

had morning headache attacks 1-5 times a month.

Our patients presented homogeneous distribution

concerning to the duration and 58.6% reported frequency

of 3-4 episodes per week. It is important to note that our

sample was composed of patients with various sleep disorders,

however, 84 of 108 patients were diagnosed with obstructive

sleep apnea syndrome.

Göder et al.

(23)

studied patients with various sleep

disorders, and noted that the patients presenting morning

headaches showed decreased sleep efficiency. In our sample

no statistically significant difference between the two groups

was found.

Göder et al.

(23)

also described that patients with morning

headaches showed decrease in the proportion of REM sleep.

The authors suggest that this change in sleep architecture,

with reduction and fragmentation of sleep, can play a role

in the morning headache presented by patients with sleep

disorders. Aldrich and Chauncey

(27)

demonstrated that

patients with apnea/hypopnea index higher than 30 and

awakening headaches spent a significantly smaller

percentage of the total sleeping time in REM phase, when

compared with patients without morning headache. In our

study, both groups showed decreased REM sleep duration

(p > 0.05): with Group 1 (45.5%) and Group 2 (57.3%)

presenting less than 20% of total sleep time in REM. An

association between REM and the onset of chronic

paroxysmal hemicrania in headache and cluster headache

Headache Medicine, v.9, n.2, p.42-48, Apr./May/Jun. 2018 47

was also described.

(28)

Many possibilities can raise reasons

supporting the changes in REM as related to the symptoms

of headache. The decrease in REM phase may be

compensatory for the migraine onset in that same phase of

sleep. Alternatively, the REM fragmentation can play a role

by itself in the generation of migrane.

(29)

It is believed that the morning headache could be

related to a combination of mechanisms.

(30)

Among them,

a lower oxygen saturation and hypercapnia caused by

apnea episodes coud be triggering factors. Patients with

OSA often suffer desaturations in their sleep, and the

decrease of saturation may contribute to the complaints of

morning headache in this population of patients.

(19,30)

Our study did not find a relationship between complaints

of headache and blood oxygenation. Accordingly, Idiman et

al.

(25)

found no statistical significance between headache

and apnea/hypopnea or maximum desaturation in patients

with OSA. Aldrich and Chauncey

( 27)

described patients with

OSA and morning headache comparing with those without

morning headache, and found no difference on minimum

oxygen saturation during the night. These studies can raise

significant doubts on the hypothesis that the desaturation

could play a pathophysiological role in relationship between

morning headache and OSA.

According to the theories that support the relationship

between the commitment of the nocturnal oximetry and/or

sleep architecture and the presence of morning headache,

in theory our groups of patients should present a higher

incidence of morning headache. Whether considering the

possibility of a correlationship between variables and the

presence of headache upon awakening the patients from

Group 2 had a tendency to larger impairment of oxygen

saturation and sleep structure.

Therefore, in this study, we cannot conclude that only

the presence of the elevation of the apnea/hypopnea, a

relevant intermittent desaturation and the disorganization

of the structure of sleep were enough to modulate the

presence of morning headache. The difference of the greater

impairment of the architecture of sleep and nocturnal

oximetry, evidenced in Group 2, could be explained by the

higher incidence of patients with IAH > 30 in this sample

(33.3% vs. 18.2%). However, this difference was not

statistically significant.

CONCLUSION

The tendency to greater impairment of nocturnal

oximetry and the sleep architecture that occurred in Group

2 can arise some questionings: what are the factors that

truly determine the emergence of morning headache in

patients with sleep disorders? Would the clinical

characteristics help to identify the groups predisposed to

the manifestation of the headache? Analyzing our results,

one would see that the profile of previous pathological

conditions and complaints related to the sleep disorder are

different between the groups. Group 1 (morning headache)

was mainly composed by women with history of upper

airways diseases, anxiety, headache, complaints of insomnia,

and neurocognitive and non-restorative sleep difficulties.

This profile seems to expose a group particularly more

vulnerable to disturbances of sleep architecture and

desaturations at night. Therefore, it is possible that sleep

disorders are triggering factors in patients who have a

predisposition to the morning headache.

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Correspondence

Paulo Sergio Faro Santos

Departamento de Neurologia

Instituto de Neurologia de Curitiba

dr.paulo.faro@gmail.com

Recieved: June 22, 2018

Accepted: June 24, 2018

FRAGA TP, JALALI PS, FARO SANTOS PS, DE JESUS ACF.