Acta Neurol Scand 2014: 129 (Suppl. 198): 47–54 DOI: 10.1111/ane.12237
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Sleep quality and arousal in migraine and tension-type headache: the headache-sleep study Engstrøm M, Hagen K, Bjørk MH, Stovner LJ, Sand T. Sleep quality and arousal in migraine and tension-type headache: the headache-sleep study. Acta Neurol Scand: 2014: 129 (Suppl. 198): 47–54. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – The present paper summarizes and compares data from our studies on subjective and objective sleep quality and pain thresholds in tension-type headache (TTH), migraine, and controls. Material and methods – In a blinded controlled explorative study, we recorded polysomnography (PSG) and pressure, heat, and cold pain thresholds in 34 controls, 20 TTH, and 53 migraine patients. Sleep quality was assessed by questionnaires, sleep diaries, and PSG. Migraineurs who had their recordings more than 2 days from an attack were classified as interictal while the rest were classified as either preictal or postictal. Interictal migraineurs (n = 33) were also divided into two groups if their headache onsets mainly were during sleep and awakening (sleep migraine, SM), or during daytime and no regular onset pattern (non-sleep migraine, NSM). TTH patients were divided into a chronic or episodic group according to headache days per month. Results – Compared to controls, all headache groups reported more anxiety and sleep-related symptoms. TTH and NSM patients reported more daytime tiredness and tended to have lower pain thresholds. Despite normal sleep times in diary, TTH and NSM had increased slow-wave sleep as seen after sleep deprivation. Migraineurs in the preictal phase had shorter latency to sleep onset than controls. Except for a slight but significantly increased awakening index SM, patients differed little from controls in objective measurements. Conclusions – We hypothesize that TTH and NSM patients on the average need more sleep than healthy controls. SM patients seem more susceptible to sleep disturbances. Inadequate rest might be an attack-precipitating- and hyperalgesia-inducing factor.
Introduction
Sleep and headache are closely related (1–3). Many people have experienced that pain/headache can disturb sleep and conversely. Inadequate sleep can increase the risk of headache in general (2), can release headache (4), and can also reduce pain thresholds (5). Reduced pain threshold is found among headache patients compared to controls (6, 7). In migraine, several studies suggest that CNS excitability is changed in the preictal phase compared to the interictal phase, for example, for thermal PT (8). Detected similarities
M. Engstrøm1,2, K. Hagen1,3, M. H. Bjørk4,5, L. J. Stovner1,3, T. Sand1,2 1 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; 2 Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim, Norway; 3Norwegian National Headache Centre, St. Olavs Hospital, Trondheim, Norway; 4Department of Neurology, Haukeland University Hospital, Bergen, Norway; 5Department of Clinical Medicine, University of Bergen, Bergen, Norway
Key words: migraine; tension-type headache; sleep; polysomnography; arousal; pain thresholds M. Engstrøm, Department of Neuroscience, PB 8905, MTFS, Norwegian University of Science and Technology, N-7489 Trondheim, Norway Tel.: +47 72 57 50 90 Fax: +47 73 59 87 95 e-mail: [email protected] Accepted for publication November 10, 2013
and differences between controls, tension-type headache (TTH) patients, and migraineurs could be useful to clarify the relation between sleep, headache, and pain thresholds. As sleep disturbance is reported as a trigger for migraine and TTH, it may be of interest to study if sleep macro- and microstructure are disturbed in the headache-free phase, also compared to the preictal phase in migraine. If disturbed sleep is associated with PT reductions, presumably reflecting a central sensitization, this may clarify whether a sleep disturbance could be investigated further as a potential modifiable risk factor to achieve 47
Engstrøm et al. better headache prevention in future studies. Another specific hypothesis was that patients with nightly attacks have more disturbed sleep than those without nightly predilection. The present paper summarizes results on sleep and pain in a comprehensive controlled and blinded crosssectional study. Data have been reported as three different papers (9–11) on sleep and pain thresholds among healthy controls, TTH, and migraine patients. In addition, we also compare sleep in TTH and migraine patients for the first time in the present paper. As far as we know, no others have performed a blinded study and evaluated both sleep and pain thresholds in headache patients. Methods Participants
The method is described in detail elsewhere (9–11). One hundred and twenty-six persons, 85 women and 41 men, (age range 18–64, mean age 38.9 years), including 41 healthy controls, 24 TTH, and 61 migraine patients participated in this study (Fig. 1). They were mainly recruited by advertising in local newspapers for people between 18 and 65 years with and without headache. Potential participants with headache were diagnosed according to the ICHD-II criteria (12). Patients were selected if they had either (frequent) episodic TTH (1–14 headache days per month), chronic TTH (≥15 headache days per month), or migraine with two to six episodes per month with or without aura. Based on headache diaries, the date of the sleep recordings and pain threshold measurements migraine were divided into interictal (more than 2 days from an attack) and the rest were classified as either preictal or postictal
Figure 1. Numbers of participants in each group in the present study.
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(Fig. 2). Participants with and without aura were combined because few preictal and postictal patients were available. Patients were also categorized as having sleep-related migraine (SM) if usual attack onset was ‘upon awakening’ or during the night (‘waking me up’). Migraineurs who did not have SM were classified as having non-sleeprelated migraine (NSM). SM (n = 15) and NSM (n = 18) were analyzed in the interictal phase. Three migraine patients with midictal PSG, fulfilling both preictal and postictal criteria, were excluded from this analysis. Of 24 TTH patients, 20 were included while four were excluded owing to technical problems (battery error or lost electrodes, n = 2) or moderate or severe sleep apnea [apnea–hypopnea index (AHI) > 15 (n = 2)]. To preserve statistical power, as many persons as possible were kept in the control group, but to have comparable age/sex distributions, some female controls were randomly excluded from the TTH study. Pregnancy, major health problems, co-existing migraine, or frequent tension-type headache (TTH) were exclusion criteria. Painkillers or triptans for acute migraine were allowed. The study was approved by the regional ethics committee, and participants signed an informed consent before inclusion. Procedure
In a blinded controlled exploratory study, we recorded polysomnography. Recording details are presented elsewhere (9–11). All participants filled in sleep diaries 2 weeks before and 2 weeks after measurement of pain thresholds and subsequent polysomnography. Headache patients also filled in headache diaries for the same period. Every subject answered several questionnaires including: Epworth Sleepiness Scale (13), questions adapted from Karolinska Sleep Questionnaire (14), Pittsburgh Sleep Quality Index (PSQI) (15), Hospital Anxiety and Depression Subscales (16), and 10 questions from the Autonomic Symptom Profile (17, 18). As a supplement to the Epworth
Figure 2. The relationship between the nearest migraine attack (lightening Z symbol) and the classification of the recording as interictal, preictal, or postictal.
The headache-sleep study Sleepiness Scale, they also answered the question: ‘Do you have bothersome tiredness during daytime?’(No(0)-Daily(4)). Patients and controls underwent a full-night ambulatory sleep study unattended in our patient hotel. The participants were instructed to go to bed, sleep as normal, and register lights-off, lights-on, and sleep times in sleep diaries. Automatic analysis was applied for leg movements. Respiration was scored according to modified ‘Chicago criteria’ (19). Sleep staging was performed according to ‘The AASM Manual for the scoring of sleep and associated events’ from 2007 (20) with a few exceptions, as described below. First, fast arousal was defined according to the AASM manual (20) as an abrupt shift of EEG frequency (alpha, theta, and/or faster than 16 Hz activity) lasting 3–30 s, separated with at least 10 s of sleep. We also scored D- and Kbursts (21). Thermal pain thresholds (difference from 32°C baseline) and pressure pain thresholds (algometry) were recorded before the participants had their PSG equipment mounted. Heat and cold pain thresholds were measured on thenar and the medial forehead on both sides. Pressure pain thresholds were measured at four sites bilaterally in a fixed order. We used regional mean values for heat, cold, and pressure PT. Technicians and scorers of PSG and pain threshold measurements were blinded for diagnoses. Statistics
Statistical analyses were performed with PASW statistics v.18 and SYSTAT version 11. Univariate two-group comparisons were made by non-
parametric Mann–Whitney U-tests. Categorical data were analyzed with Pearson chi-square test or Fisher’s exact test. The primary comparisons reported in this paper will be: (i) controls vs TTH, interictal NSM, and interictal SM, (ii) between total migraine interictal and preictal groups, and (iii) TTH vs the whole migraine group and interictal migraineurs, both sleep- and non-sleep-related migraine subgroups. Post hoc we also compared PSG data on sleep TTH and non-sleep TTH patients, classified in the same way as migraineurs. Results
The most important numerical results have been reported in Tables 1 and 2. TTH as well as interictal migraineurs (both SM and NSM patients) reported more anxiety symptoms in HADS (≥5.3 vs ≤3.0, P < 0.01) and higher autonomic index score (≥5.2 vs ≤4.3, P < 0.001), more symptoms of insomnia (Karolinska Sleep Questionnaire insomnia score ≥5.8 vs 3.4, P < 0.01), more symptoms in PSQIgs (5.9 vs 3.8, P < 0.001), and more pain-related sleep trouble in PSQI than controls (Tables 1 and 3). TTH patients had more symptoms of insomnia and more subjective tiredness than migraineurs (Table 1). Both TTH and NSM patients had more slowwave sleep than controls (≥104 vs ≤86 min, P < 0.05), less fast arousals (≥18.3 vs ≤15.5 per hour, P < 0.05), and more frequent daytime tiredness (0–4) (≥1.3 vs 0.7 P < 0.01). NSM also had lower thermal pain thresholds than controls (heat pain thresholds 11.2°C vs 16.6°C, cold pain thresholds 16.1°C vs 20.7°C, P < 0.05). Among TTH, only chronic TTH had lower pressure pain
Table 1 Population, sleep diary, questionnaire, and headache-related data for all patients : counts or mean (SD)
Age (years) Sex: F/M Headache frequency (1–4) Headache intensity (1–4) Headache history duration (years) Average diary sleep time (hour) Long awakenings in diary (no) Daytime tiredness frequency (0–4) Insomnia KSQ score (0–16)1 Pain-related sleep trouble (1–4)2 Autonomic index (0–30)4 PSQIgs (0–21)2 HADS anxiety score (0–21)3 Insomnia KSQ score (0–16)1
Controls for migraine (n = 34)
Controls for TTH (n = 29)
Migraine (n = 53)
Tension-type headache (n = 20)
39.6 (13.7) 20/14 NA NA NA 7.3 (0.8) 0.1 (0.2) 0.7 (0.8) 3.4 (2.3) 3.8 (2.6) 1.3 (0.7) 1.5 (1.4) 1.6 (2.1) 2.9 (2.6)
41.2 (13.6) 15/14 NA NA NA 7.2 (0.8) 0.1 (0.2) 0.7 (0.9) 3.4 (2.4) 3.9 (2.7) 1.3 (0.6) 1.4 (1.4) 1.5 (2.2) 3.0 (2.8)
38.2 (12.0) 41/12 2.2 (0.7) 2.5 (0.5) 21.6 (13.8) 7.2 (1.0) 0.4 (0.8) 1.1 (0.9) 6.1 (2.9) 6.3 (3.2) 1.9 (1.0) 6.6 (4.4) 2.3 (2.3) 5.4 (3.1)
40.9 (13.5) 11/9 3.5 (0.7)5 1.5 (0.5) 15.8 (12.2) 6.8 (1.1) 0.4 (0.4) 1.7 (1.0)6 7.9 (2.4)7 7.2 (3.2) 2.0 (1.0) 5.3 (3.5) 2.8 (3.0) 5.9 (3.0)
1
Sum of four insomnia questions in Karolinska Sleep Questionnaire (KSQ); 2Pittsburgh Sleep Quality Index Global Score; 3Sum of seven questions about anxiety symptoms during the last week from the Hospital Anxiety and Depression Scale Questionnaire; 4Sum of ten questions about autonomic instability during the last year. Tension-type headache was compared statistically to migraine: Mann–Whitney U-test: 5P < 0.0005, 6P < 0.05, 7P = 0.006. Significant differences are shown in bold.
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Engstrøm et al. Table 2 Polysomnography and pain threshold mean values (SD) for controls, interictal migraineurs, with sleep migraine and non-sleep migraine subgroups, and tensiontype headache Controls6 (n = 34) Total sleep time (min) Sleep efficiency (%) Awakening index (no/h) Stage 1 (min) Stage 2 (min) Stage 3 (min) REM (min) AASM arousal index (per hour)1 D-burst index (per hour)2 K-burst index (per hour)2 Pressure pain threshold (kPa)4 Heat pain threshold (°C)3 Cold pain threshold (°C)3
409 90.0 0.99 27 197 86 99 18.3 11.8 3.0 661 13.4 20.8
Migraine (n = 33)
(68) (8.1) (0.59) (19) (47) (31) (26) (5.7) (8.0) (3.8) (249) (3.1) (6.3)
435 91.0 1.27 32 201 97 106 16.3 9.5 3.3 549 11.7 17.2
Sleep migraine (n = 15)
(61) (6.1) (0.74) (15) (44) (28) (35) (9.1) (7.5) (2.5) (135) (3.6) (6.9)
417 89.4 1.45 35 194 88 99 17.4 7.3 2.4 586 12.4 18.4
(67) (7.6) (0.84) (17) (44) (25)5 (38) (8.6) (5.7) (2.2) (141) (3.3) (6.3)
Non-sleep migraine (n = 18) 451 92.4 1.12 29 206 104 112 15.5 11.3 4.0 519 11.0 16.2
(52) (4.2) (0.63) (13) (45) (28) (32) (9.7) (8.3) (2.5) (125) (3.8) (7.3)
Tension-type headache (n = 20) 432 91.2 1.1 29 185 107 111 14.5 7.9 3.7 543 12.7 19.4
(46) (5.6) (0.6) (15) (34) (21)5 (30) (4.3) (6.3) (4.5) (191) (3.7) (7.4)
1
Fast EEG arousal; 2Slow EEG arousal; 3Expressed as the difference above/below the 32°C baseline; 4Mean from four bilateral sites. Tension-type headache was compared statistically to migraine, sleep migraine, and non-sleep migraine; 5Mann–Whitney U-test: P = 0.026; 6Control group for migraine. Significant differences are shown in bold.
thresholds than controls (506 vs 678 kPa) (P < 0.05) (Table 3). Non-sleep migraine patients spent more time in bed (488 vs 453 min, P < 0.05) and had more K-bursts (4.0 vs 3.0 per hour, P < 0.05) than controls. SM patients also had less D-bursts (7.3 vs 11.8 per hour, P < 0.05), more awakenings (1.45 vs 0.99 per hour, P < 0.05), and tended to have more N1 sleep than controls (35 vs 27 min, P = 0.05). Sleep migraine patients had less slow-wave sleep (88 vs 104 min, P < 0.05) and less K-bursts (2.4 vs 4.0 per hour, P < 0.05) than NSM patients and less slow-wave sleep than TTH patients (P = 0.026) (Table 2). Table 3 Summed main results for tension-type headache (TTH) patients, migraineurs in interictal (MI), and preictal (MP) phases or sleep- and non-sleep (SM and NSM)1 migraineurs compared to controls (C) Report data Anxiety symptoms2 Insomnia symptoms3 Subjective sleep disturbances4 Total sleep time (diary) Subjective daytime tiredness5 Examination data Awake index (>8 Hz, >30 s, per hour) N3, slow-wave sleep, minutes Fast arousals (lasting 3–30 s) Pressure pain thresholds (kPa)6 Thermal pain thresholds (°C)7 Latency to sleep onset 1
C C C C C
< < < =
TTH**/NSM* C > TTH(*)/NSM(*) C < NSM* MP < MI**
Both NSM and SM patients were in the interictal phase; 2Sum of seven questions about anxiety symptoms during the last week from the Hospital Anxiety and Depression Scale Questionnaire; 3Sum of insomnia questions in Karolinska Sleep Questionnaire; 4Evaluated by Pittsburgh sleep quality and questions adapted from the Karolinska Sleep Questionnaire; 5Question: Do you have bothersome tiredness during daytime? (0(no)-4(daily)); 6Mean value of m. temporalis, m. splenius, m. trapezius, distal dorsal middle finger, three tests on each place, both left and right side; 7Mean value heat and cold pain thresholds for frontal and thenar region, three tests on each side; Mann–Whitney U-test: (*)P = 0.05, *P < 0.05, **P < 0.01, ***P < 0.001.
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Preictal migraineurs had shorter latency to sleep onset than interictal migraineurs (2.0 vs 10.3 min, P < 0.01). Thermal pain thresholds were lower in interictal migraine compared to controls (P < 0.04). Only five sleep TTH patients were available. However, also non-sleep TTH (n = 15) had less fast arousals than sleep TTH patients (P < 0.05). Discussion
The major findings of the present study are (i) Patients with TTH report more insomnia than migraine patients; (ii) Patients with TTH and migraine report lower sleep quality and more insomnia, tiredness, and autonomic symptoms than controls; and (iii) In PSG, NSM and TTH patients had more slow-wave (N3) sleep than controls, that is, better sleep quality, which seemingly stood in contrast to the fact that they also reported more frequent daytime tiredness and tended to have reduced pain thresholds. We hypothesize that the latter findings are explained by a relative sleep deficit caused by a higher need of sleep in TTH and NSM patients. Subjective and objective sleep quality in controls and headache patients
Increased symptoms of anxiety, insomnia, and subjective tiredness among migraineurs and TTH patients have also been found by others (1, 22). Compared to controls, the reduced subjective sleep quality in headache patients was most striking. PSG sleep parameters differed, and although this difference was less striking, it seemed paradoxical compared to controls. Mean total sleep time in diaries did not differ between
The headache-sleep study Table 4 Comparison and interpretation of important symptoms and objective findings for the TTH, NSM, and SM patients compared to controls Group Sleep migraineurs Non-sleep migraineurs Tension-type headache
Summary of findings
Interpretation
Number of awakenings ↑, amount of superficial sleep (↑), but not increased daytime tiredness or sleepiness Slow-wave sleep ↑, fast arousals ↓, increased frequency of daytime tiredness, and reduced pain thresholds Slow-wave sleep ↑, increased frequency of daytime tiredness and tendency to reduced pressure pain thresholds
the groups (Table 2). It has been shown that a history of chronic insomnia does not predict poor EEG sleep (23). However, increased slow-wave sleep, as found in the present study among TTH and NSM patients, is one factor that usually indicates better sleep quality (24). Reduced amounts of fast arousals and increased slow-wave activity have also been found the night after experimental sleep deprivation (25) and are in line with what we found in TTH and NSM patients. After foregoing sleep deprivation, a ‘hypoarousal state’ with reduced fast arousals, increased slow-wave sleep, and increased daytime tiredness can be regarded as normal. However, in the present study, sleep diaries revealed normal average total sleep times before the PSG. Hence, the NSM and TTH patients seem to have a hypo-arousal state possibly related to a relative sleep deprivation caused by increased need for sleep. This hypothesis is consistent with the notion that EEG among migraineurs is found to be either normal or have subtle findings that may reflect drowsiness (26). Furthermore, among migraineurs, the sleepiness was even more increased in the preictal phase as mean sleep onset latency was reduced compared to interictal phase. Increased objective sleepiness in the preictal phase is consistent with subjective symptoms of drowsiness (27) and with objective EEG findings of slow activity preictally (28). However, our PSG findings differ from Karthik et al. (29) who demonstrated longer latency to sleep onset and less NREM sleep among migraineurs. Methodological differences such as patient selection might explain divergent results. SM patients differed from NSM and TTH patients by having reduced sleep quality in PSG (more awakenings than controls and less slowwave sleep than TTH and NSM). Hence, SM was the only group with an ‘objective parallel’ to their reported sleep disturbance. Lower index of slow EEG bursts in NREM and high-frequency EEG arousals during REM sleep have previously been found among interictal SM patients (30). These findings have been interpreted as hypofunction of the arousal system (30). In the present study,
Reduced sleep quality, preserved arousal system, or hyperarousal? Increased sleep need, recovery sleep, increased sleep quality, hypo-arousal? Increased sleep need, recovery sleep, increased sleep quality, hypo-arousal?
signs of hypo-arousability were prominent among the NSM, but not among the SM patients. The relatively few sleep TTH patients did probably not have a significant effect on the main results, but a post hoc comparison showed that also nonsleep TTH patients had less fast arousals than sleep TTH patients. Accordingly, we hypothesize that the hypo-arousability observed among the NSM and TTH patients (mainly non-sleep TTH) may be related to a relative sleep deprivation and that these patients also may need more sleep than healthy controls (Table 4). Pain and sleep
We found decreased thermal pain thresholds in the NSM and reduced pressure pain thresholds in chronic TTH patients in concert with other studies (7, 31). Reduced pain thresholds have also been found among healthy volunteers after sleep deprivation (5). Migraineurs with head allodynia during attack also report more sleep disturbances than non-allodynic migraineurs when compared to controls (32). In the present study, PSG and pain threshold findings among NSM and TTH (mostly non-sleep TTH) patients are in principle similar. These findings, together with normal average sleep times, are also consistent with a relative sleep deprivation (5). Preictal reduction in sleep onset latency in the present study and preictal heat pain threshold reduction in a previous study (8) are also compatible with sleep deprivation as a headache trigger. However, among SM patients in the present study, disturbed sleep in PSG, probably disposing for sleep deprivation, was not accompanied by reduced daytime vigilance or reduction in pain thresholds. Hence, we hypothesize that arousability is constitutionally different in our groups: decreased in NSM (and TTH) and conserved in SM patients. Arousability can in fact be associated with autonomic activity and possibly explains pain threshold changes. Indeed, arousability has been linked to hypertension (33) while high blood pressure also seems to be associated with hypo-algesia (34). 51
Engstrøm et al. Headache onset time
The NSM and TTH patients had quite corresponding results, possibly because the majority of our TTH patients were non-sleep TTH. This interesting finding suggests that sleep and attackprecipitating mechanisms are similar across different headache diagnoses. Hence, the increased combined load of affective and sleep-related symptoms might be the main etiological factor for headache. If so, the individual headache onset time may only depend on which ‘drop’ that made the flood. Increased susceptibility to daytime load and subsequently increased need for sleep are probably characteristic for headaches that tend to start during daytime, while increased susceptibility to sleep disturbances probably is characteristic when headache begins during sleep. However, in the present study compared to migraineurs the TTH group had a higher headache frequency and, not surprisingly, headache was accompanied by increased insomnia symptoms. The SM group had no signs indicating sleep deprivation per se according to the sleep diary, PSG, daytime tiredness score, and pain thresholds. However, disturbed sleep could increase the risk for sleep deprivation (35), and symptoms related to sleep, anxiety, and autonomic activity among SM did not differ from other headache groups. The latter signs might be part of what make TTH and NSM patients wearier and increase the sleep need (Fig. 3). Hence, we hypothesize that SM patients have a more robust arousal system than NSM and TTH. SM patients may even be in a hyperarousal state. We could not detect differences in sleep disturbing parameters (AHI and PLM indexes) between SM patients and NSM or controls. A susceptibility to clinically nonsignificant sleep disturbances might be a disadvantage of a robust arousal system. This notion is in concert with the observed increase of SM by age as sleep gets lighter with increasing age (36). One might speculate that the difference in arousability between the groups with attack onset during awake hours and during sleep is related to the periaqueductal gray (PAG) matter as ‘hyperarousal’ and ‘hypoarousal’ have been related to ventrolateral and lateral/dorsal PAG regions, respectively (37). Strengths and limitations
The blinded and controlled cross-sectional study design increases the probability for valid results. Furthermore, the participants were mainly recruited by advertising in local newspapers, in 52
Figure 3. Hypothesized different nervous system responses to increased daily life strain.
contrast to a hospital-based migraine population which may include more severe and long-standing cases. On the other hand, the selection of headache patients responding to a newspaper advertisement may not be fully representative for the whole headache population. It is evidently impossible to recruit a completely unbiased patient population. However, as most migraine patients had been prescribed triptans for their attacks and because headache history and headache intensity were comparable to a previous hospital-based population (38), our study groups were probably fairly representative for a patient group encountered in a clinical setting. A study design with repeated PSGs may be more powerful for the detection of phase-related differences. Individualized matched controls for age and sex would have been preferable rather than a comparable control group. A slight underestimation of sleep problems is expected in our study because patients with known and diagnosed previous sleep disorders were excluded; however, this exclusion is a strength regarding the major aims of the study. This study was exploratory, and we did not adjust for multiple comparisons because we did not want to increase type II failures on the cost of reducing type I failures (39). The possibility of both type I and type II errors is acknowledged. Independent replication of our results is accordingly needed. Conclusions
We have unified and compared data reported in three papers (9–11), we conclude that all our headache groups reported more anxiety and sleep-related symptoms than controls. Even though average total sleep times in TTH (mainly non-sleep TTH) and interictal NSM patients were normal, they had objective and subjective signs consistent with a hypo-arousal state consistent
The headache-sleep study with foregoing sleep deprivation. SM patients had findings in PSG consistent with disturbed and lighter sleep, but they paradoxically did not report more frequent daytime tiredness. The SM patients seemed to have a more robust arousability, possibly making them more susceptible for sleep disturbing factors like hypopneas or PLMs within the normal range. The combined results from these studies suggest that there are subgroups within both the tension-type headache and the migraine group in which sleep patterns and attack-precipitating mechanisms are different. However, the TTH and NSM subgroups had very similar sleep and pain thresholds suggesting the presence of common attack-initiating mechanisms across headache disorder boundaries. Acknowledgments We thank Grethe Helde, Marit Stjern, and Gøril Bruvik Gravdahl for practical assistance. This study was supported by grant from Department of Neuroscience; Norwegian University of Science and Technology, and Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU). Trondheim, Norway.
Conflict of interest None.
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© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Sleep quality and arousal in migraine and tension-type headache: the headache-sleep study Engstrøm M, Hagen K, Bjørk MH, Stovner LJ, Sand T. Sleep quality and arousal in migraine and tension-type headache: the headache-sleep study. Acta Neurol Scand: 2014: 129 (Suppl. 198): 47–54. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – The present paper summarizes and compares data from our studies on subjective and objective sleep quality and pain thresholds in tension-type headache (TTH), migraine, and controls. Material and methods – In a blinded controlled explorative study, we recorded polysomnography (PSG) and pressure, heat, and cold pain thresholds in 34 controls, 20 TTH, and 53 migraine patients. Sleep quality was assessed by questionnaires, sleep diaries, and PSG. Migraineurs who had their recordings more than 2 days from an attack were classified as interictal while the rest were classified as either preictal or postictal. Interictal migraineurs (n = 33) were also divided into two groups if their headache onsets mainly were during sleep and awakening (sleep migraine, SM), or during daytime and no regular onset pattern (non-sleep migraine, NSM). TTH patients were divided into a chronic or episodic group according to headache days per month. Results – Compared to controls, all headache groups reported more anxiety and sleep-related symptoms. TTH and NSM patients reported more daytime tiredness and tended to have lower pain thresholds. Despite normal sleep times in diary, TTH and NSM had increased slow-wave sleep as seen after sleep deprivation. Migraineurs in the preictal phase had shorter latency to sleep onset than controls. Except for a slight but significantly increased awakening index SM, patients differed little from controls in objective measurements. Conclusions – We hypothesize that TTH and NSM patients on the average need more sleep than healthy controls. SM patients seem more susceptible to sleep disturbances. Inadequate rest might be an attack-precipitating- and hyperalgesia-inducing factor.
Introduction
Sleep and headache are closely related (1–3). Many people have experienced that pain/headache can disturb sleep and conversely. Inadequate sleep can increase the risk of headache in general (2), can release headache (4), and can also reduce pain thresholds (5). Reduced pain threshold is found among headache patients compared to controls (6, 7). In migraine, several studies suggest that CNS excitability is changed in the preictal phase compared to the interictal phase, for example, for thermal PT (8). Detected similarities
M. Engstrøm1,2, K. Hagen1,3, M. H. Bjørk4,5, L. J. Stovner1,3, T. Sand1,2 1 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; 2 Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim, Norway; 3Norwegian National Headache Centre, St. Olavs Hospital, Trondheim, Norway; 4Department of Neurology, Haukeland University Hospital, Bergen, Norway; 5Department of Clinical Medicine, University of Bergen, Bergen, Norway
Key words: migraine; tension-type headache; sleep; polysomnography; arousal; pain thresholds M. Engstrøm, Department of Neuroscience, PB 8905, MTFS, Norwegian University of Science and Technology, N-7489 Trondheim, Norway Tel.: +47 72 57 50 90 Fax: +47 73 59 87 95 e-mail: [email protected] Accepted for publication November 10, 2013
and differences between controls, tension-type headache (TTH) patients, and migraineurs could be useful to clarify the relation between sleep, headache, and pain thresholds. As sleep disturbance is reported as a trigger for migraine and TTH, it may be of interest to study if sleep macro- and microstructure are disturbed in the headache-free phase, also compared to the preictal phase in migraine. If disturbed sleep is associated with PT reductions, presumably reflecting a central sensitization, this may clarify whether a sleep disturbance could be investigated further as a potential modifiable risk factor to achieve 47
Engstrøm et al. better headache prevention in future studies. Another specific hypothesis was that patients with nightly attacks have more disturbed sleep than those without nightly predilection. The present paper summarizes results on sleep and pain in a comprehensive controlled and blinded crosssectional study. Data have been reported as three different papers (9–11) on sleep and pain thresholds among healthy controls, TTH, and migraine patients. In addition, we also compare sleep in TTH and migraine patients for the first time in the present paper. As far as we know, no others have performed a blinded study and evaluated both sleep and pain thresholds in headache patients. Methods Participants
The method is described in detail elsewhere (9–11). One hundred and twenty-six persons, 85 women and 41 men, (age range 18–64, mean age 38.9 years), including 41 healthy controls, 24 TTH, and 61 migraine patients participated in this study (Fig. 1). They were mainly recruited by advertising in local newspapers for people between 18 and 65 years with and without headache. Potential participants with headache were diagnosed according to the ICHD-II criteria (12). Patients were selected if they had either (frequent) episodic TTH (1–14 headache days per month), chronic TTH (≥15 headache days per month), or migraine with two to six episodes per month with or without aura. Based on headache diaries, the date of the sleep recordings and pain threshold measurements migraine were divided into interictal (more than 2 days from an attack) and the rest were classified as either preictal or postictal
Figure 1. Numbers of participants in each group in the present study.
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(Fig. 2). Participants with and without aura were combined because few preictal and postictal patients were available. Patients were also categorized as having sleep-related migraine (SM) if usual attack onset was ‘upon awakening’ or during the night (‘waking me up’). Migraineurs who did not have SM were classified as having non-sleeprelated migraine (NSM). SM (n = 15) and NSM (n = 18) were analyzed in the interictal phase. Three migraine patients with midictal PSG, fulfilling both preictal and postictal criteria, were excluded from this analysis. Of 24 TTH patients, 20 were included while four were excluded owing to technical problems (battery error or lost electrodes, n = 2) or moderate or severe sleep apnea [apnea–hypopnea index (AHI) > 15 (n = 2)]. To preserve statistical power, as many persons as possible were kept in the control group, but to have comparable age/sex distributions, some female controls were randomly excluded from the TTH study. Pregnancy, major health problems, co-existing migraine, or frequent tension-type headache (TTH) were exclusion criteria. Painkillers or triptans for acute migraine were allowed. The study was approved by the regional ethics committee, and participants signed an informed consent before inclusion. Procedure
In a blinded controlled exploratory study, we recorded polysomnography. Recording details are presented elsewhere (9–11). All participants filled in sleep diaries 2 weeks before and 2 weeks after measurement of pain thresholds and subsequent polysomnography. Headache patients also filled in headache diaries for the same period. Every subject answered several questionnaires including: Epworth Sleepiness Scale (13), questions adapted from Karolinska Sleep Questionnaire (14), Pittsburgh Sleep Quality Index (PSQI) (15), Hospital Anxiety and Depression Subscales (16), and 10 questions from the Autonomic Symptom Profile (17, 18). As a supplement to the Epworth
Figure 2. The relationship between the nearest migraine attack (lightening Z symbol) and the classification of the recording as interictal, preictal, or postictal.
The headache-sleep study Sleepiness Scale, they also answered the question: ‘Do you have bothersome tiredness during daytime?’(No(0)-Daily(4)). Patients and controls underwent a full-night ambulatory sleep study unattended in our patient hotel. The participants were instructed to go to bed, sleep as normal, and register lights-off, lights-on, and sleep times in sleep diaries. Automatic analysis was applied for leg movements. Respiration was scored according to modified ‘Chicago criteria’ (19). Sleep staging was performed according to ‘The AASM Manual for the scoring of sleep and associated events’ from 2007 (20) with a few exceptions, as described below. First, fast arousal was defined according to the AASM manual (20) as an abrupt shift of EEG frequency (alpha, theta, and/or faster than 16 Hz activity) lasting 3–30 s, separated with at least 10 s of sleep. We also scored D- and Kbursts (21). Thermal pain thresholds (difference from 32°C baseline) and pressure pain thresholds (algometry) were recorded before the participants had their PSG equipment mounted. Heat and cold pain thresholds were measured on thenar and the medial forehead on both sides. Pressure pain thresholds were measured at four sites bilaterally in a fixed order. We used regional mean values for heat, cold, and pressure PT. Technicians and scorers of PSG and pain threshold measurements were blinded for diagnoses. Statistics
Statistical analyses were performed with PASW statistics v.18 and SYSTAT version 11. Univariate two-group comparisons were made by non-
parametric Mann–Whitney U-tests. Categorical data were analyzed with Pearson chi-square test or Fisher’s exact test. The primary comparisons reported in this paper will be: (i) controls vs TTH, interictal NSM, and interictal SM, (ii) between total migraine interictal and preictal groups, and (iii) TTH vs the whole migraine group and interictal migraineurs, both sleep- and non-sleep-related migraine subgroups. Post hoc we also compared PSG data on sleep TTH and non-sleep TTH patients, classified in the same way as migraineurs. Results
The most important numerical results have been reported in Tables 1 and 2. TTH as well as interictal migraineurs (both SM and NSM patients) reported more anxiety symptoms in HADS (≥5.3 vs ≤3.0, P < 0.01) and higher autonomic index score (≥5.2 vs ≤4.3, P < 0.001), more symptoms of insomnia (Karolinska Sleep Questionnaire insomnia score ≥5.8 vs 3.4, P < 0.01), more symptoms in PSQIgs (5.9 vs 3.8, P < 0.001), and more pain-related sleep trouble in PSQI than controls (Tables 1 and 3). TTH patients had more symptoms of insomnia and more subjective tiredness than migraineurs (Table 1). Both TTH and NSM patients had more slowwave sleep than controls (≥104 vs ≤86 min, P < 0.05), less fast arousals (≥18.3 vs ≤15.5 per hour, P < 0.05), and more frequent daytime tiredness (0–4) (≥1.3 vs 0.7 P < 0.01). NSM also had lower thermal pain thresholds than controls (heat pain thresholds 11.2°C vs 16.6°C, cold pain thresholds 16.1°C vs 20.7°C, P < 0.05). Among TTH, only chronic TTH had lower pressure pain
Table 1 Population, sleep diary, questionnaire, and headache-related data for all patients : counts or mean (SD)
Age (years) Sex: F/M Headache frequency (1–4) Headache intensity (1–4) Headache history duration (years) Average diary sleep time (hour) Long awakenings in diary (no) Daytime tiredness frequency (0–4) Insomnia KSQ score (0–16)1 Pain-related sleep trouble (1–4)2 Autonomic index (0–30)4 PSQIgs (0–21)2 HADS anxiety score (0–21)3 Insomnia KSQ score (0–16)1
Controls for migraine (n = 34)
Controls for TTH (n = 29)
Migraine (n = 53)
Tension-type headache (n = 20)
39.6 (13.7) 20/14 NA NA NA 7.3 (0.8) 0.1 (0.2) 0.7 (0.8) 3.4 (2.3) 3.8 (2.6) 1.3 (0.7) 1.5 (1.4) 1.6 (2.1) 2.9 (2.6)
41.2 (13.6) 15/14 NA NA NA 7.2 (0.8) 0.1 (0.2) 0.7 (0.9) 3.4 (2.4) 3.9 (2.7) 1.3 (0.6) 1.4 (1.4) 1.5 (2.2) 3.0 (2.8)
38.2 (12.0) 41/12 2.2 (0.7) 2.5 (0.5) 21.6 (13.8) 7.2 (1.0) 0.4 (0.8) 1.1 (0.9) 6.1 (2.9) 6.3 (3.2) 1.9 (1.0) 6.6 (4.4) 2.3 (2.3) 5.4 (3.1)
40.9 (13.5) 11/9 3.5 (0.7)5 1.5 (0.5) 15.8 (12.2) 6.8 (1.1) 0.4 (0.4) 1.7 (1.0)6 7.9 (2.4)7 7.2 (3.2) 2.0 (1.0) 5.3 (3.5) 2.8 (3.0) 5.9 (3.0)
1
Sum of four insomnia questions in Karolinska Sleep Questionnaire (KSQ); 2Pittsburgh Sleep Quality Index Global Score; 3Sum of seven questions about anxiety symptoms during the last week from the Hospital Anxiety and Depression Scale Questionnaire; 4Sum of ten questions about autonomic instability during the last year. Tension-type headache was compared statistically to migraine: Mann–Whitney U-test: 5P < 0.0005, 6P < 0.05, 7P = 0.006. Significant differences are shown in bold.
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Engstrøm et al. Table 2 Polysomnography and pain threshold mean values (SD) for controls, interictal migraineurs, with sleep migraine and non-sleep migraine subgroups, and tensiontype headache Controls6 (n = 34) Total sleep time (min) Sleep efficiency (%) Awakening index (no/h) Stage 1 (min) Stage 2 (min) Stage 3 (min) REM (min) AASM arousal index (per hour)1 D-burst index (per hour)2 K-burst index (per hour)2 Pressure pain threshold (kPa)4 Heat pain threshold (°C)3 Cold pain threshold (°C)3
409 90.0 0.99 27 197 86 99 18.3 11.8 3.0 661 13.4 20.8
Migraine (n = 33)
(68) (8.1) (0.59) (19) (47) (31) (26) (5.7) (8.0) (3.8) (249) (3.1) (6.3)
435 91.0 1.27 32 201 97 106 16.3 9.5 3.3 549 11.7 17.2
Sleep migraine (n = 15)
(61) (6.1) (0.74) (15) (44) (28) (35) (9.1) (7.5) (2.5) (135) (3.6) (6.9)
417 89.4 1.45 35 194 88 99 17.4 7.3 2.4 586 12.4 18.4
(67) (7.6) (0.84) (17) (44) (25)5 (38) (8.6) (5.7) (2.2) (141) (3.3) (6.3)
Non-sleep migraine (n = 18) 451 92.4 1.12 29 206 104 112 15.5 11.3 4.0 519 11.0 16.2
(52) (4.2) (0.63) (13) (45) (28) (32) (9.7) (8.3) (2.5) (125) (3.8) (7.3)
Tension-type headache (n = 20) 432 91.2 1.1 29 185 107 111 14.5 7.9 3.7 543 12.7 19.4
(46) (5.6) (0.6) (15) (34) (21)5 (30) (4.3) (6.3) (4.5) (191) (3.7) (7.4)
1
Fast EEG arousal; 2Slow EEG arousal; 3Expressed as the difference above/below the 32°C baseline; 4Mean from four bilateral sites. Tension-type headache was compared statistically to migraine, sleep migraine, and non-sleep migraine; 5Mann–Whitney U-test: P = 0.026; 6Control group for migraine. Significant differences are shown in bold.
thresholds than controls (506 vs 678 kPa) (P < 0.05) (Table 3). Non-sleep migraine patients spent more time in bed (488 vs 453 min, P < 0.05) and had more K-bursts (4.0 vs 3.0 per hour, P < 0.05) than controls. SM patients also had less D-bursts (7.3 vs 11.8 per hour, P < 0.05), more awakenings (1.45 vs 0.99 per hour, P < 0.05), and tended to have more N1 sleep than controls (35 vs 27 min, P = 0.05). Sleep migraine patients had less slow-wave sleep (88 vs 104 min, P < 0.05) and less K-bursts (2.4 vs 4.0 per hour, P < 0.05) than NSM patients and less slow-wave sleep than TTH patients (P = 0.026) (Table 2). Table 3 Summed main results for tension-type headache (TTH) patients, migraineurs in interictal (MI), and preictal (MP) phases or sleep- and non-sleep (SM and NSM)1 migraineurs compared to controls (C) Report data Anxiety symptoms2 Insomnia symptoms3 Subjective sleep disturbances4 Total sleep time (diary) Subjective daytime tiredness5 Examination data Awake index (>8 Hz, >30 s, per hour) N3, slow-wave sleep, minutes Fast arousals (lasting 3–30 s) Pressure pain thresholds (kPa)6 Thermal pain thresholds (°C)7 Latency to sleep onset 1
C C C C C
< < < =
TTH**/NSM* C > TTH(*)/NSM(*) C < NSM* MP < MI**
Both NSM and SM patients were in the interictal phase; 2Sum of seven questions about anxiety symptoms during the last week from the Hospital Anxiety and Depression Scale Questionnaire; 3Sum of insomnia questions in Karolinska Sleep Questionnaire; 4Evaluated by Pittsburgh sleep quality and questions adapted from the Karolinska Sleep Questionnaire; 5Question: Do you have bothersome tiredness during daytime? (0(no)-4(daily)); 6Mean value of m. temporalis, m. splenius, m. trapezius, distal dorsal middle finger, three tests on each place, both left and right side; 7Mean value heat and cold pain thresholds for frontal and thenar region, three tests on each side; Mann–Whitney U-test: (*)P = 0.05, *P < 0.05, **P < 0.01, ***P < 0.001.
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Preictal migraineurs had shorter latency to sleep onset than interictal migraineurs (2.0 vs 10.3 min, P < 0.01). Thermal pain thresholds were lower in interictal migraine compared to controls (P < 0.04). Only five sleep TTH patients were available. However, also non-sleep TTH (n = 15) had less fast arousals than sleep TTH patients (P < 0.05). Discussion
The major findings of the present study are (i) Patients with TTH report more insomnia than migraine patients; (ii) Patients with TTH and migraine report lower sleep quality and more insomnia, tiredness, and autonomic symptoms than controls; and (iii) In PSG, NSM and TTH patients had more slow-wave (N3) sleep than controls, that is, better sleep quality, which seemingly stood in contrast to the fact that they also reported more frequent daytime tiredness and tended to have reduced pain thresholds. We hypothesize that the latter findings are explained by a relative sleep deficit caused by a higher need of sleep in TTH and NSM patients. Subjective and objective sleep quality in controls and headache patients
Increased symptoms of anxiety, insomnia, and subjective tiredness among migraineurs and TTH patients have also been found by others (1, 22). Compared to controls, the reduced subjective sleep quality in headache patients was most striking. PSG sleep parameters differed, and although this difference was less striking, it seemed paradoxical compared to controls. Mean total sleep time in diaries did not differ between
The headache-sleep study Table 4 Comparison and interpretation of important symptoms and objective findings for the TTH, NSM, and SM patients compared to controls Group Sleep migraineurs Non-sleep migraineurs Tension-type headache
Summary of findings
Interpretation
Number of awakenings ↑, amount of superficial sleep (↑), but not increased daytime tiredness or sleepiness Slow-wave sleep ↑, fast arousals ↓, increased frequency of daytime tiredness, and reduced pain thresholds Slow-wave sleep ↑, increased frequency of daytime tiredness and tendency to reduced pressure pain thresholds
the groups (Table 2). It has been shown that a history of chronic insomnia does not predict poor EEG sleep (23). However, increased slow-wave sleep, as found in the present study among TTH and NSM patients, is one factor that usually indicates better sleep quality (24). Reduced amounts of fast arousals and increased slow-wave activity have also been found the night after experimental sleep deprivation (25) and are in line with what we found in TTH and NSM patients. After foregoing sleep deprivation, a ‘hypoarousal state’ with reduced fast arousals, increased slow-wave sleep, and increased daytime tiredness can be regarded as normal. However, in the present study, sleep diaries revealed normal average total sleep times before the PSG. Hence, the NSM and TTH patients seem to have a hypo-arousal state possibly related to a relative sleep deprivation caused by increased need for sleep. This hypothesis is consistent with the notion that EEG among migraineurs is found to be either normal or have subtle findings that may reflect drowsiness (26). Furthermore, among migraineurs, the sleepiness was even more increased in the preictal phase as mean sleep onset latency was reduced compared to interictal phase. Increased objective sleepiness in the preictal phase is consistent with subjective symptoms of drowsiness (27) and with objective EEG findings of slow activity preictally (28). However, our PSG findings differ from Karthik et al. (29) who demonstrated longer latency to sleep onset and less NREM sleep among migraineurs. Methodological differences such as patient selection might explain divergent results. SM patients differed from NSM and TTH patients by having reduced sleep quality in PSG (more awakenings than controls and less slowwave sleep than TTH and NSM). Hence, SM was the only group with an ‘objective parallel’ to their reported sleep disturbance. Lower index of slow EEG bursts in NREM and high-frequency EEG arousals during REM sleep have previously been found among interictal SM patients (30). These findings have been interpreted as hypofunction of the arousal system (30). In the present study,
Reduced sleep quality, preserved arousal system, or hyperarousal? Increased sleep need, recovery sleep, increased sleep quality, hypo-arousal? Increased sleep need, recovery sleep, increased sleep quality, hypo-arousal?
signs of hypo-arousability were prominent among the NSM, but not among the SM patients. The relatively few sleep TTH patients did probably not have a significant effect on the main results, but a post hoc comparison showed that also nonsleep TTH patients had less fast arousals than sleep TTH patients. Accordingly, we hypothesize that the hypo-arousability observed among the NSM and TTH patients (mainly non-sleep TTH) may be related to a relative sleep deprivation and that these patients also may need more sleep than healthy controls (Table 4). Pain and sleep
We found decreased thermal pain thresholds in the NSM and reduced pressure pain thresholds in chronic TTH patients in concert with other studies (7, 31). Reduced pain thresholds have also been found among healthy volunteers after sleep deprivation (5). Migraineurs with head allodynia during attack also report more sleep disturbances than non-allodynic migraineurs when compared to controls (32). In the present study, PSG and pain threshold findings among NSM and TTH (mostly non-sleep TTH) patients are in principle similar. These findings, together with normal average sleep times, are also consistent with a relative sleep deprivation (5). Preictal reduction in sleep onset latency in the present study and preictal heat pain threshold reduction in a previous study (8) are also compatible with sleep deprivation as a headache trigger. However, among SM patients in the present study, disturbed sleep in PSG, probably disposing for sleep deprivation, was not accompanied by reduced daytime vigilance or reduction in pain thresholds. Hence, we hypothesize that arousability is constitutionally different in our groups: decreased in NSM (and TTH) and conserved in SM patients. Arousability can in fact be associated with autonomic activity and possibly explains pain threshold changes. Indeed, arousability has been linked to hypertension (33) while high blood pressure also seems to be associated with hypo-algesia (34). 51
Engstrøm et al. Headache onset time
The NSM and TTH patients had quite corresponding results, possibly because the majority of our TTH patients were non-sleep TTH. This interesting finding suggests that sleep and attackprecipitating mechanisms are similar across different headache diagnoses. Hence, the increased combined load of affective and sleep-related symptoms might be the main etiological factor for headache. If so, the individual headache onset time may only depend on which ‘drop’ that made the flood. Increased susceptibility to daytime load and subsequently increased need for sleep are probably characteristic for headaches that tend to start during daytime, while increased susceptibility to sleep disturbances probably is characteristic when headache begins during sleep. However, in the present study compared to migraineurs the TTH group had a higher headache frequency and, not surprisingly, headache was accompanied by increased insomnia symptoms. The SM group had no signs indicating sleep deprivation per se according to the sleep diary, PSG, daytime tiredness score, and pain thresholds. However, disturbed sleep could increase the risk for sleep deprivation (35), and symptoms related to sleep, anxiety, and autonomic activity among SM did not differ from other headache groups. The latter signs might be part of what make TTH and NSM patients wearier and increase the sleep need (Fig. 3). Hence, we hypothesize that SM patients have a more robust arousal system than NSM and TTH. SM patients may even be in a hyperarousal state. We could not detect differences in sleep disturbing parameters (AHI and PLM indexes) between SM patients and NSM or controls. A susceptibility to clinically nonsignificant sleep disturbances might be a disadvantage of a robust arousal system. This notion is in concert with the observed increase of SM by age as sleep gets lighter with increasing age (36). One might speculate that the difference in arousability between the groups with attack onset during awake hours and during sleep is related to the periaqueductal gray (PAG) matter as ‘hyperarousal’ and ‘hypoarousal’ have been related to ventrolateral and lateral/dorsal PAG regions, respectively (37). Strengths and limitations
The blinded and controlled cross-sectional study design increases the probability for valid results. Furthermore, the participants were mainly recruited by advertising in local newspapers, in 52
Figure 3. Hypothesized different nervous system responses to increased daily life strain.
contrast to a hospital-based migraine population which may include more severe and long-standing cases. On the other hand, the selection of headache patients responding to a newspaper advertisement may not be fully representative for the whole headache population. It is evidently impossible to recruit a completely unbiased patient population. However, as most migraine patients had been prescribed triptans for their attacks and because headache history and headache intensity were comparable to a previous hospital-based population (38), our study groups were probably fairly representative for a patient group encountered in a clinical setting. A study design with repeated PSGs may be more powerful for the detection of phase-related differences. Individualized matched controls for age and sex would have been preferable rather than a comparable control group. A slight underestimation of sleep problems is expected in our study because patients with known and diagnosed previous sleep disorders were excluded; however, this exclusion is a strength regarding the major aims of the study. This study was exploratory, and we did not adjust for multiple comparisons because we did not want to increase type II failures on the cost of reducing type I failures (39). The possibility of both type I and type II errors is acknowledged. Independent replication of our results is accordingly needed. Conclusions
We have unified and compared data reported in three papers (9–11), we conclude that all our headache groups reported more anxiety and sleep-related symptoms than controls. Even though average total sleep times in TTH (mainly non-sleep TTH) and interictal NSM patients were normal, they had objective and subjective signs consistent with a hypo-arousal state consistent
The headache-sleep study with foregoing sleep deprivation. SM patients had findings in PSG consistent with disturbed and lighter sleep, but they paradoxically did not report more frequent daytime tiredness. The SM patients seemed to have a more robust arousability, possibly making them more susceptible for sleep disturbing factors like hypopneas or PLMs within the normal range. The combined results from these studies suggest that there are subgroups within both the tension-type headache and the migraine group in which sleep patterns and attack-precipitating mechanisms are different. However, the TTH and NSM subgroups had very similar sleep and pain thresholds suggesting the presence of common attack-initiating mechanisms across headache disorder boundaries. Acknowledgments We thank Grethe Helde, Marit Stjern, and Gøril Bruvik Gravdahl for practical assistance. This study was supported by grant from Department of Neuroscience; Norwegian University of Science and Technology, and Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU). Trondheim, Norway.
Conflict of interest None.
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