Do nocturnal headaches matter? A prospective diary study on subjective sleep parameters in snorers and their bed partners

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1 Original Article Do nocturnal headaches matter? A prospective diary study on subjective sleep parameters in snorers and their bed partners Cephalalgia 2014, Vol. 34(7) ! International Headache Society 2013 Reprints and permissions: sagepub.co.uk/journalspermissions.nav DOI: / cep.sagepub.com Stefan Seidel 1, Sophie Frantal 2, Sabine Salhofer-Polanyi 1, Doris Lieba-Samal 1, Josef Zeitlhofer 1 and Christian Wöber 1 Abstract Background: The objective of this study was to assess the influence of nocturnal headaches (NH) on subjective sleep parameters prospectively in habitual snorers and their bed partners. Methods: We recruited habitual snorers and their bed partners via newspaper articles. The participants completed a semistructured interview, filled in questionnaires about quality of sleep (PSQI), daytime sleepiness (ESS), depression (SDS) and anxiety (SAS) and they kept a 90-day headache and sleep diary. Results: Seventy-six snorers (25 female) and 41 bed partners (31 female) completed the study recording a total of 6690 and 3497 diary days, respectively. NH were recorded on 222 (3.3%) and 79 (2.2%) days in 32 (42%) snorers and 17 (41%) bed partners, respectively. Snorers with NH showed significantly higher PSQI (5 3 vs. 4 2, p ¼ 0.004), SAS (38 11 vs , p ¼ 0.011) and SDS scores (39 12 vs , p ¼ 0.048) than snorers without NH. For bed partners with NH we found a significant female predominance (sex ratio f:m ¼ 16:1 vs. 12:12, p ¼ 0.005) and significantly higher SAS scores (38 6 vs. 33 8, p ¼ 0.030) compared with bed partners without NH. The subjective quality of sleep in habitual snorers (p < 0.001) as well as their bed partners (p ¼ 0.017) was negatively influenced by NH, but not total sleep time. Discussion: NH occurred in around 40% of snorers and their bed partners at least once during the 90-day observation period. Our results confirmed a negative impact on the subjective quality of sleep in both groups. Keywords Quality of sleep, nocturnal headaches, habitual snorers, bed partners, diary study Date received: 16 August 2013; revised: 26 October 2013; accepted: 29 October 2013 Introduction Based on previous studies (1 3), we know that the prevalence of frequent nocturnal headaches (NH) (i.e. more than once per week) ranges around 8% in the general population (3). They are associated with various sleep disorders such as restless legs syndrome, sleep-disordered breathing and bruxism (1,3). Primary headaches, especially migraine, and sleep complaints or even sleep disorders are heavily intertwined (4,5). On the one hand migraine attacks tend to start during the early hours of the day, and on the other hand difficulties to initiate or maintain sleep as well as excessive daytime sleepiness are more common in migraineurs (6,7). In our recent prospective study on prevalence of morning headaches (MH), which largely comprised migraine and tension type headache, we showed that waking up due to pain and waking up too early significantly predicted MH in habitual snorers and their bed partners (8). The largest study on prevalence of NH to date lacked methodological accuracy because of its retrospective assessment of NH and associated parameters by the telephone respondents (3). Thus, it was not possible for the authors to differentiate between nocturnal headaches as a circumscribed nocturnal 1 Department of Neurology, Medical University of Vienna, Austria 2 Department of Medical Statistics, Medical University of Vienna, Austria Corresponding author: Stefan Seidel, Department of Neurology, Medical University of Vienna, Währinger Gürtel 18 20, A-1090 Vienna, Austria. Stefan.seidel@meduniwien.ac.at

2 534 Cephalalgia 34(7) phenomenon and NH as the predecessor of MH. Conversely, studies on MH in individuals with sleepdisordered breathing (9 11) failed to obtain comprehensive data on headaches preceding MH. So far, no other study has prospectively assessed the prevalence of NH and its role as a potential contributor to impaired quality of sleep in habitual snorers and/or their bed partners. As true nocturnal headaches like hypnic headache (12) or paroxysmal hemicranias (13) are indeed rarities, we hypothesised that the majority of NH is only a part of an NH-MH continuum rather than an isolated nocturnal phenomenon. Previous studies investigating (14,15) subjective sleep parameters in habitual snorers and their bed partners have exclusively relied on retrospective sleep assessment. Thus, their ability to detect factors associated with the quality of sleep was hampered by a recall bias. To improve this paucity of information, we performed a post-hoc analysis of sleep log data compiled during a study on MH in habitual snorers and their bed partners (8). The aims of this study were to (a) assess the prevalence of NH in habitual snorers and their bed partners and (b) analyze the influence of NH on pivotal subjective sleep parameters (i.e. total sleep time (TST) and quality of sleep) in both groups. Patients and methods Between January 2009 and May 2011 habitual snorers were recruited via newspaper articles either alone or together with the non-snoring bed partner for a prospective study on MH in this population (8). Snorers and bed partners had to be between 18 and 75 years old, and able to fill out the study questionnaires as well as headache and sleep diaries. Exclusion criteria for snorers and bed partners were shift work, regular intake of sleep promoting substances, deafness or regular use of earplugs during sleep, substance addiction, severe respiratory disorders, and other severe medical or psychiatric conditions. Habitual snoring was defined as snoring daily or nearly daily. The study protocol was approved by the ethics committee of the Medical University of Vienna and written informed consent was obtained from all study participants. At baseline all snorers and bed partners underwent a semistructured interview covering demographics, height, weight, general medical and psychiatric history, previous headache diagnoses and pre-study headache frequency. In addition, the participants had to complete the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Self-rating Depression Scale (SDS) and the Self-rating Anxiety Scale (SAS). The PSQI measures the quality and quantity of sleep in the 4 weeks preceding the investigation. It differentiates poor from good sleep by seven areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction over the last 4 weeks. Scoring of answers is based on a 0 to 3 Likert scale, whereby 3 reflects the negative extreme. A total score of 5 or more indicates a poor sleeper (16,17). The ESS is also a self-rating instrument to evaluate the tendency for dozing off during daytime. It consists of eight items concerning everyday situations. Reponses to each item are ranked from 0 to 3 according to the probability for dozing off during a task (0 ¼ never, 1 ¼ low probability, 2 ¼ moderate probability, 3 ¼ high probability). A score >10 indicates excessive daytime sleepiness. The SDS is a 20-item self-report questionnaire of the symptoms of depression. Subjects rate each item according to how they felt during the preceding 7 days. Item responses are ranked from 1 to 4. The sum of the 20 items produces a score ranging between 20 and 80, a cut-off value of >40 suggests clinically relevant depression. The SAS measures affective and somatic symptoms of an anxiety disorder. The structure of the SAS is like the one of the SDS. It also consists of 20 questions, which refer to the last 7 days. The result of the SAS is obtained by summing up the scores. A cut-off value of >40 suggests the presence of a clinically relevant anxiety disorder. In habitual snorers, a portable device (Stardust, Respironics/Philips Medcare/Habel Medizintechnik, Vienna, Austria) was used for monitoring blood oxygen saturation during sleep and recording number and extent of nocturnal apnoea/hypopnoea episodes and arterial oxygen desaturation during one night of the 90-day diary period. The apnoea/hypopnoea Index (AHI) was used for classifying the severity of OSAS. According to the American Academy of Sleep Medicine Task Force (18) an AHI of <5h 1,5 15 h 1, h 1 and >30 h 1 indicated no, mild moderate and severe OSAS. Snorers and bed partners received a 90-day diary including instructions on how to use it. Headaches and subjective sleep parameters were documented by snorers and their bed partners every morning after breakfast for the preceding 24 hours. Participants recorded whether they experienced morning headache, headache (a) during the previous day, (b) at bedtime, (c) during the night or (d) at the present morning. Diary questions regarding sleep comprised consumption of alcohol, coffee, tobacco or eating a meal before sleep, sleep latency, total sleep time (TST), reasons for sleep disturbances and quality of sleep rated as excellent,

3 Seidel et al. 535 good, average or poor. In addition, bed partners had to record, if their sleep was disturbed because of any of the following sleep behaviour disturbances in their partner (i.e. the snorer): loud snoring, long breathing pauses, twitching of the legs, episodes of confusion during the night, and other sleep behaviour disturbances based on free recall. Study participants were excluded from the study if they filled out the diary for less than 10 days. Statistical analyses Data are presented as total numbers and percentages. Continuous variables are given as mean standard deviation. Baseline demographics and baseline headache data are compared between snorers and their bed partners using t-tests, chi 2 -tests or fisher-exact tests. To find influence factors on TST, separately for snorers and bed partners, linear regression models for repeated measures data were performed. Those factors which showed statistically significant influence univariately and after correction for multiplicity according to Bonferroni were further analysed in a multivariate model. Possible influencing factors for either snorers or bed partners are shown in Table 1. Additionally, episodes of abnormal sleep behaviour of the snorers which were observed and subsequently checked in the diary by the bed partners (i.e. nocturnal episodes of difficulties breathing, loud snoring, twitching or confusion), were included as possible influence factors and, hence, only snorers with a participating bed partner were included in these analyses. To see possible influence factors on the quality of sleep (Table 1), ordinal logistic regression models for repeated measures data were used univariately and multivariately. The analyses were performed using SAS 9.2. All p values <0.05 were considered as statistically significant. Results One-hundred and sixty-five individuals fulfilled the inclusion criteria. Forty-two (26%) were excluded Table 1. Influencing factors for total sleep time and sleep quality used in the logistic regression models. Baseline and general data Sex Age BMI Employment status Menstrual period Psychiatric comorbidity Pre-existing depression Pre-existing anxiety disorder Subjective sleep parameters PSQI score Awakening during night because of going to the toilet difficulties breathing coughing/loud snoring feeling too cold feeling too warm bad dreams pain Other reasons for disturbed sleep Consumption before bed time Alcohol Coffee Headache Headache during the previous day Nocturnal headache Chronic pain Coffee/alcohol consumption Level of education Weekday Current symptoms of depression (SDS score) Current symptoms of anxiety (SAS score) Sleep latency >30 minutes Sleep quality Sleeping arrangement Snorer s nocturnal episodes of difficulties breathing loud snoring twitching nocturnal confusion Heavy meal Tobacco Headache at bedtime BMI: body mass index; SDS: Self-report Depression Scale; SAS: Self-report Anxiety Scale; PSQI: Pittsburgh Sleep Quality Index.

4 536 Cephalalgia 34(7) because they did not return the diary. Of 123 study participants who completed the study, six were excluded from the final analysis, because they documented less than 10 diary days. Demographic details of snorers and bed partners can be seen in Table 2. Snorers differed statistically significantly from bed partners with respect to age (p ¼ 0.006), gender (p < 0.001) and BMI (p ¼ 0.01, Table 2). Patient-reported physician headache diagnoses as assessed in the semistructured interview comprised migraine in six (8%), tension-type headache in eight (11%), another type of headache in two (3%) and no headache in 60 (79%) snorers. Among bed partners, seven (17%) gave migraine, seven (17%) tension-type headache, one (2%) another type of headache and 26 (63%) did not report a previous headache diagnosis. None of the snorers or bed partners gave a pre-study headache frequency of 15 days per month or more. Baseline characteristics of snorers and bed partners regarding their NH status can be seen in Table 3. Snorers with NH showed significantly higher PSQI scores (5 3 vs. 4 2, p ¼ 0.004) than snorers without NH. SAS (38 11 vs , p ¼ 0.011) and SDS scores (39 12 vs , p ¼ 0.048) were significantly higher in snorers with NH than in those without NH. Significantly more bed partners with NH than those without NH were female (f:m ¼ 16:1 vs. 12:12, p ¼ 0.005) and those with NH showed significantly higher SAS scores than those without NH (38 6 vs. 33 8, p ¼ 0.030) (Table 3). We correlated the baseline variables headache diagnosis and pre-study headache frequency with age, sex, body mass index, subjective sleep quality (PSQI), depression (SDS)- and anxiety (SAS) scores in snorers and bed partners and found a significant correlation between the headache diagnosis migraine and subjective sleep quality (i.e. if the headache diagnosis was migraine, snorers reported worse subjective sleep quality) (p ¼ 0.043) in snorers and between the prestudy headache frequency and subjective sleep quality (p ¼ 0.005) (i.e. the higher the headache frequency the worse the subjective sleep quality) in bed partners. Headaches and pain medication Based on the prospective diary data, we assessed the intake of simple analgesics, triptans and opioids because of headache including nocturnal, morning or diurnal headache. Twenty-five (33%) snorers and 23 (56%) bed partners took at least one dose of a pain-relieving medication during the observation period. Simple analgesics with acetylsalicylic acid and paracetamol most commonly used comprised the vast majority of painrelieving medication. Only one snorer took an opioid (three times during the 90-day observation period) and Table 2. Demographic data of snorers and bed partners. one bed partner took a triptan (twice during the 90-day observation period). The frequency of intake of headache medication during the 90-day observation period ranged between one and 13 doses in snorers and between one and 17 doses in bed partners. Nocturnal headaches Snorers (n ¼ 76) Bed partners (n ¼ 41) p Sex (f:m) 25:51 31:10 <0.001 a Age (mean SD) a BMI (kg m 1 ) (mean SD) a Level of education (n (%)) Compulsory school 20 (26) 12 (30) Professional school 19 (25) 10 (24) A-Levels 23 (30) 13 (32) University diploma 14 (18) 6 (15) 1.0 Employment status (n (%)) Trainee 9 (12) 4 (9) Blue collar worker 2 (5) White collar worker 56 (74) 31 (76) Retiree 9 (12) 4 (10) Unemployed 2 (3) 0.5 Marital status (n (%)) No relationship 2 (3) Relationship 69 (91) 41 (100) Divorced 3 (4) Widowed 2 (3) 0.6 f: female; m: male; BMI: Body Mass Index; SD: standard deviation. a p statistically significant. In total, we analysed 6690 days of 76 snorers (25 female) and 3497 days of 41 bed partners (31 female). NH were recorded on 222 (3%) and 79 (2%) days in 32 (42%) snorers and 17 (41%) bed partners, respectively. During the 90-day observation period they were recorded during 7 10 (range 1 54 nights) and 5 6 (range 1 26 nights) nights in snorers and bed partners, respectively. NH was preceded by headache at bedtime on 20 (9%) and 11 (14%) days in snorers and bed partners, respectively. In snorers NH was followed by MH on 127 (57%) and in bed partners on 30 (38%) days. NH was preceded by headache at bedtime and followed by MH on 45 (20%) and 25 (32%) days in snorers and bed partners, respectively. NH without any preceding or subsequent headaches occurred during 30 (14%) and 13 (16%) nights in snorers and bed partners, respectively (Figure 1).

5 Seidel et al. 537 Table 3. Baseline characteristics of snorers and bed partners according to their NH status. Snorers (n ¼ 76) Bed partners (n ¼ 41) With NH (n ¼ 32) Without NH (n ¼ 44) p With NH (n ¼ 17) Without NH (n ¼ 24) p Sex (f:m) 13:19 13: :1 12: a Age (mean SD) BMI (kg m 1 ) (mean SD) AHI N/A N/A PSQI (mean SD) a Sleep duration (mean SD) ESS (mean SD) SAS (mean SD) a a SDS (mean SD) a NH: nocturnal headaches; f: female; m: male; BMI: Body Mass Index; AHI: apnoea/hypopnoea index; PSQI: Pittsburgh Sleep Quality Index; ESS: Epworth Sleepiness Scale; SAS: Self-report Anxiety Scale; SDS: Self-report Depression Scale; N/A: not applicable; SD: standard deviation. a p statistically significant snorers bed partners NH -an isolated phenomenon? % of all nights with NH preceded by headache at bed time followed by MH preceded and followed isolated Figure 1. Columns indicate the percentage of nights with NH (from left to right) preceded by headache at bedtime, followed by MH, preceded and followed by headache and NH neither preceded nor followed (¼ isolated NH) in snorers (grey columns) and their bed partners (black columns). NH ¼ nocturnal headaches; MH ¼ morning headaches. Influencing factors on total sleep time (TST) in habitual snorers and bed partners Multivariate regression analyses showed that weekends (p ¼ 0.004) and breathing difficulties during sleep (p ¼ 0.04) significantly reduced TST in both snorers and bed partners. In snorers, TST was significantly reduced by twitching (p ¼ 0.02), a worse quality of sleep (ordinal 1 vs. 3 p ¼ 0.047, 1 vs. 4 p ¼ 0.01) and nocturnal confusion (p < 0.001). In bed partners, TST was significantly reduced by headache while going to sleep (p ¼ 0.01) and difficulties to maintain sleep (p ¼ 0.003) and a sleep latency > 30 minutes (p < 0.001).

6 538 Cephalalgia 34(7) Influencing factors on the subjective quality of sleep in habitual snorers and bed partners Quality of sleep was statistically significantly reduced by NH (p < resp. p ¼ ), difficulties to maintain sleep (p < resp. p ¼ 0.009), bad dreams (p < resp. p ¼ 0.008), a sleep latency > 30 minutes (both p < 0.001) and other reasons for disturbed sleep (p < resp. p < 0.001) for both snorers and bed partners in the multivariate model. Only feeling too hot during sleep (p ¼ 0.001) was an additional negative influencing factor for the snorers quality of sleep. For bed partners further negative influencing factors were the snoring noises of their partners (p < 0.001) and pain during sleep (p ¼ 0.02). Discussion This is the first study to prospectively assess the prevalence of NH and their influence on pivotal subjective sleep parameters in habitual snorers and their bed partners. Our key findings are (a) a 90-night prevalence of NH of approximately 40% in both groups and (b) a significant negative influence on the subjective quality of sleep by NH in both groups. Compared with the largest population-based study on NH (3), we found a considerably higher prevalence of NH in both of our groups. Our prospective approach may have been shielded more properly from recall bias and, contrary to Lucchesi et al. (3), we did not define a certain threshold of NH frequency. This enabled us to detect NH even if they occurred less frequently than once a week. Obese women aged between 50 and 59 years seem to be especially prone to developing NH (3). Our data do not support obesity as a risk factor. Still, we found significantly more women among bed partners with NH than among bed partners without NH. Such a finding has to be interpreted with caution. First, habitual snoring is a condition which is highly prevalent among men (19) and, consequently, most bed partners are female. They, on the other hand, suffer from migraine to a greater extent than men, and migraine attacks frequently occur during the early hours of the day (20). Previously, NH has been associated with sleep disorders like restless legs syndrome, bruxism, nightmares, but not with sleep apnoea syndrome (3). Regarding the latter, we did not find the AHI to be increased in snorers with NH either. Most recently, Lovati et al. even showed respiratory parameters in headache Clinical implications patients to be significantly better than in headachefree individuals (21). PSQI scores in snorers with NH were worse than in those without NH, and NH significantly worsened the quality of sleep in snorers and bed partners. Moreover, depression and/or anxiety scores were elevated in snorers and bed partners with NH. Hence, our results once again confirm the well-known hazardous triangle between (nocturnal) headaches, psychiatric comorbidities and disordered sleep (4,22,23). In detail, the prevalence of specific sleep disorders (e.g. RLS) is significantly higher in migraine patients than in patients with other headache disorders or the general population (24,25). Both sleep disorders and migraine are frequently associated with psychiatric comorbidities such as depression and anxiety disorders (26,27). Subjective and objective sleep parameters in migraineurs have shown to be worse than in healthy individuals (4,6). Some authors (4) argued that migraine itself with its frequent nocturnal onset debilitates sleep quality, and others even discerned changes of the sleep pattern in relationship to the predominant circadian distribution of migraine attacks, that is non-sleep-related and sleeprelated headaches (28). So, does NH come along by itself or is it either the sequel of headache at bedtime or the prequel of MH, or even sandwiched in between? To date, no other study has attempted to depict the temporal relationship between NH and other headaches. Our own data support the notion that about half of MH are present upon awakening or start shortly thereafter (8). The current analysis suggests that around three-quarters of NH precede MH or, in other words, that MH indeed starts out as NH during a significant number of nights. True NH as an isolated nocturnal phenomenon seemed to be the exception in our population. The interpretation of our results is limited by the lack of a phenomenological description of NH, because this was not the aim of the original study (8). We cannot present polysomnographic data of snorers and their bed partners. Our study is strengthened by its novel and prospective design, the use of a combined headache and sleep diary. In conclusion, we showed that NH in snorers and bed partners are indeed a relatively frequent phenomenon, but are commonly either preceded or followed by headache. They have a clearly negative influence on the subjective quality of sleep but not total sleep time.. Nocturnal headaches are a frequent phenomenon in habitual snorers and their bed partners.. They significantly worsen the subjective quality of sleep.. This type of headache most commonly occurs in conjunction with morning headaches.

7 Seidel et al. 539 Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest C.W. has received honoraria and travel funding from Allergan, AstraZeneca (Austria), Hermes Arzneimittel GmbH, Linde Gas (Austria), A. Menarini Pharma GmbH (Austria) and Pfizer (Austria). S.S. has received honoraria from UCB Pharma (Austria). The other authors declare that they have no conflicts of interest. References 1. Evans RW, Dodick DW and Schwedt TJ. The headaches that awaken us. Headache 2006; 46: Lucchesi LM, Hachul H, Yagihara F, et al. Does menopause influence nocturnal awakening with headache? Climacteric 2013; 16: Lucchesi LM, Speciali JG, Santos-Silva R, et al. Nocturnal awakening with headache and its relationship with sleep disorders in a population-based sample of adult inhabitants of Sao Paulo City, Brazil. Cephalalgia 2010; 30: Seidel S, Hartl T, Weber M, et al. Quality of sleep, fatigue and daytime sleepiness in migraine a controlled study. Cephalalgia 2009; 29: Kelman L and Rains JC. Headache and sleep: Examination of sleep patterns and complaints in a large clinical sample of migraineurs. Headache 2005; 45: Karthik N, Sinha S, Taly AB, et al. Alteration in polysomnographic profile in migraine without aura compared to healthy controls. Sleep Med 2013; 14: Barbanti P, Fabbrini G, Aurilia C, et al. A case-control study on excessive daytime sleepiness in episodic migraine. Cephalalgia 2007; 27: Seidel S, Frantal S, Oberhofer P, et al. Morning headaches in snorers and their bed partners: A prospective diary study. Cephalalgia 2012; 32: Thoman EB. Snoring, nightmares, and morning headaches in elderly women: A preliminary study. Biol Psychol 1997; 46: Go der R, Friege L, Fritzer G, et al. Morning headaches in patients with sleep disorders: A systematic polysomnographic study. Sleep Med 2003; 4: Aldrich MS and Chauncey JB. Are morning headaches part of obstructive sleep apnea syndrome? Arch Intern Med 1990; 150: De Simone R, Marano E, Ranieri A, et al. Hypnic headache: An update. Neurol Sci 2006; 27(Suppl 2): Goadsby PJ. Trigeminal autonomic cephalalgias. Continuum (Minneap Minn) 2012; 18: Blumen MB, Quera Salva MA, Vaugier I, et al. Is snoring intensity responsible for the sleep partner s poor quality of sleep? Sleep Breath 2012; 16: Blumen M, Quera Salva MA, d Ortho MP, et al. Effect of sleeping alone on sleep quality in female bed partners of snorers. Eur Respir J 2009; 34: Zeitlhofer J, Schmeiser-Rieder A, Tribl G, et al. Sleep and quality of life in the Austrian population. Acta Neurol Scand 2000; 102: Buysse DJ, Reynolds CF III, Monk TH, et al. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Res 1989; 28: Sleep-related breathing disorders in adults: Recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22: Sharief I, Silva GE, Goodwin JL, et al. Effect of sleep disordered breathing on the sleep of bed partners in the Sleep Heart Health Study. Sleep 2008; 31: Rains JC and Poceta JS. Headache and sleep disorders: Review and clinical implications for headache management. Headache 2006; 46: Lovati C, Zardoni M, D Amico D, et al. Possible relationships between headache-allodynia and nocturnal sleep breathing. Neurol Sci 2011; 32(Suppl 1): Rains JC, Poceta JS and Penzien DB. Sleep and headaches. Curr Neurol Neurosci Rep 2008; 8: Ohayon MM. Prevalence and risk factors of morning headaches in the general population. Arch Intern Med 2004; 164: Winter AC, Schu rks M, Berger K, et al. Migraine and restless legs syndrome in men. Cephalalgia 2013; 33: Schu rks M, Winter AC, Berger K, et al. Migraine and restless legs syndrome in women. Cephalalgia 2012; 32: Antonaci F, Nappi G, Galli F, et al. Migraine and psychiatric comorbidity: A review of clinical findings. J Headache Pain 2011; 12: Finan PH and Smith MT. The comorbidity of insomnia, chronic pain, and depression: Dopamine as a putative mechanism. Sleep Med Rev 2013; 17: Engstrom M, Hagen K, Bjork M, et al. Sleep quality, arousal and pain thresholds in migraineurs: A blinded controlled polysomnographic study. J Headache Pain 2013; 14: