Excessive daytime sleepiness in migraine patients
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《神经病学神经外科学杂志》
1 Hospital Israelita Albert Einstein, S?o Paulo, Brazil
2 Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Correspondence to:
Dr Mario Fernando Prieto Peres
Instituto Israelita de Ensino e Pesquisa–Albert Einstein, Av Albert Einstein 627/701, S?o Paulo SP, Brazil; marioperes@yahoo.com
Keywords: migraine; daytime sleepiness
Headache and sleep disorders are related in several ways. Sleep disorders occur in headache patients, headache is a common manifestation of sleep disorders, and secondary disorders may cause headache and sleep complaints. Excessive daytime sleepiness (EDS) or excessive somnolence is a common symptom, with a prevalence of 10–20% in the general population.1
EDS is a subjective feeling of a compelling need for sleep at unusual times and in abnormal environmental conditions. Sleep deprivation, sleep fragmentation, and hypoxia are believed to be the main mechanisms leading to EDS. EDS increases the risk of car accidents, causes health status and quality of life to deteriorate, and may increase mortality. EDS is associated with obstructive sleep apnoea syndrome, brain tumours, epilepsy, stroke, degenerative diseases, trauma, multiple sclerosis, and neuromuscular disorders.1 The prevalence, mechanisms, impact, diagnosis, and treatment of EDS have never been assessed in migraine patients.
We studied 200 consecutive patients with chronic or episodic migraine diagnosed according to the second edition of the International Headache Society diagnostic criteria for migraine2 from the Jefferson Headache Center, Philadelphia, USA. The Epworth sleepiness scale (ESS)3 was applied to all patients and correlated with the diagnosis of chronic/episodic migraine, age, sex, body mass index (BMI), and headache frequency. Questions on mental and physical fatigue, concentration, and memory problems were rated using a 1 to 5 scale. The local ethics committee approved the study. EDS was defined as an ESS score of 10 or more.
Statistical analysis was done using the 2 and Fisher exact tests for proportions, and Spearman and Pearson’s correlation tests. The level of significance was set at p<0.05.
Demographic data are given in table 1. Headache after dozing off was reported in 35% of all migraine patients (29% episodic, 40% chronic), and in 70% of patients with EDS. The chance of dozing off in a car was high in 1% of patients, moderate in 2%, and slight in 15%. The ESS correlated with mental fatigue, physical fatigue, concentration, and memory complaints (p<0.05), but did not correlate with BMI, age, or sex (NS). The mean (SD) ESS was 8.4 (4.3). An ESS score of 10 or more was present in 37% of all people with migraine, in 32.4% of those with episodic migraine, and in 39.8% of those with chronic migraine. A score of 15 or more was present in 10% of all migraine sufferers, in 15.3% of those with chronic migraine, and in 4.3% of those with episodic migraine (p<0.05; table 1).
Table 1 Demographic data and Epworth sleepiness scale in 200 patients with episodic and chronic migraine
Comment
EDS is increasingly recognised as a significant public health problem.1 It is common in migraine compared with the general population, with around a twofold increased prevalence in our migraineurs.
The risk of car accidents is assessed in other medical disorders based upon daytime sleepiness severity. Little attention has been paid to the risk of car accidents in migraine sufferers. EDS should be evaluated in this population because of the risk of accidents in those who report severe EDS.
EDS was correlated with fatigue in the migraine patients in our study. Fatigue has been reported in 85% of chronic migraine sufferers, and was found to be very common as a premonitory symptom in migraine.4 Understanding the causes of EDS in migraine may shed light on the mechanisms of fatigue in these patients
Dozing off was recognised as a headache trigger in 35% of patients and in 70% of patients with EDS. EDS may aggravate migraine, and diagnosing and treating it may lead to better outcomes.
Sleep loss or inadequate sleeping time is the most common cause of EDS in the general population. Primary sleep disorders—such as sleep disordered breathing, restless legs syndrome, and periodic leg movements in sleep—are prevalent, particularly among older people and may contribute to EDS. Other medical conditions, such as cardiovascular and pulmonary diseases, psychiatric illness, chronic pain syndromes, and several neurological and neurodegenerative disorders, can disrupt sleep and lead to EDS. Moreover, drugs including diuretics, antihypertensives, sympathomimetic agents, corticosteroids, sedative-hypnotics, analgesics, and certain antidepressants can cause EDS by interfering with sleep continuity or by having a direct sedating effect in the daytime.1
Can migraine lead to EDS, is EDS the primary condition leading to migraine, or are migraine and EDS determined by different causes? All three possibilities may occur. First, EDS may be an accompanying symptom in migraine, and an increased EDS may be a result of having migraine; the frequency of migraine may also affect EDS, as our chronic migraineurs scored higher. Second, EDS may precipitate migraine attacks—in our study dozing off was reported to be a headache trigger in 35% of migraine patients and in 70% of those with EDS. Third, depression could be related to both migraine and EDS, because it is comorbid with migraine and can cause EDS. A control group and the evaluation of depression and anxiety symptoms would help to clarify the exact relation between EDS and migraine.
We previously hypothesised a hypothalamic involvement in chronic migraine.5 The hypothalamus is potentially the mediator of EDS in migraine patients. Orexin, a recently described neuropeptide, is thought to play a role in the regulation of food intake, sleepiness, autonomic nervous system activity, and energy balance. Orexin containing cells are located in the lateral hypothalamus, with widespread projections to the entire neuroaxis. Input from the suprachiasmatic nucleus to orexin containing neurones may explain the occurrence of clock dependent alertness. Orexin cells drive monoaminergic activity across the sleep cycle and this is related to pain modulation. A recent study showed that injection of orexin A in the posterior hypothalamic area decreased the A and C fibre responses to dural electrical stimulation and decreased spontaneous activity, while orexin B had the opposite effect, supporting a role of orexins A and B in the nociceptive processing of meningeal input.6
No specific treatment is available for EDS in migraine, though possibly physical exercise may play a role. Polysomnography, the multiple sleep latency test, and the ESS are useful tests for evaluating EDS in migraine patients; however, their clinical relevance has yet to be determined.
References
Carskadon MA. Evaluation of excessive daytime sleepiness. Neurophysiol Clin 1993;23:91–100.
Headache Classification Subcommittee of the International Headache Society. In: The international classification of headache disorders. 2nd ed. Cephalalgia 2004;24 (suppl 1) :1–160.
Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540–5.
Giffin NJ, Ruggiero L, Lipton RB, et al. Premonitory symptoms in migraine: an electronic diary study. Neurology 2003;60:935–40.
Peres MF, Sanchez del Rio M, Seabra ML, et al. Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry 2001;71:747–51.
Bartsch T, Levy MJ, Knight YE, et al. Differential modulation of nociceptive dural input to Orexin A and B receptor activation in the posterior hypothalamic area. Pain 2004;109:367–78.(M F P Peres1,2, M A Stile)
2 Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Correspondence to:
Dr Mario Fernando Prieto Peres
Instituto Israelita de Ensino e Pesquisa–Albert Einstein, Av Albert Einstein 627/701, S?o Paulo SP, Brazil; marioperes@yahoo.com
Keywords: migraine; daytime sleepiness
Headache and sleep disorders are related in several ways. Sleep disorders occur in headache patients, headache is a common manifestation of sleep disorders, and secondary disorders may cause headache and sleep complaints. Excessive daytime sleepiness (EDS) or excessive somnolence is a common symptom, with a prevalence of 10–20% in the general population.1
EDS is a subjective feeling of a compelling need for sleep at unusual times and in abnormal environmental conditions. Sleep deprivation, sleep fragmentation, and hypoxia are believed to be the main mechanisms leading to EDS. EDS increases the risk of car accidents, causes health status and quality of life to deteriorate, and may increase mortality. EDS is associated with obstructive sleep apnoea syndrome, brain tumours, epilepsy, stroke, degenerative diseases, trauma, multiple sclerosis, and neuromuscular disorders.1 The prevalence, mechanisms, impact, diagnosis, and treatment of EDS have never been assessed in migraine patients.
We studied 200 consecutive patients with chronic or episodic migraine diagnosed according to the second edition of the International Headache Society diagnostic criteria for migraine2 from the Jefferson Headache Center, Philadelphia, USA. The Epworth sleepiness scale (ESS)3 was applied to all patients and correlated with the diagnosis of chronic/episodic migraine, age, sex, body mass index (BMI), and headache frequency. Questions on mental and physical fatigue, concentration, and memory problems were rated using a 1 to 5 scale. The local ethics committee approved the study. EDS was defined as an ESS score of 10 or more.
Statistical analysis was done using the 2 and Fisher exact tests for proportions, and Spearman and Pearson’s correlation tests. The level of significance was set at p<0.05.
Demographic data are given in table 1. Headache after dozing off was reported in 35% of all migraine patients (29% episodic, 40% chronic), and in 70% of patients with EDS. The chance of dozing off in a car was high in 1% of patients, moderate in 2%, and slight in 15%. The ESS correlated with mental fatigue, physical fatigue, concentration, and memory complaints (p<0.05), but did not correlate with BMI, age, or sex (NS). The mean (SD) ESS was 8.4 (4.3). An ESS score of 10 or more was present in 37% of all people with migraine, in 32.4% of those with episodic migraine, and in 39.8% of those with chronic migraine. A score of 15 or more was present in 10% of all migraine sufferers, in 15.3% of those with chronic migraine, and in 4.3% of those with episodic migraine (p<0.05; table 1).
Table 1 Demographic data and Epworth sleepiness scale in 200 patients with episodic and chronic migraine
Comment
EDS is increasingly recognised as a significant public health problem.1 It is common in migraine compared with the general population, with around a twofold increased prevalence in our migraineurs.
The risk of car accidents is assessed in other medical disorders based upon daytime sleepiness severity. Little attention has been paid to the risk of car accidents in migraine sufferers. EDS should be evaluated in this population because of the risk of accidents in those who report severe EDS.
EDS was correlated with fatigue in the migraine patients in our study. Fatigue has been reported in 85% of chronic migraine sufferers, and was found to be very common as a premonitory symptom in migraine.4 Understanding the causes of EDS in migraine may shed light on the mechanisms of fatigue in these patients
Dozing off was recognised as a headache trigger in 35% of patients and in 70% of patients with EDS. EDS may aggravate migraine, and diagnosing and treating it may lead to better outcomes.
Sleep loss or inadequate sleeping time is the most common cause of EDS in the general population. Primary sleep disorders—such as sleep disordered breathing, restless legs syndrome, and periodic leg movements in sleep—are prevalent, particularly among older people and may contribute to EDS. Other medical conditions, such as cardiovascular and pulmonary diseases, psychiatric illness, chronic pain syndromes, and several neurological and neurodegenerative disorders, can disrupt sleep and lead to EDS. Moreover, drugs including diuretics, antihypertensives, sympathomimetic agents, corticosteroids, sedative-hypnotics, analgesics, and certain antidepressants can cause EDS by interfering with sleep continuity or by having a direct sedating effect in the daytime.1
Can migraine lead to EDS, is EDS the primary condition leading to migraine, or are migraine and EDS determined by different causes? All three possibilities may occur. First, EDS may be an accompanying symptom in migraine, and an increased EDS may be a result of having migraine; the frequency of migraine may also affect EDS, as our chronic migraineurs scored higher. Second, EDS may precipitate migraine attacks—in our study dozing off was reported to be a headache trigger in 35% of migraine patients and in 70% of those with EDS. Third, depression could be related to both migraine and EDS, because it is comorbid with migraine and can cause EDS. A control group and the evaluation of depression and anxiety symptoms would help to clarify the exact relation between EDS and migraine.
We previously hypothesised a hypothalamic involvement in chronic migraine.5 The hypothalamus is potentially the mediator of EDS in migraine patients. Orexin, a recently described neuropeptide, is thought to play a role in the regulation of food intake, sleepiness, autonomic nervous system activity, and energy balance. Orexin containing cells are located in the lateral hypothalamus, with widespread projections to the entire neuroaxis. Input from the suprachiasmatic nucleus to orexin containing neurones may explain the occurrence of clock dependent alertness. Orexin cells drive monoaminergic activity across the sleep cycle and this is related to pain modulation. A recent study showed that injection of orexin A in the posterior hypothalamic area decreased the A and C fibre responses to dural electrical stimulation and decreased spontaneous activity, while orexin B had the opposite effect, supporting a role of orexins A and B in the nociceptive processing of meningeal input.6
No specific treatment is available for EDS in migraine, though possibly physical exercise may play a role. Polysomnography, the multiple sleep latency test, and the ESS are useful tests for evaluating EDS in migraine patients; however, their clinical relevance has yet to be determined.
References
Carskadon MA. Evaluation of excessive daytime sleepiness. Neurophysiol Clin 1993;23:91–100.
Headache Classification Subcommittee of the International Headache Society. In: The international classification of headache disorders. 2nd ed. Cephalalgia 2004;24 (suppl 1) :1–160.
Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540–5.
Giffin NJ, Ruggiero L, Lipton RB, et al. Premonitory symptoms in migraine: an electronic diary study. Neurology 2003;60:935–40.
Peres MF, Sanchez del Rio M, Seabra ML, et al. Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry 2001;71:747–51.
Bartsch T, Levy MJ, Knight YE, et al. Differential modulation of nociceptive dural input to Orexin A and B receptor activation in the posterior hypothalamic area. Pain 2004;109:367–78.(M F P Peres1,2, M A Stile)