**2. Pathophysiology**

Headaches and sleep disorders share similar neurochemistry and neuroanatomy. The ascending reticular activating system (ARAS) is a multi-neuronal polysynaptic system, which promotes wakefulness. The ARAS has two main ascending activating pathways: first one is located in the brainstem, and projects to the thalamus, and the second is a thalamocortical pathway with its glutamate-containing neurons. The second pathway is a mono-aminergic with several brainstem nuclei including periaqueductal gray (dopamine), locus coeruleus (noradrenaline), dorsal raphe nuclei (serotonin), and tuberomammillary (histamine). These nuclei containing neurochemical neurons project through the hypothalamus to the basal forebrain (cholinergic system) and to the cerebral cortex, to promote wakefulness. Finally, hypocretin-containing neurons (excitatory neuropeptide) that via lateral hypothalamus project to the cerebral cortex to awake it [4].

Sleep is divided into rapid eye movement (REM) sleep and non-REM (NREM) sleep. Non-REM sleep is subdivided in three sleep stages: stage N1, stage N2, and stage N3. Stage N1 is a bridge between wakefulness and sleep (light sleep stage) where individual can be easily aroused. As sleep deepens, it moves into stage N2 defined by the presence of spindles and K-complex on the EEG, and Stage N3 a deep sleep stage where people are hard to arouse. The neurons that induce non-REM sleep are located in the anterior hypothalamus and inhibit the ARAS and the main neurochemicals are serotonin and gamma-aminobutyric acid (GABA). REM-sleep is defined by electroencephalographic features of wakefulness, loss of muscle tone (atonia), and rapid eye movements. The neurons that induce REM sleep are located in the upper pons and the main neurochemical is acetylcholine [4].

The rhythmicity of awake and sleep stages, also known as circadian rhythm, is regulated by an internal biological "clock" located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. Neurons of the SCN are capable of almost constant self-sustained cycle. This rhythmicity is accomplished through a precisely timed and highly regulated negative feedback between specific gene expressions and their resulting proteins. Light exposure, social activities, physical activity, and melatonin (a pineal gland hormone) assist this synchronized, also called entrained, internal clock. The wake and sleep time is also controlled by the homeostatic drive that results from extracellular accumulation of adenosine (ATP byproduct) that increases during wakefulness and the longer is the sleep deprivation period - the more intense is the drive to sleep. The dynamic balance between the circadian and homeostatic drive promotes either wakefulness or sleep [4].

Migraine is associated with the inappropriate central activation of painful neuronal pathways. These pathways involve brainstem, thalamus, hypothalamus, and cortex—the same structures which are involved in the regulation of wakefulness and sleep, [5–7] especially locus coeruleus, dorsal raphe nuclei, periaqueductal gray, and hypothalamus. Brainstem nuclei, locus coeruleus and dorsal raphe nucleus are implicated in the nociceptive control and modification of the cerebral blood flow [5–8]. Periaqueductal gray stimulation with electrodes may trigger migraine-like headache [9]. DBP of the PAG for other painful disorders was associated with induction of migraine in prior nonmigraines [10] and increase in iron content in the PAG of migraine patients [11, 12]. In migraine, there is an increment in the regional cerebral blood flow (rCBF) of the dorsal PAG and raphe nuclei [13]. Hypothalamus is implicated in the pathogenesis of migraine and cluster headache. The suprachiasmatic nucleus is localized in the hypothalamus, which connects with the periaqueductal gray, spinal nociceptive, and ARAS, all of which are implicated in mechanisms of pain and headache. Hypothalamus plays a

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*Comorbid Sleep Disorders and Headache Disorders DOI: http://dx.doi.org/10.5772/intechopen.93358*

**3. Clinical diagnosis**

hypothallus is implicated in the genesis of CH [15, 16].

likely to diagnose parasomnias and narcolepsy.

**4.1 Primary headaches associated with sleep disorders**

**4. Headache types and sleep**

role in the early phase of migraine—premonitory phase, which precedes headache phase by up to 72 hours and presents with fatigue, yawning, food cravings, and is associated with an increase in the hypothalamic blood flow [14]. Hypothalamic activation during cluster headache (CH), increase in the hypothalamus gray matter, and DBS efficacy in treating the refractory CH, supports the theory that

The appropriate diagnosis of headaches and sleep disorders, relays on history, physical examination and corroborated by additional tests such as polysomnography, and at times mean sleep latency test (MSLT). Detailed history of headache characteristics is essential, since diagnosis of headache disorders relays solely on history, while the diagnosis of sleep disorders can be approximated by history, but often requires a sleep study for confirmation, for instance for the diagnosis of sleep apnea. Several questionnaires have been designed for the diagnosis of headache and sleep disorders. Headache questionnaire and headache diary may assist in assessment and quantification of the headache's frequency, severity, associated features, and response to the specific therapy. Sleep questionnaire may also assist in determination of the levels of drowsiness as in the Epworth sleepiness scale, which attempts to assess the levels of drowsiness in different scenarios of daily life, with score of 10 or higher being associated with the significant impairment in the activities of daily leaving. Other questionnaires as STOP-BANG are more specific for determination of the probability of having the sleep apnea. Other questionnaires may determine the severity of the restless leg syndrome. Polysomnography is the gold standard for the diagnosis of sleep disorders, especially obstructive sleep apnea, periodic leg movement of the sleep, and is less

Migraine with and without aura. Migraine is defined as uni- or bilateral, moderate to severe headache associated with photophobia, phonophobia, and nausea and/ or vomiting, and aggravated by activity. Migraine is reciprocally intertwined with sleep patterns. Too much or too little sleep at night or irregular sleeping pattern (circadian rhythm disorders or sleep fragmentation) are all common migraine triggers. Meanwhile, sleep may have a curative effect on the migraine headaches—the so-called "healing naps" (2). Nearly 90% of episodic migraineurs who complain of poor sleep quality and poor night sleep, have more severe migraine and increased daily burden [17]. Sleep hygiene could be a trigger or relieving factor for migraine chronicity, depending on whether it is poor or good, respectively [18]. Poor sleep quality and/or duration is a trigger for migraine [19] and causes increase in migraine frequency [20]. Similarly, Korean study showed increase in frequency of migraine in patients with poor sleep [21]. Migraine is related to several sleep disorders, such as insomnia, OSA, parasomnias, sleep-related movement disorders, REM-sleep related disorders [22]. Half to two-thirds of migraineurs suffer from insomnia [23]—the most common sleep disorder, and migraineurs have a 3-fold increase in daytime sleepiness [24]. Insomnia is more common in patients with chronic

*Comorbid Sleep Disorders and Headache Disorders DOI: http://dx.doi.org/10.5772/intechopen.93358*

role in the early phase of migraine—premonitory phase, which precedes headache phase by up to 72 hours and presents with fatigue, yawning, food cravings, and is associated with an increase in the hypothalamic blood flow [14]. Hypothalamic activation during cluster headache (CH), increase in the hypothalamus gray matter, and DBS efficacy in treating the refractory CH, supports the theory that hypothallus is implicated in the genesis of CH [15, 16].
