**5. Treatment**

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

and somnambulism in children [35].

index of greater than 25 kg/m2 [36].

during REM sleep [37].

migraine (with at least 15 headaches per month) than in patients with episodic migraine [25]. Migraine is closely linked to insomnia as they trigger or aggravate each other [26, 27]. CBT for insomnia improves headache frequency [28]. One third of patients with the refractory chronic daily headache is diagnosed with OSA [29]. There is strong comorbidity between migraine and OSA [2] and patient with migraine who are compliant with CPAP have lower incidence of headaches. The use of opioids for management of headaches is not recommended, but they are still often used, and are also associated with central sleep apnea [30] with increase in nocturnal hypoxemia [31]. Patient with more nocturnal migraines are usually older, have longer history of migraine and shorter sleep time, probably related to more sleep fragmentation often seen in older individuals [32]. There is also connection between migraine and RLS with an increase in frequency of RLS in migraines, and also RLS is more severe in patients with migraine [33], REM sleep behavior disorder (RBD) is more frequent in migraine patients [34] and these patients have severe headache-related disability and insomnia. Migraines is also associated with bruxism

Cluster headaches: are severe to very severe unilateral headaches, periorbital and temporal in distribution, lasting between 30 and 180 min, frequency of 1–8 headaches per day, and associated with conjunctival injection (red eye), increased lacrimation, rhinorrhea, and restlessness. Circadian and circannual periodicity is a hallmark of cluster headache. Two thirds of headaches occur at night between 9 PM and 10 AM. Cluster headaches are linked to REM sleep and to sleeping late in the morning—which has more REM sleep. The fact that individuals with cluster headaches have lucid recall of dreams 2 hours into sleep support the REM sleep association with CH. Patient with cluster headaches have a high incidence of OSA. A study showed over 8-fold increased risk for OSA in patients with cluster headache, and that risk increases further up to 24-fold in patients with an elevated body mass

Paroxysmal hemicrania (PH) is unilateral headache, side-locked (occurring on the same side), short-lasting, average duration of 30 minutes, occurring multiple times a day (up to 40 attacks a day), associated with autonomic features (conjunctival injection, lacrimation, rhinorrhea, ptosis, etc.) which primarily affects women. PH often occurs at night and is associated with REM sleep and occurs only

Hypnic headaches (HH) mainly affects elderly male patients, and presents with

Exploding head syndrome (EHS) was originally classified as a sleep disorder, which occurs during transition from wakefulness to sleep. Patients report hearing extremely loud or explosive noise, which is nonpainful, but is often associated with significant apprehension [37]. Recently, EHS was reported as an aura of migraine with brainstem aura while patient was fully awake [38]. Previously, EHS was

Tension-type headache is the most common type of headaches, which are known

as "featureless" headache, in contradistinction to migraine TTH are not usually associated with photophobia, phonophobia, or nausea. Insomnia often triggers or aggravates TTH, whereas sleep may relieve them [40]. Insufficient sleep or oversleeping may trigger TTH [41, 42]. Headaches, sleep disorders and depression may share common brain mechanisms, e.g. dysregulation of serotonin, melatonin and hypothalamic dysfunction and management of sleep disorders and depression is

mild to moderate bilateral headache, which awake patients from sleep, usually between 1 and 3 AM. It was believed to be related REM sleep, but recent studies

revealed that its occurrence is more common during NREM sleep [37].

reported as an aura of other type of migraine [39].

essential for the adequate control of the TTH.

**30**

The treatment is mainly targeted to relieve pain and associated features of headache. In case of migraine, the treatment has undergone major advances with the development of new specific anti-migraine therapies and more treatments are in development. If not a migraine- specific medication, treatment should be selected based on patient comorbidities, in order to address more than one problem at the same time. Medication should be initiated at the lowest dose with gradual increase of the dose to an effective range, while monitoring the response and potential adverse effects. Treatment, if well tolerated, should be continued for at least 2–3 months, with re-evaluation after that.

Migraine treatment algorithm is mainly divided into pharmacological interventions and nonpharmacological interventions. Among the pharmacological interventions the paradigm of treatment is based on preventative and acute/rescue therapy. Options included on the preventative armamentarium are oral antihypertensive (beta blockers, calcium blockers, ACEI/ARB), anti-depressants (SNRI/TCA), anticonvulsants (valproate, topiramate), Botox injections, CGRP mAB. Options for the acute treatment of migraine include triptans, Dihydroergotamine, Ergotamine, Neuroleptics, NSAIDs, and newer categories of recently FDA-approved gepants (ubrogepants) and ditans (lasmiditan). Among nonpharmacological interventions there are psychological interventions, including cognitive behavioral therapy (CBT), relaxation therapy and biofeedback. Neuromodulation including transcranial magnetic stimulation (TMS), Cefaly device, noninvasive vagus nerve stimulator GammaCore, remote electrical neuromodulation (REM), and acupuncture. Lifestyle modifications, including regular sleep and healthy diet, good hydration, management of triggers and stress management and use of supplements/vitamins, such as magnesium oxide and vitamin B2 (riboflavin) [46].

Acute treatment for cluster headache is mainly based on high flow oxygen and fast acting triptans, such as Sumatriptan and Zolmitriptan, available in injectable form and/or nasal spray. Inhalation of 100% oxygen by nonrebreather mask at a rate of 12–15 L/m for 10–15 minutes is used as a first line therapy. Acute therapy for cluster headaches requires fast acting routes of administration with subcutaneous triptans as

the most effective, followed by nasal and then oral formulations. Neuromodulation with GammaCore—a noninvasive vagus nerve stimulator, which was approved for both acute and preventive treatment of cluster headaches can be used safely multiple times per day, alongside with high flow oxygen. Other approaches for acute symptomatic management include occipital nerve blocks with local anesthetics and/or steroids, sphenopalatine ganglion block, intranasal 4% lidocaine spray or oral steroid taper as a transitional approach. As for prevention of cluster headaches, the drug of choice is verapamil with a total daily maintenance dose between 480–720 mg divided in 3 daily doses with immediate release formulation generally preferred. Lengthening of the PR interval is a feared adverse effect of Verapamil, with doses mainly above 240 mg a day, therefore ECG monitoring is recommended initiation of the therapy, after each dose adjustment, and every 6 months thereafter while on the medication. Other preventive regimens for cluster headache includes topiramate, lithium, melatonin, baclofen and valproic acid [46].

Among the paroxysmal headaches such as paroxysmal hemicrania, SUNCT (Short-Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing), SUNA (Short-Lasting Unilateral Neuralgiform Headache Attacks with Autonomic Symptoms), response to indomethacin is crucial and even included in diagnostic criteria for paroxysmal hemicrania and hemicrania continua. For patients, who cannot tolerate indomethacin other medications have been proposed, including cyclooxygenase type 2 inhibitors, verapamil, and topiramate. For the prophylaxis of SUNCT and SUNA the first line treatment is lamotrigine, followed by topiramate or gabapentin [46–48].

Treatment alternatives for hypnic headache include caffeine, melatonin, clonazepam, acetazolamide, indomethacin sustained release and lithium carbonate.

Treatment for TTH include pharmacological and nonpharmacological approaches. Simple analgesics, such as aspirin or other NSAIDs, acetaminophen, may be effective if only for a short period of time or if used infrequently. Preventive alternatives for TTH include tricyclic antidepressants (Amitriptyline) or SSRI's. Some patients respond to nonpharmacological approaches, such as massage, meditation, and biofeedback.

Continuous positive airway pressure (CPAP) is the mainstay of treatment for sleep apnea syndrome-related headaches, which appears to improve headache frequency and intensity [46–48].

**33**

**Author details**

Lourdes Benes Lima<sup>3</sup>

Elisa Marie Rossi2

Fabian Rossi1,2\*, Carlyn Rodriguez-Nazario1

2 UCF Medical School, Orlando, FL, USA

provided the original work is properly cited.

, Joshua Rossi2

and Nina Tsakadze1,2

4 Osceola Regional Medical Center, Kissimmee, Florida, USA

1 Orlando VA Medical Center, Orlando, Florida, USA

\*Address all correspondence to: fabian.rossi@va.gov

, Umesh Sharma1,2,

, Michelle Nunes4

, Aqsa Ullah4

,

, Mays Alani4

3 Director Parkinson Center, Orlando VA Medical Center, Orlando, Florida, USA

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

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

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

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

melatonin, baclofen and valproic acid [46].

gabapentin [46–48].

meditation, and biofeedback.

frequency and intensity [46–48].

the most effective, followed by nasal and then oral formulations. Neuromodulation with GammaCore—a noninvasive vagus nerve stimulator, which was approved for both acute and preventive treatment of cluster headaches can be used safely multiple times per day, alongside with high flow oxygen. Other approaches for acute symptomatic management include occipital nerve blocks with local anesthetics and/or steroids, sphenopalatine ganglion block, intranasal 4% lidocaine spray or oral steroid taper as a transitional approach. As for prevention of cluster headaches, the drug of choice is verapamil with a total daily maintenance dose between 480–720 mg divided in 3 daily doses with immediate release formulation generally preferred. Lengthening of the PR interval is a feared adverse effect of Verapamil, with doses mainly above 240 mg a day, therefore ECG monitoring is recommended initiation of the therapy, after each dose adjustment, and every 6 months thereafter while on the medication. Other preventive regimens for cluster headache includes topiramate, lithium,

Among the paroxysmal headaches such as paroxysmal hemicrania, SUNCT (Short-Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing), SUNA (Short-Lasting Unilateral Neuralgiform Headache Attacks with Autonomic Symptoms), response to indomethacin is crucial and even included in diagnostic criteria for paroxysmal hemicrania and hemicrania continua. For patients, who cannot tolerate indomethacin other medications have been proposed, including cyclooxygenase type 2 inhibitors, verapamil, and topiramate. For the prophylaxis of SUNCT and SUNA the first line treatment is lamotrigine, followed by topiramate or

Treatment alternatives for hypnic headache include caffeine, melatonin, clonazepam, acetazolamide, indomethacin sustained release and lithium carbonate. Treatment for TTH include pharmacological and nonpharmacological approaches. Simple analgesics, such as aspirin or other NSAIDs, acetaminophen, may be effective if only for a short period of time or if used infrequently. Preventive alternatives for TTH include tricyclic antidepressants (Amitriptyline) or SSRI's. Some patients respond to nonpharmacological approaches, such as massage,

Continuous positive airway pressure (CPAP) is the mainstay of treatment for sleep apnea syndrome-related headaches, which appears to improve headache

**32**
