Continuing Education Activity

Hypnic headaches are a primary headache disorder that presents in the elderly population and usually wakes people up from sleep. It is not very common, but because it could be misdiagnosed with giant cell arteritis, small and medium intracranial vasculitis, and other conditions, it is a critical disorder to be comfortable with its presentation. To avoid the misdiagnosis of hypnic headache, it must be promptly diagnosed and treated. This activity reviews the evaluation and treatment of hypnic headache and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Outline the typical presentation of a patient with hypnic headache.
• Describe the appropriate evaluation of hypnic headaches.
• Review the management options available for hypnic headache and what are the first-line options.
• Summarize the importance of knowing the updated criteria for the diagnosis of hypnic headache and improving care coordination and collaboration amongst the interprofessional team, which include the emergency department physician, primary care, or neurologist to enhance the delivery of care and improve outcomes for patients affected by hypnic headache.

Introduction

Headaches and chronic pain are amongst the leading cause of morbidity and years lived with disability in the world.[1] Headaches have been classified into various categories based on the International Classification of Headache Disorders criteria.[2] One such headache disorder is a hypnic headache.

Hypnic headache (HH) is a rare headache syndrome that occurs exclusively during sleep, usually at the same time at night. It also has been named before the clockwise headache or alarm clock headache. It is considered a primary headache, according to the international classification of headache disorders.[3]

HH is characterized by attacks of dull headaches that occur after the age of 50 years, at least 15 times per month, and come only during sleep with no associated autonomic symptoms. The attacks wake the patient during sleep and usually last more than 15 min after waking.[4]

Hypnic headache is a chronic disorder that can last for years, with no remission of headache, and 47 percent.[5]

Patients with migraine and hypertension are more likely to develop HH compared to others. Nearly all HH patients had some type of motor activity, such as getting out of bed and eating, drinking, showering, or reading when awakened by the headache attack. Still, they did not typically have the restlessness that is seen with cluster headache and trigeminal autonomic cephalalgias.[6]

Etiology

While the exact etiology is unknown, the apparent cyclicity and response to lithium suggest a pathophysiologic connection between cluster headache and hypothalamic dysfunction. 

Epidemiology

Hypnic headache is thought to be about 0.07% of all patients that come to the office with the chief complaint of headache. 

In the geriatric population, the ratio is 1.4%, according to an Italian study.[6]

However, in recent years HH is thought to be slightly more common than previous studies. It is estimated to be 0.3% to 0.6% in a French study.[7]

Pathophysiology

The timing of hypnic headache and the concomitant diabetes insipidus with a feeling of intense thirst that has been reported by few studies favor the involvement of hypothalamic structures. 

It has also been reported that sleep-disordered breathing has not been reported to be of high prevalence in patients diagnosed with HH. Continuous positive airway pressure and nocturnal oxygen supplementation did not improve symptoms in patients with HH. 

The onset of HH attacks are associated with rapid eye movement sleep, and this association could connect HH to arterial hypertension and low oxygenation that occur during REM sleep. 

The suprachiasmatic nucleus (SCN) remains a possible region involved in the origin of HH. As body ages, the cell numbers in the suprachiasmatic nucleus decrease significantly, which leads to a decrease in melatonin. The release of melatonin will be affected by the reduced SCN cells. The SCN projects to and receives afferents from brainstem periaqueductal gray, which means a pain modulating link is possible.[8][9]

History and Physical

Patients usually describe the headache as frequent recurrent headaches occurring only during sleep. They cause wakening and last for up to 4 hours. There are no characteristic associated symptoms and not attributed to other pathology. The formal criteria require according to ICHD-3 headaches that (1) develop only during sleep and cause awakening, (2) occur greater than or equal to 10 days per month for greater than or equal to 3 months, (3) last greater than or equal to 15 minutes for up to 4 hours after awakening, and (4) have no associated cranial autonomic symptoms or restlessness.[10] Additionally, the headache should not be accounted for by another ICHD-3 diagnosis.

Other characteristic features of the HH include [11]:

• Timing- Headache usually occurs exclusively with sleep with circadian rhythmicity.[12]
• Age- While it is characterized as a disease of the elderly (>50 years old), it has been reported in the young patient population as well.
• Gender- The disorder appears to affect both genders equally.
• Duration- These headaches are usually short-lasting (30 to 60 min) but can last up to 3 hours.
• Intensity- Usually moderate to severe in intensity with a small percentage of people reporting mild headaches.
• Character- Most commonly reported character is dull; however, it can be throbbing or pulsating as well.
• Location- Mostly bilateral and diffuse
• Associated features- These headaches are rarely associated with migrainous (nausea/vomiting or photophobia/phonophobia) or autonomic (lacrimation/conjunctival injection features).

Evaluation

Evaluation of patients with nocturnal headaches must include ruling out conditions like cerebral tumors, giant cell arteritis, obstructive sleep apnea (OSA), and other sleeping disorders.[13]

MRI brain with/without contrast is needed for patients to rule out any structural abnormality like tumors, etc. Overnight polysomnography (sleep) study is necessary to rule out OSA and other sleeping disorders. Once any organic cause of the headache is ruled out, the diagnosis is mostly clinical based on the ICHD-3 diagnostic criteria. MRI brain may also show grey matter volume reduction in the hypothalamus.

Treatment / Management

Treatment and management of headache disorders is a challenging task and requires a thorough evaluation.[14] While there is a lack of good quality clinical data for the management of hypnic headache, the following medications have shown benefit in the management of hypnic headaches.

• Lithium - Raskin et al. published the first reports on the effectiveness of lithium for the treatment of HH. Several other studies have been published since then, corroborating their findings. Effective dose- 150 to 600 mg/day in single or divided doses to a serum level of 0.5 to 1.0 mmol/L.

• Indomethacin has shown positive results with the management of HH.[15] It is particularly beneficial in patients with hemicranial hypnic headaches or patients with associated autonomic features. The usual dose for treatment is 25 to 150 mg at bedtime. The physician should be cautious of the side effects while prescribing the medication in the elderly population.[16]
• Caffeine - 40 to 60 mg of caffeine has shown good results in the treatment of HH. It is also very well tolerated in the elderly population and surprisingly does not interfere with sleep. This is often used as a first-line treatment of these headaches.
• Other medications felt to be ineffective but with conflicting evidence include tricyclic antidepressants, flunarizine, beta-blockers, verapamil, NSAIDs, prednisolone, other anticonvulsants, acetazolamide, melatonin, benzodiazepines, pizotifen, and topiramate.[17]
• There have been case reports suggesting the efficacy of onabotulinum toxin and occipital nerve stimulation.[18][19][20] Physicians must be cautious about the possible complications of such invasive therapies.[21][22]

Differential Diagnosis

Differential diagnosis of hypnic headache may include other headache disorders that may have a predilection to occur during sleep. These other headache disorders may include migraine, cluster headaches, cervicogenic headache, SUNCT.[23][24][25] 

Prognosis

It has been reported that around 17% of patients achieve spontaneous remission over the course of times; however, most patients continue to suffer from it chronically. Another study has reported that 40% of patients achieve freedom from these headaches with treatment. In another published study, 53% of patients enter an episodic course following treatment.[10]

Complications

There are no reported long term neurologic sequelae to this condition.[26] 

Deterrence and Patient Education

As the pathology and exact etiology of these headaches are still unclear, the prevention of these headaches is still not possible. However, prophylactic strategies have demonstrated good outcomes in suppressing the headache attacks.

Enhancing Healthcare Team Outcomes

The diagnosis of hypnic headache is essential as there are many differential diagnoses that are very similar. History taking is the most critical step in the evaluation of these patients and also proper work up to rule out all secondary causes of such headaches like cerebral tumors, etc.

All members of the healthcare team should be familiar with this condition as it is not very common, but they do occur in the real world and must be well managed.