Hypnic headache

What is hypnic headache

Hypnic headache is a rare disorder that occurs in patients over the age of 50 years in 92% (rarely in children).

Females are affected 65% of the time. The headache occurs only during sleep and awakens the sufferer at a consistent time (often 2 to 4 am). Nausea is infrequent and autonomic symptoms are uncommon.

The headache can be unilateral or bilateral, throbbing or nonthrobbing, and mild to severe in intensity.

The headache’s duration can range from 15 minutes to 10 hours, with most lasting less than 3 hours, and can occur frequently, as often as nightly, for many years. 

The best treatments are caffeine (one cup of strong caffeinated coffee or a 40- to 60-mg caffeine tablet before bedtime—insomnia is usually not reported in these patients), lithium carbonate (150 to 600 mg at bedtime), and indomethacin 25 to 50 mg tid and then tapering off after several weeks.

A number of other medications have been reported as effective in case reports.

Also known as alarm clock headache , hypnic headache is a term used to describe an uncommon headache syndrome characterized by its propensity to wake the person at the same time each night. Always occurring during sleep, hypnic headache is of short duration and rarely lasts more than 15 minutes after the patient is awakened by the pain.

Research suggests that hypnic headache occurs most commonly during rapid eye movement (REM) sleep and it has been suggested that hypothalamic dysregulation may be the pathologic mechanism that triggers this rare headache syndrome.

Hypnic headache occurs frequently, with a mean incidence of at least 15 attacks per month. The location of the headache pain varies, and the intensity of pain described as moderate with an aching character. Unlike cluster headache, which also occurs after sleep, patients with hypnic headache exhibit no autonomic signs or symptoms.

Hypnic headache is a disease of the late fifth and sixth decades, with a mean age of onset of 63 years, although cases in the pediatric and adolescent population have been reported. It occurs more commonly in females.

What are the Symptoms

Hypnic headache is associated with no obvious neurological or musculoskeletal disease. Specifically, there are no autonomic signs or symptoms as are often seen with cluster headache. Furthermore, no accompanying focal neurological signs or systemic symptoms occur as with cluster headache and migraine headache, although rarely nausea can occur. The age of onset of benign hypnic headache is generally in the late fifth or sixth decade of life.

Although no specific location is seen in hypnic headache, they are bilateral in 66% of patients. When the headaches are unilateral, they tend to occur on the same side night after night.

What is fascinating to the treating physician and frustrating to the patient is the fact that hypnic headache wakes the patient from a sound sleep at almost the same time each night.

Because the onset of hypnic headache occurs later in life, it must be considered a diagnosis of exclusion as with the other uncommon primary headache syndromes, for example, cough headache and thunderclap headache.

The clinician must assiduously search for other explanations for the patient’s headache symptomatology, including intracranial pathological conditions and systemic disease.

How is Hypnic headache diagnosed?

Magnetic resonance imaging (MRI) of the brain provides the best information regarding the cranial vault and its contents. MRI is highly accurate and helps identify abnormalities that may put the patient at risk for neurological disasters secondary to intracranial and brainstem pathological conditions, including tumors and demyelinating disease.

MRI helps identify bleeding associated with leaking intracranial aneurysms, which may mimic the symptoms of both types of hypnic headache. Magnetic resonance angiography (MRA) may be useful in identifying aneurysms responsible for the patient’s neurological symptoms. In patients who cannot undergo MRI, such as patients with pacemakers, computed tomography (CT) is a reasonable second choice.

Lumbar puncture should be performed if intracranial hemorrhage is suspected even if blood is not present on MRI or CT. Plain radiographs of the cervical spine also may be useful in the evaluation of Arnold-Chiari malformations and should be included in the evaluation of all patients with hypnic headache.

Screening laboratory tests consisting of complete blood cell count, erythrocyte sedimentation rate, and automated blood chemistry testing should be performed if the diagnosis of hypnic headache is in question. Intraocular pressure should be measured if glaucoma is suspected.

Differential Diagnosis

Hypnic headache is a clinical diagnosis supported by a combination of clinical history, physical examination, radiography, MRI, and MRA.

Pain syndromes that may mimic hypnic headache include the uncommon primary headaches benign exertional headache, ice pick headache, and sexual headache, although the unique same-time nocturnal occurrence should help the clinician easily identify the patient’s symptoms as hypnic headache.

The clinician must consider other types of headache that occur more frequently at night, including cluster headache and headaches associated with sleep apnea, nocturnal arterial hypertension, analgesic rebound, and increased intracranial pressure. Given that hypnic headache occurs in an older population, temporal arteritism must also be considered.

Nocturnal Headaches That May Be Confused With Hypnic Headache

Cluster headache

Headache associated with sleep apnea

Headache associated with nocturnal arterial hypertension

Headache associated with increased intracranial pressure

Analgesic rebound headache

Less commonly, hypnic headache may be confused with trigeminal neuralgia (involving the first division of the trigeminal nerve) or demyelinating disease. Trigeminal neuralgia involving the first division of the trigeminal nerve is uncommon and is characterized by trigger areas and tic-like movements.

Demyelinating disease is generally associated with other neurological findings, including optic neuritis and other motor and sensory abnormalities. The pain of chronic paroxysmal hemicrania and cluster headache is associated with redness and watering of the ipsilateral eye, nasal congestion, and rhinorrhea during the headache.

These findings are absent in hypnic headache. Migraine headache may or may not be associated with painless neurological findings known as aura, but patients almost always report some systemic symptoms, such as nausea or photophobia, not typically associated with hypnic headache.

Treatment

Indomethacin and lithium carbonate are the treatments of choice for hypnic headache, with indomethacin being slightly more effective for the unilateral form of the syndrome. Indomethacin at a starting dose of 25 mg daily for 2 days and titrating to 25 mg three times per day is a reasonable treatment approach. This dose may be carefully increased up to 150 mg per day. Indomethacin must be used carefully, if at all, in patients with peptic ulcer disease or impaired renal function.

Headache specialists have noted anecdotal reports of a positive response to cyclooxygenase-2 (COX-2) inhibitors in the treatment of benign hypnic headache.

Lithium carbonate is used in the same manner as in the treatment of cluster headache and has its basis in use in its proven efficacy in the treatment of other diseases thought to have a chronobiological basis, such as cluster headache and bipolar disorders. However, the therapeutic window of lithium carbonate is small, and this drug should be used with caution.

A starting dose of 300 mg at bedtime may be increased after 48 hours to 300 mg twice per day. If no side effects are noted after 48 hours, the dose may be increased again to 300 mg three times per day.

Anecdotal reports exist that gabapentin and pregabalin also may be useful in decreasing the frequency and intensity of attacks of hypnic headache. Unlike with cluster headache, oxygen inhalation has been ineffective in aborting attacks of hypnic headache once the patient has been awakened by the pain.

Complications

Failure to diagnose hypnic headache correctly may put the patient at risk if an intracranial pathological condition or demyelinating disease, which may rarely mimic the clinical presentation of hypnic headache, is overlooked.

MRI and MRA are indicated in all patients thought to have hypnic headache. Failure to diagnose glaucoma, which also may cause intermittent ocular pain, may result in permanent loss of sight.

Clinical Pearls

Any patient presenting with nocturnal headaches should be taken very seriously.

Although statistically most of these headaches ultimately are proved to be of benign cause, a few patients have potentially life-threatening disease.

The diagnosis of hypnic headache is made by obtaining a thorough, targeted headache history and performing a careful physical examination.

The clinician must separate patients with hypnic headache from patients with headaches caused by an intracranial pathological condition such as tumors or systemic disease such as nocturnal arterial hypertension.

Patients with hypnic headache should have a normal neurological examination. If the neurological examination is abnormal, the diagnosis of benign hypnic headache should be discarded and a careful search for the cause of the patient’s neurological findings should be undertaken.

Sources

• Schwedt TJ: Thunderclap headaches: a focus on etiology and diagnostic evaluation. Headache 53(3):563-569, 2013. 
• Robbins MS, Evans RW: Primary and secondary stabbing headache. Headache 55:565-570, 2015. 
• Liang JF, Wang SJ: Hypnic headache: a review of clinical features, therapeutic options and outcomes. Cephalalgia 34:795-805, 2014.