Cluster headache

Cluster headache
Classification and external resources
Trigeminal nerve
ICD-10	G44.0
ICD-9	339.00,339.01,339.02,
DiseasesDB	2850
MedlinePlus	000786
eMedicine	EMERG/229 NEURO/67
MeSH	D003027

Cluster headache (CH) is a neurological disorder characterized by recurrent, severe headaches on one side of the head, typically around the eye.^[1] There are often accompanying autonomic symptoms during the headache such as eye watering, nasal congestion and swelling of and around the eye, all confined to the side of the head with the pain.^[1]

Cluster headache belongs to a group of primary headache disorders, classified as trigeminal autonomic cephalalgias or (TACs). The condition is named for the demonstrated grouping of headache attacks occurring together (cluster).^[1] Individuals typically experience repeated attacks of excruciatingly severe unilateral headache pain.^[2] CH attacks often occur periodically; spontaneous remissions may interrupt active periods of pain, though about 10–15% of chronic CH never remit.^[2] The cause has not been identified.

While there is no cure, cluster headaches can sometimes be prevented and acute attacks treated. The recommended treatment for acute attacks is oxygen in combination with a fast acting triptan.^[3] Primary recommended prevention is verapamil. Steroids may be used to prevent a recurrence until verapamil takes effect. The condition affects approximately 0.2% of the general population,^[4] and men are more commonly affected than women, by a ratio of about 2.5:1 to 3.5:1.^[1]

Signs and symptoms

Cluster headaches are recurring bouts of excruciating unilateral headache attacks^[5] of extreme intensity.^[6] The duration of a typical CH attack ranges from about 15 to 180 minutes.^[3] Most untreated attacks (about 75%) last less than 60 minutes.^[7]

The onset of an attack is rapid and most often without preliminary signs that are characteristic in migraine. Preliminary sensations of pain in the general area of attack, referred to as "shadows", may signal an imminent CH, or these symptoms may linger after an attack has passed, or even between attacks.^[8] Though a CH is strictly unilateral, there are some documented cases of "side-shift" between cluster periods, extremely rare, simultaneously (within the same cluster period) bilateral headache.^[9]

Pain

The pain occurs on one side only (unilateral), around the eye (orbital), particularly above the eye (supraorbital), in the temple (temporal), in any combination. The pain of CH is remarkably greater than in other headache conditions, including severe migraine. The term "headache" does not adequately convey the severity of the condition; the disease may be the most painful condition known to medical science.^[10] The pain is described as stabbing, burning or squeezing and may be located near or behind the eye and at the back of the head or neck.^[11]

Other symptoms

The typical symptoms of cluster headache are grouping (cluster) of recurring headache attacks of severe or very severe unilateral orbital, supraorbital and/or temporal pain. If left untreated, attack frequency will range from one attack every two days to eight attacks a day.^[2][3] The headache attack is accompanied by at least one of the following autonomic symptoms: drooping eyelid, pupil constriction, redness of the conjunctiva, tearing, runny nose, and, less commonly, facial blushing, swelling, or sweating, commonly but not always appearing on the same side of the head as the pain.^[2]

Restlessness (for example, pacing or rocking back and forth), photosensitivity, aversion to light (photophobia) or sensitivity to noise (phonophobia) may occur during a CH. Nausea is a rare symptom, although it has been reported.^[5] The neck may feel stiff or tender in the aftermath of a headache, with jaw or tooth pain sometimes present.^{[medical citation needed]} Secondary effects may include inability to organize thoughts and plans, physical exhaustion, confusion, agitation, aggressiveness, depression and anxiety.^[12]

People with CH may dread facing another headache and may adjust their physical or social activities seek assistance to accomplish seemingly normal tasks. They may hesitate to make plans because of the regularity, or conversely, the unpredictability of the pain schedule. These factors can lead to generalized anxiety disorders, panic disorder,^[13] serious depressive disorders,^[14] social withdrawal and isolation.^[15]

Recurrence

Cluster headaches are occasionally referred to as "alarm clock headaches" because of the regularity of their timing and they may awaken individuals from sleep. Both individual attacks and the cluster grouping can have a metronomic regularity; attacks striking at a precise time of day each morning or night is typical. The grouping of headache clusters can occur more often around solstices, or spring and autumn equinoxes, sometimes showing circannual periodicity. This has prompted researchers to speculate involvement, or dysfunction of the brain's hypothalamus, which controls the body's "biological clock" and circadian rhythm.^[16][17] Conversely, attack frequency may be highly unpredictable, showing no periodicity at all.

In episodic cluster headaches, attacks occur once or more daily, often at the same time each day, for a period of several weeks, followed by a headache-free period lasting weeks, months, or years. Approximately 10–15% of cluster headaches chronic, with multiple headaches occurring every day for years, sometimes without any remission.^{[medical citation needed]}

In accordance with the International Headache Society (IHS) diagnostic criteria, cluster headaches occurring in two or more cluster periods, lasting from 7 to 365 days with a pain-free remission of one month or longer between the clusters may be classified as episodic. If attacks occur for more than a year without pain-free remission of at least one month, the condition is classified chronic.^[2] Chronic CH occurs continuously without any remission periods between cycles; there may be high and low variation in cycles, meaning the frequency and severity of attacks may change without predictability, for a period of time. The amount of change during these cycles varies between individuals and does not demonstrate complete remission of the episodic form. The condition may change unpredictably, from chronic to episodic and from episodic to chronic.^[18] Remission periods lasting for decades have been known to occur.^{[medical citation needed]}

Causes

Positron emission tomography (PET) shows brain areas being activated during pain
Voxel-based morphometry (VBM) shows brain area structural differences

The cause of cluster headache is unknown.^[19]

Genetics

Cluster headache may, but rarely, run in some families in an autosomal dominant inheritance pattern.^[19] People with a first degree relative with the condition are about 14-48 times more likely to develop it themselves,^[1] and between 1.9 and 20% of persons with CH have a positive family history.^[19] This suggests that genetic factors are important, but the type and number of genes involved is unclear.^[19]

Smoking

About 65% of persons with CH are, or have been, tobacco smokers.^[1] Stopping smoking does not lead to improvement of the condition and CH also occurs in those who have never smoked (e.g. children);^[1] it is thought unlikely that smoking is a cause.^[1] People with CH may be predisposed to certain traits, including smoking or other lifestyle habits.^[20]

Hypothalamus

One theory is that the cause is dysfunction of the hypothalamus, which may explain why cluster headaches frequently strike around the same time each day, and during a particular season.^{[medical citation needed]} One of the functions of the hypothalamus is regulation of the biological clock. Metabolic abnormalities have also been reported.^{[medical citation needed]} The positron emission tomography (PET) scans indicate the brain areas which are activated during pain of attack only, compared to pain free periods. These pictures show brain areas which are active during pain in yellow/orange color (called "pain matrix"). The area in the center (in all three views) is specifically activated during CH only. The bottom row voxel-based morphometry (VBM) shows structural brain differences between individuals with and without CH; only a portion of the hypothalamus is different.^[21]

Pathophysiology

Cluster headache has been historically classified as vascular headaches; for decades, it has been proposed that intense pain was caused by dilation of blood vessels which was thought to create pressure on the trigeminal nerve. While this theory was thought to be the immediate cause of the pain, the etiology (underlying cause or causes) is not fully understood and CH pathogenesis is the subject of ongoing debate.^[22] Investigations into the vascular theory of headache disorders are helping to identify the role of other possible causative mechanisms in CH.^[23]

Diagnosis

Cluster headaches are often misdiagnosed, mismanaged, or undiagnosed for many years; they may be confused with migraine, "cluster-like" headache (or mimics), CH subtypes, other TACs, or other types of primary or secondary headache syndrome.^[24] Cluster-like head pain may be diagnosed as secondary headache rather than cluster headache.^[2]

A detailed oral history aids correct differential diagnosis, as there are no confirmatory tests for CH. A headache diary can be useful in tracking when and where pain occurs, how severe it is, and how long the pain lasts. A record of coping strategies used may help distinguish between headache type; data on frequency, severity and duration of headache attacks is a necessary tool for initial and correct differential diagnosis in headache conditions.^[25]

Correct diagnosis of CH is a challenge for practitioners, and is especially problematic in hospital emergency departments, where staff are not trained in the diagnosis of rare or complex chronic disease.^[26] Although experienced ER staff are sometimes trained to detect headache types,^[27] CH attacks themselves are not life-threatening.^[28]

Individuals with CH typically experience a lengthy delay before correct diagnosis.^[24][29] People are often misdiagnosed due to reported neck, tooth, jaw, and sinus symptoms and may unnecessarily endure many years of referral to ear, nose and throat (ENT) specialists for investigation of sinuses; dentists for tooth assessment; chiropractors and manipulative therapists for treatment; or psychiatrists, psychologists and other medical disciplines before their headaches are correctly diagnosed.^[30] Often there is a delay of several years before the correct diagnosis is reached.^[31] Medical students receive little training in differential diagnoses and management of headaches.^[32]

Differential

Cluster headache may be misdiagnosed as migraine or sinusitis.^[31] Other types of headache are sometimes mistaken for, or may mimic closely, CH. Incorrect terms like "cluster migraine" confuse headache types for both practitioner and patient, confound differential diagnosis and are often the cause of unnecessary diagnostic delay,^[33] ultimately delaying appropriate specialist treatment.

Headaches that may be confused with CH include:

• Chronic paroxysmal hemicrania (CPH) is a unilateral headache condition, without the male predominance usually seen in CH. Paroxysmal hemicrania may also be episodic. CPH typically responds "absolutely" to treatment with the anti-inflammatory drug indomethacin^[2] where in most cases CH typically shows no positive indomethacin response, making "Indomethacin response" an important diagnostic tool for specialist practitioners seeking correct differential diagnosis between the conditions.^{[medical citation needed]}
• Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a headache syndrome belonging to the group of TACs.^[2][34]
• Trigeminal neuralgia is a unilateral headache syndrome,^[30] or "cluster-like" headache.^[35]

Prevention

Preventive treatments are used to reduce or elimination cluster headache attacks; they are generally used in combination with abortive and transitional techniques.^[5]

Verapamil

The recommended first-line preventative therapy is verapamil, a calcium channel blocker.^[3][36] Verapamil was previously underused in people with cluster headache.^[5]

Steroids

There is little evidence to support a long-term benefit from steroids,^[3] but they may be used until other medications take effect as they appear to be effective at three days.^[3] They are generally discontinued after 8–10 days of treatment.^[5]

Surgery

Nerve simulators may be an option in the small number of people who do not improve with medications.^[37][38] Two procedures, deep brain stimulation or occipital nerve stimulation, may be useful;^[3] early experience shows a benefits in about 60% of cases.^[39] It typically takes weeks or months for this benefit to appear.^[38] A non-invasive method using transcutaneous electrical nerve stimulation (TENS) is being studied.^[38]

A number of surgical procedures, such as a rhizotomy or microvascular decompression, may also be considered,^[38] but evidence to support them is limited and there are cases of people ending up worse off.^[38]

Other

Lithium, methysergide, and topiramate are recommended alternative treatments,^[36][40] although there is little evidence supporting the use of topiramate or methysergide.^[3][41] This is also true for melatonin and ergotamine.^[3] Valproate, sumatriptan and oxygen are not recommended as preventative measures.^[3] Botox injection have shown mixed success.^[42]

Management

Treatment for cluster headache is divided into three primary categories: abortive, transitional, and preventative.^[43] There are two primary treatments for acute CH: oxygen and triptans,^[3] but they are underused due to misdiagnosis of the syndrome.^[5] During bouts of headaches, triggers such as alcohol, nitroglycerine and naps during the day should be avoided.^[7]

Oxygen

Oxygen therapy may help people with CH, but it does not help prevent future episodes.^[3] Typically it is given via a non-rebreather mask at 12-15 liters per minute for 15–20 minutes.^[3] Around 70% improve within 15 minutes.^[7] It is unclear if hyperbaric oxygen therapy is better than high flow oxygen.^[4]

Triptans

The other primarily recommended treatment of acute attacks is subcutaneous or intranasal sumatriptan.^[36] Sumatriptan and zolmitriptan have both been shown to improve symptoms during an attack with sumatriptan being superior.^[44] Because of the vasoconstrictive action of triptans, they are contraindicated in people with ischemic heart disease.^[3]

Opioids

The use of opioid medication in management of CH is not recommended;^[45] they may make headache syndromes worse^[46][47] and their long-term use is associated with dependency, addiction and withdrawal syndromes.^[48] Prescription of opioid medication may additionally lead to a delay in diagnosis, undertreatment, and mismanagement.^[45]

Other

The vasoconstricting ergot compounds may be useful,^[7] but have not been well studied in acute attacks.^[44]

Epidemiology

Cluster headache effects about 0.2% of the general population,^[4] or 56 to 326 people per 100,000.^[49] Males are effected more commonly than females, in a ratio of about 2.5:1 to 3.5:1.^[1] The condition usually starts between the ages of 20 and 50 years, although it can occur at any age.^[1]

History

The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926, who named the disease migrainous neuralgia.^[50][51][52] Descriptions of CH date to 1745 and probably earlier.^[53]

The condition was originally named Horton's cephalalgia after B.T. Horton, a US neurologist who postulated the first theory as to their pathogenesis. His original paper describes the severity of the headaches as being able to take normal men and force them to attempt or complete suicide; his 1939 paper said:

"Our patients were disabled by the disorder and suffered from bouts of pain from two to twenty times a week. They had found no relief from the usual methods of treatment. Their pain was so severe that several of them had to be constantly watched for fear of suicide. Most of them were willing to submit to any operation which might bring relief."^[54]

CH has alternately been called erythroprosopalgia of Bing, ciliary neuralgia, erythromelalgia of the head, Horton's headache, histaminic cephalalgia, petrosal neuralgia, sphenopalatine neuralgia, vidian neuralgia, Sluder's neuralgia, and hemicrania angioparalyticia.^[55]

Society and culture

Robert Shapiro, a professor of neurology, says that while cluster headaches are about as common as multiple sclerosis with a similar disability level, as of 2013, the US National Institutes of Health had spent $1.872 billion on research into multiple sclerosis in one decade, but less than $2 million on CH research in 25 years.^[56]

Research directions

Some controversial case reports suggest that ingesting LSD, psilocybin or cannabis can reduce pain and interrupt cluster headache cycles.^[57][58] A 2006 interview/survey of 53 individuals with CH said that psilocybin extended remission periods in 10% cases.^[58] The survey was not a blinded or controlled study, and was "limited by recall and selection bias", .^[57]

References

v t e Pathology of the nervous system, primarily CNS (G04–G47, 323–349) Inflammation Brain Encephalitis Viral encephalitis Herpesviral encephalitis Limbic encephalitis Encephalitis lethargica Cavernous sinus thrombosis Brain abscess Amoebic Spinal cord Myelitis: Poliomyelitis Demyelinating disease Transverse myelitis Tropical spastic paraparesis Epidural abscess Both/either Encephalomyelitis Acute disseminated Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders Basal ganglia disease Parkinsonism PD Postencephalitic NMS PKAN Tauopathy PSP Striatonigral degeneration Hemiballismus HD OA Dyskinesia Dystonia Status dystonicus Spasmodic torticollis Meige's Blepharospasm Athetosis Chorea Choreoathetosis Myoclonus Myoclonic epilepsy Akathisia Tremor Essential tremor Intention tremor Restless legs Stiff person Dementia Tauopathy Alzheimer's Early-onset Primary progressive aphasia Frontotemporal dementia/Frontotemporal lobar degeneration Pick's Dementia with Lewy bodies Posterior cortical atrophy Vascular dementia Mitochondrial disease Leigh's disease Demyelinating autoimmune Multiple sclerosis Neuromyelitis optica Schilder's disease hereditary Adrenoleukodystrophy Alexander Canavan Krabbe ML PMD VWM MFC CAMFAK syndrome Central pontine myelinolysis Marchiafava-Bignami disease Alpers' disease Episodic/ paroxysmal Seizure/epilepsy Focal Generalised Status epilepticus Myoclonic epilepsy Headache Migraine Familial hemiplegic Cluster Tension Cerebrovascular TIA Amaurosis fugax Transient global amnesia Acute aphasia Stroke MCA ACA PCA Foville's Millard-Gubler Lateral medullary Weber's Lacunar stroke Sleep disorders Insomnia Hypersomnia Sleep apnea Obstructive Ondine's curse Narcolepsy Cataplexy Kleine-Levin Circadian rhythm sleep disorder Advanced sleep phase disorder Delayed sleep phase disorder Non-24-hour sleep–wake disorder Jet lag CSF Intracranial hypertension Hydrocephalus/NPH Choroid plexus papilloma Idiopathic intracranial hypertension Cerebral edema Intracranial hypotension Other Brain herniation Reye's Hepatic encephalopathy Toxic encephalopathy Hashimoto's encephalopathy Spinal cord/ myelopathy Syringomyelia Syringobulbia Morvan's syndrome Vascular myelopathy Foix-Alajouanine syndrome Spinal cord compression Both/either Degenerative SA Friedreich's ataxia Ataxia telangiectasia MND UMN only: Primary lateral sclerosis Pseudobulbar palsy Hereditary spastic paraplegia LMN only: Distal hereditary motor neuropathies Spinal muscular atrophies SMA SMAX1 SMAX2 DSMA1 Congenital DSMA SMA-PCH SMA-LED SMA-PME Progressive muscular atrophy Progressive bulbar palsy Fazio–Londe Infantile progressive bulbar palsy both: Amyotrophic lateral sclerosis M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D)

v t e CNS disease: Headache (G43–G44, 339, 346) Primary ICHD 1 Migraine Familial hemiplegic Retinal migraine ICHD 2 Tension ICHD 3 Cluster Chronic paroxysmal hemicrania SUNCT ICHD 4 Hemicrania continua Thunderclap headache Coital cephalalgia New daily persistent headache Hypnic headache Secondary ICHD 5 Migralepsy ICHD 7 Ictal headache Post-dural-puncture headache ICHD 8 Hangover Medication overuse headache ICHD 13 Trigeminal neuralgia Occipital neuralgia External compression headache Cold-stimulus headache Optic neuritis Postherpetic neuralgia Tolosa-Hunt syndrome Other Vascular M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D)