Cluster headache

Cluster headaches are recurring bouts of severe unilateral headache attacks. The duration of a typical cluster headache ranges from about 15 to 180 minutes. However, women may have longer and more severe cluster headaches. The onset of an attack is rapid and typically without an aura. Preliminary sensations of pain in the general area of attack, referred to as "shadows", may signal an imminent cluster headache, or these symptoms may linger after an attack has passed, or between attacks. Though cluster headaches are strictly unilateral, there are some documented cases of "side-shift" between cluster periods, or, rarely, simultaneous (within the same cluster period) bilateral cluster headaches. Pain The pain occurs only on one side of the head, around the eye, particularly behind or above the eye, in the temple. The pain is typically greater than in other headache conditions, including migraines, and is usually described as burning, stabbing, drilling or squeezing. While suicide is rare, those with cluster headaches may experience suicidal thoughts (giving the alternative name "suicide headache" or "suicidal headache"). Dr. Peter Goadsby, Professor of Clinical Neurology at University College London, and Chair and Patron of OUCH(UK), a leading researcher on the condition has commented: Other symptoms The typical symptoms of cluster headache include grouped occurrence and recurrence (cluster) of headache attack, severe unilateral orbital, supraorbital and/or temporal pain. If left untreated, attack frequency may range from one attack every two days to eight attacks per day. social withdrawal and isolation. Cluster headaches have been recently associated with obstructive sleep apnea comorbidity. Recurrence Cluster headaches may occasionally be referred to as "alarm clock headache" because of the regularity of their recurrence. Cluster headaches often awaken individuals from sleep. Both individual attacks and the cluster grouping can have a metronomic regularity; attacks typically strike at a precise time of day each morning or night. The recurrence of headache cluster grouping may occur more often around solstices, or seasonal changes, sometimes showing circannual periodicity. Conversely, attack frequency may be highly unpredictable, showing no periodicity at all. These observations have prompted researchers to speculate an involvement or dysfunction of the hypothalamus. The hypothalamus controls the body's "biological clock" and circadian rhythm. In episodic cluster headache, 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 are chronic, with multiple headaches occurring every day for years, sometimes without any remission. 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 headache attacks may be classified as episodic. If headache attacks occur for more than a year without pain-free remission of at least three months, the condition is classified as chronic. Chronic cluster headaches both occur and recur without any remission periods between cycles; there may be variation in cycles, meaning the frequency and severity of attacks may change without predictability for a period of time. The frequency, severity, and duration of headache attacks experienced by people 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. ==Causes==

The specific causes and pathogenesis of cluster headaches are not fully understood. Some experts consider the posterior hypothalamus to be important in the pathogenesis of cluster headaches. This is supported by a relatively high success ratio of deep-brain stimulation therapy on the posterior hypothalamic grey matter. Genetics Cluster headache may run in some families in an autosomal dominant inheritance pattern. People with a first degree relative with the condition are about 14–48 times more likely to develop it themselves, Several studies have found a higher number of relatives affected among females. Hypothalamus A review suggests that the suprachiasmatic nucleus of the hypothalamus, which is the major biological clock in the human body, may be involved in cluster headaches, because cluster headaches occur with diurnal and seasonal rhythmicity. Positron emission tomography (PET) scans indicate the brain areas which are activated during attack only, compared to pain free periods. These pictures show brain areas that are active during pain in yellow/orange color (called "pain matrix"). The area in the center (in all three views) is activated only during cluster headaches. The bottom row voxel-based morphometry shows structural brain differences between individuals with and without CH; only a portion of the hypothalamus is different. ==Diagnosis==

Cluster-like head pain may be diagnosed as secondary headache rather than cluster headache. Correct diagnosis presents a challenge as the first cluster headache attack may present where staff are not trained in the diagnosis of rare or complex chronic disease. While cluster headache attacks themselves are not directly life-threatening, suicide ideation has been observed. Individuals with cluster headaches typically experience diagnostic delay before correct diagnosis. 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. Under-recognition of cluster headaches by health care professionals is reflected in consistent findings in Europe and the United States that the average time to diagnosis is around seven years. Other types of headache are sometimes mistaken for, or may mimic closely, cluster headaches. Incorrect terms like "cluster migraine" confuse headache types, confound differential diagnosis and are often the cause of unnecessary diagnostic delay, ultimately delaying appropriate specialist treatment. Other types of headaches that may be confused with cluster headache include: • Chronic paroxysmal hemicrania is a unilateral headache condition, without the male predominance usually seen in cluster headaches. Paroxysmal hemicrania may also be episodic but the episodes of pain seen in chronic paroxysmal hemicrania are usually shorter than those seen with cluster headaches. Chronic paroxysmal hemicrania typically responds "absolutely" to treatment with the anti-inflammatory drug indomethacin • Hemicrania continua • Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a headache syndrome belonging to the group of TACs. • Trigeminal neuralgia is a unilateral headache syndrome, ==Prevention==

Management for cluster headache is divided into three primary categories: abortive, transitional, and preventive. Preventive treatments are used to reduce or eliminate cluster headache attacks; they are generally used in combination with abortive and transitional techniques. Verapamil was previously underused in people with cluster headache. Preventive therapy with verapamil is believed to work because it has an effect on the circadian rhythm and on CGRPs as CGRP-release is controlled by voltage-gated calcium channels. Surgery Nerve stimulators may be an option in the small number of people who do not improve with medications. Two procedures, deep brain stimulation or occipital nerve stimulation, may be useful; It typically takes weeks or months for this benefit to appear. although there is little evidence supporting the use of topiramate or methysergide. This is also true for tianeptine, melatonin, and ergotamine. Evidence for baclofen, botulinum toxin, and capsaicin is unclear. ==Management==

There are two primary treatments for acute CH: oxygen and triptans, Hyperbaric oxygen at pressures of ~2 times greater than atmospheric pressure may relieve cluster headaches. Sumatriptan and zolmitriptan have both been shown to improve symptoms during an attack with sumatriptan being superior. Because of the vasoconstrictive side-effect of triptans, they may be contraindicated in people with ischemic heart disease. Long-term opioid use is associated with well known dependency, addiction, and withdrawal syndromes. Prescription of opioid medication may additionally lead to further delay in differential diagnosis, undertreatment, and mismanagement. Other Intranasal lidocaine (sprayed in the ipsilateral nostril) may be an effective treatment with patient resistant to more conventional treatment. Sub-occipital steroid injections have shown benefit and are recommended for use as a transitional therapy to provide temporary headache relief as more long term prophylactic therapies are instituted. A 2024 research found that exercise could relieve CH pain for significant percentage of people. ==Epidemiology==

Cluster headache affects about 0.1% of the general population at some point in their life. ==History==

The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926, who named the disease migrainous neuralgia. Descriptions of cluster headache date to 1745 and probably earlier. The condition was originally named Horton's cephalalgia after Bayard Taylor 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 die by suicide; his 1939 paper said: 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, Sluder's syndrome, and hemicrania angioparalyticia. == 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 cluster headache research in 25 years. == Research directions ==

Some case reports suggest that ingesting lysergamides such as LSD, tryptamines such as psilocybin (as found in hallucinogenic mushrooms), or DMT can abort attacks and interrupt cluster headache cycles. The hallucinogen DMT has a chemical structure that is similar to the triptan sumatriptan, indicating a possible shared mechanism in preventing or stopping migraine and TACs. In Canada, a first cluster headache patient was granted approval to receive treatment with psilocybin under the country's Special Access Program. Fremanezumab, a humanized monoclonal antibody directed against calcitonin gene-related peptides alpha and beta, was in phase 3 clinical trials for cluster headaches, but the studies were stopped early due to a futility analysis demonstrating that a successful outcome was unlikely. ==References==