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Cluster headache
Classification and external resources

The Cluster Headache by JD Fletcher
ICD-10 G44.0
ICD-9 339.00,339.01,339.02,
DiseasesDB 2850
eMedicine EMERG/229 NEURO/67
MeSH D003027

Cluster headache, nicknamed "suicide headache", is a neurological disease that involves, as its most prominent feature, an immense degree of pain. "Cluster" refers to the tendency of these headaches to occur periodically, with active periods interrupted by spontaneous remissions. The cause of the disease is currently unknown. It affects approximately 0.1% of the population, and men are more commonly affected than women.

Contents

Signs and symptoms

Cluster headaches are excruciating unilateral headaches,[1] of extreme intensity.[2] The duration of the common attack ranges from as short as 15 minutes to three hours or more. The onset of an attack is rapid, and most often without the preliminary signs that are characteristic of a migraine. However, some sufferers report preliminary sensations of pain in the general area of attack, often referred to as "shadows", that may warn them an attack is imminent. Though the headaches are almost exclusively unilateral, there are some documented as cases of "side-shifting" between cluster periods, or, even rarer, simultaneously (within the same cluster period) bilateral headache.[3] Trigeminal neuralgia can also bring on headaches with similar qualities. However, with Trigeminal neuralgia the pain is mostly located around the "cheek" area and is described as being more lance-like in quality.

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Pain

The pain of cluster headaches is markedly greater than in other headache conditions, including severe migraines; experts have suggested that it may be the most painful condition known to medical science. Female patients have reported it as being more severe than childbirth.[4] Dr. Peter Goadsby, Professor of Clinical Neurology at University College London, a leading researcher on the condition has commented:

"Cluster headache is probably the worst pain that humans experience. I know that’s quite a strong remark to make, but if you ask a cluster headache patient if they’ve had a worse experience, they’ll universally say they haven't. Women with cluster headache will tell you that an attack is worse than giving birth. So you can imagine that these people give birth without anesthetic once or twice a day, for six, eight, or ten weeks at a time, and then have a break. It's just awful."[5]

The pain is lancinating or boring in quality, and is located behind the eye (periorbital) or in the temple, sometimes radiating to the neck or shoulder. Analogies frequently used to describe the pain are a red-hot poker inserted into the eye, or a spike penetrating from the top of the head, behind one eye, radiating down to the neck, or sometimes having a leg amputated without any anaesthetic. The condition was originally named Horton's Neuralgia after Dr. B.T Horton, 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 commit suicide. From Horton's 1939 paper on cluster headache:

"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."[6]

Indeed, cluster headaches are also known by the nickname "suicide headaches".[7]

Other symptoms

The cardinal symptoms of the cluster headache attack are the severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes, if untreated, and the attack frequency of one to 16 attacks in 48 hours. The headache is accompanied by at least one of the following autonomic symptoms: ptosis (drooping eyelid), miosis (pupil contraction) conjunctival injection (redness of the conjunctiva - the covering of the eyeball), lacrimation (tearing), rhinorrhea (runny nose), and, less commonly, facial blushing, swelling, or sweating, all appearing on the same side of the head as the pain.[8] The attack is also associated with restlessness, the sufferer often pacing the room or rocking back and forth. Less frequently, he or she will have an aversion to bright lights and loud noise during the attack. Nausea rarely accompanies a cluster headache, though it has been reported. The neck is often stiff or tender in the aftermath of a headache, with jaw or tooth pain sometimes present. Some sufferers report feeling as though their nose is stopped up and that they are unable to breathe out of one of their nostrils.

Cyclical recurrence and regular timing

Cluster headaches are occasionally referred to as "alarm clock headaches", because of its ability to wake a person from sleep, and because of the regularity of its timing in that both the individual attacks and the clusters themselves can have a metronomic regularity; attacks striking at a precise time of day each morning or night is typical, even precisely at the same time a week later. This has prompted researchers to speculate an involvement of the brain's "biological clock" or circadian rhythm.

Episodic or chronic

In episodic cluster headache, these attacks occur once or more daily, often at the same times each day, for a period of several weeks, followed by a headache-free period lasting weeks, months, or years. Approximately 10–15% of cluster headache sufferers are chronic; they can experience multiple headaches every day for years.

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 are considered episodic. If the attacks occur for more than a year without a pain-free remission of at least one month, the condition is considered chronic.[9] Chronic clusters run continuously without any "remission" periods between cycles. The condition may change from chronic to episodic and from episodic to chronic. Remission periods lasting for decades before the resumption of clusters have been known to occur.

Other types of headache

There are other types of headache that are sometimes mistaken for cluster headaches.

  • Some people with extreme headaches of this nature (especially if they are not unilateral) may actually have an ictal headache. Anti-convulsant medications can significantly improve this condition so sufferers should consult a physician about this possibility.[11]
  • It is also possible to have two or more different types of headaches, complicating diagnosis and treatment.

Pathophysiology

Gray's FIG. 778– Trigeminal nerve is shown in yellow.
Gray's FIG. 777– Detailed view of ophthalmic nerve, shown in yellow.

Cluster headaches have been classified as vascular headaches. The intense pain is caused by the dilation of blood vessels which creates pressure on the trigeminal nerve. While this process is the immediate cause of the pain, the etiology (underlying cause or causes) is not fully understood.


Recently, researchers have linked low testosterone as a possible cause of cluster headaches.[12][13]

Hypothalamus

Among the most widely accepted theories is that cluster headaches are due to an abnormality in the hypothalamus; Dr Goadsby, an Australian specialist in the disease has developed this theory. This can explain why cluster headaches frequently strike around the same time each day, and during a particular season, since one of the functions the hypothalamus performs is regulation of the biological clock. Metabolic abnormalities have also been reported in patients.

The hypothalamus is responsive to light—daylength and photoperiod; olfactory stimuli, including pheromones; steroids, including sex steroids and corticosteroids; neurally transmitted information arising in particular from the heart, the stomach, and the reproductive system; autonomic inputs; blood-borne stimuli, including leptin, ghrelin, angiotensin, insulin, pituitary hormones, cytokines, blood plasma concentrations of glucose and osmolarity, etc.; and stress. These particular sensitivities may underlay the causes, triggers, and methods of treatment of cluster headache.

Neuroimaging
PET1.jpg
PET2.jpg
PET3.jpg
Positron emission tomography (PET) shows brain areas being activated during pain
VBM1.jpg
VBM2.jpg
VBM3.jpg
Voxel-based morphometry (VBM) shows brain area structural differences

The above Positron emission tomography (PET) pictures indicate the brain areas which are activated during pain only, compared to the pain free periods. These pictures show brain areas which are always active during pain in yellow/orange colour (called "pain matrix"). The area in the centre (in all three views) is specifically activated during cluster headache only. The bottom row Voxel-based morphometry (VBM) pictures show structural brain differences between cluster headache patients and people without headaches; only a portion of the hypothalamus is different.[14][15]

Genetics

There is a genetic component to cluster headaches, although no single gene has been identified as the cause. First-degree relatives of sufferers are more likely to have the condition than the population at large.[16] However, genetics appears to play a much smaller role in cluster headache than in some other types of headaches.

Triggers

Nitroglycerin (glyceryl trinitrate) can sometimes induce cluster headaches in sufferers in a manner similar to spontaneous attacks. Ingestion of alcohol or chocolate is recognized as a common trigger of cluster headaches when a person is in cycle or susceptible. Exposure to hydrocarbons (petroleum solvents, perfume) is also recognized as a trigger for cluster headaches. Some patients have a decreased tolerance to heat, and becoming overheated may act as a trigger which may explain the occurrence after aerobic exercise. Napping causes a headache for some sufferers, while for others lack of sleep triggers them. The role of diet and specific foods in triggering cluster headaches is controversial and not well understood.

Smoking

Nicotine may trigger cluster headaches, and the affliction is often found in people with a heavy addiction to cigarette smoking.[17]

Diagnosis

Cluster headaches often go undiagnosed for many years, being confused with migraine or other causes of headache.[18]

Cluster headaches are benign, but because of the extreme and debilitating pain associated with them, and potential risk of suicide, a severe attack is nevertheless treated as a medical emergency. Because of the relative rareness of the condition and ambiguity of the symptoms, some sufferers may not receive treatment in the emergency room and people may even be mistaken as exhibiting drug-seeking behavior.

Management

Over-the-counter pain medications (such as aspirin, paracetamol, and ibuprofen) typically have no effect on the pain from a cluster headache. Unlike other headaches such as migraines and tension headaches, cluster headaches do not respond to biofeedback.[citation needed]

Medications to treat cluster headaches are classified as either abortives or prophylactics (preventatives). In addition, short-term transitional medications (such as steroids) may be used while prophylactic treatment is instituted and adjusted. With abortive treatments often only decreasing the duration of the headache and preventing it from reaching its peak rather than eliminating it entirely, preventive treatment is always indicated for cluster headaches, to be started at the first sign of a new cluster cycle.

Abortive treatment

During the onset of a cluster headache, some people respond to inhalation of 100% oxygen (12-15 litres per minute in a non-re-breathing mask).[19][20][21] When used at the onset this can abort the attack in as little as 1 minute or as long as 10 minutes. Once an attack is at its peak, oxygen therapy appears to have little effect so many people have an oxygen tank close. Alternative first-line treatment is subcutaneous administration of sumatriptan.[20] Hyperbaric oxygen therapy has been used successfully in treating cluster headaches though it was not shown to be more successful than surface oxygen.[22][23][24]

The injectable form of sumatriptan has been shown to abort a cluster headache within fifteen minutes in 96% of cases.[25]

Some non-narcotic treatments that have shown mixed levels of success are botox injections along the occipital nerve, as well as sarapin (pitcher plant extract) injections.[26][27]

Lidocaine and other topical anesthetics sprayed into the nasal cavity may relieve or stop the pain,[28] normally in a few minutes, but long term use is not suggested due to the side effects and possible damage to the nasal cavities.

Previously, vaso-constrictors such as ergot compounds were also used, and sufferers report a similar relief by taking strong cups of coffee immediately at the onset of an attack. Cafergot, a cheap off-the-shelf vaso-constrictor, has been shown to stop cluster headaches within 40 minutes of ingestion.

Other abortive remedies that work for some include ice, hot showers, cool or lukewarm water sprayed on the face around the sinus, temple, and ear areas, breathing cold air, application of White Flower analgesic balm beneath the nostrils, caffeine, and drinking large amounts of water in the early stages of an attack. Vigorous exercise has been shown in some cases to be very effective in relieving and aborting an acute attack by increasing the levels of oxygen within the body. This could also be due to an increase in adrenaline and changes in blood pressure. Some people report that sexual intercourse and specifically orgasm may terminate an attack possibly by acutely modulating hypothalamic function. Concentrating one's thoughts to a remote part of one's anatomy, such as the opposite little toe, reduced the length of attacks. Headaches are self-perpetuating by concentrating the mind on the symptoms.[29][30][31]

Prophylactic treatment

A wide variety of prophylactic medicines are in use, and patient response to these is highly variable. Current European guidelines suggest the use of the calcium channel blocker verapamil at a dose of at least 240 mg daily. Steroids, such as prednisolone, are also effective, with a high dose given for the first five days or longer before tapering down. Methysergide, lithium and the anticonvulsant topiramate are recommended as alternative treatments.[20]

Intravenous magnesium sulfate relieves cluster headaches in about 40% of patients with low serum ionized magnesium levels.[32] Melatonin has also been demonstrated to bring significant improvement in approximately half of episodic patients.[33] Kudzu root supplements have also been reported beneficial by some cluster headaches patients. [34]

Low-dose psychedelics

There is anecdotal evidence that serotonergic psychedelics such as psilocybin (mushrooms) and LSD and LSA (d-Lysergic acid amide, contained by Rivea corymbosa seeds) abort cluster periods and extend remission periods. The doses needed for the effect on cluster headaches are below those needed to produce psychedelic effects.[35][36][37] Melatonin, psilocybin, serotonin, and the triptan abortive drugs are closely-related tryptamines.

Dr. Andrew Sewell and Dr. John Halpern at McLean Hospital in Boston have investigated the ability of psilocybin ("magic mushrooms") and LSD to treat cluster headaches. These researchers examined medical records of 53 patients who had taken hallucinogenic mushrooms and reported in Neurology that the majority of them found partial or complete relief from cluster attacks.[38] A clinical study of these treatments under the auspices of Clusterbusters is being developed by Dr. Halpern and colleagues at Harvard Medical School, McLean Hospital. The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. [39][40]

2-Bromo-LSD (BOL), a non-hallucinogenic derivative of LSD, delivered promising results in a small clinical trial in four patients.[41]

Within the United States, the Controlled Substances Act (CSA) of 1970 makes it illegal to possess hallucinogens (including psilocybin and LSD), classifying them as Schedule I drugs with no legitimate medical use. Patients who use psilocybin to treat their symptoms face legal prosecution, although there are no known convictions.

Epidemiology

While migraines are diagnosed more often in women, cluster headaches are more prevalent in men. The male-to-female ratio in cluster headache ranges from 4:1 to 7:1. It primarily occurs between the ages of 20 to 50 years.[42] This gap between the sexes has narrowed over the past few decades, and it is not clear whether cluster headaches are becoming more frequent in women, or whether they are merely being better diagnosed. Limited epidemiological studies have suggested prevalence rates of between 56 and 326 people per 100,000.[43]

History

The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926. He named the disease Migrainous neuralgia.[44][45][46]

Cluster headaches have been called by several other names in the past including Erythroprosopalgia of Bing, Ciliary neuralgia, Erythromelagia of the head, Horton's headache (named after Bayard T. Horton, an American neurologist), Histaminic cephalalgia, Petrosal neuralgia, sphenopalatine neuralgia, Vidian neuralgia, Sluder's neuralgia, and Hemicrania angioparalyticia.[47] Sluder's neuralgia (syndrome) and cluster pain can often be temporarily stopped with nasal lidocaine drops.[48][49]

See also

References

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