Cluster Headache: a Review MARILYN J
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• Cluster headache: A review MARILYN J. CONNORS, DO ID Cluster headache is a debilitat consists of episodes of excruciating facial pain that ing neuronal headache with secondary vas is generally unilateraP and often accompanied by cular changes and is often accompanied by ipsilateral parasympathetic phenomena including other characteristic signs and symptoms, such nasal congestion, rhinorrhea, conjunctival injec as unilateral rhinorrhea, lacrimation, and con tion, and lacrimation. Patients may also experi junctival injection. It primarily affects men, ence complete or partial Horner's syndrome (that and in many cases, patients have distinguishing is, unilateral miosis with normal direct light response facial, body, and psychologic features. Sever and mild ipsilateral ptosis, facial flushing, and al factors may precipitate cluster headaches, hyperhidrosis).4-6 These autonomic disturbances including histamine, nitroglycerin, alcohol, sometimes precede or occur early in the headache, transition from rapid eye movement (REM) adding credence to the theory that this constella to non-REM sleep, circadian periodicity, envi tion of symptoms is an integral part of an attack and ronmental alterations, and change in the level not a secondary consequence. Some investigators of physical, emotional, or mental activity. The consider cluster headache to exemplify a tempo pathophysiologic features have not been com rary and local imbalance between sympathetic and pletely elucidated, but the realms of neuro parasympathetic systems via the central nervous biology, intracranial hemodynamics, endocrinol system (CNS).! ogy, and immunology are included. Therapy The nomenclature of this form of headache in is prophylactic or abortive (or both). Treat the literature is extensive and descriptive, includ ment, possibly with combination regimens, ing such terminology as histamine cephalgia, ery should be tailored to the needs of the indi thromelalgia of the head, red migraine, atypical vidual patient. facial neuralgia, ipsilateral redness of the face, (Key words: Neuronal headache, vascular sphenopalatine neuralgia, greater superficial pet headache, parasympathetic, circadian peri rosal neuralgia, and Horton's headache.3,7-9 odicity, hemodynamics, immunology, pro phylactic therapy, abortive therapy, chronic Clinical features cluster headache, episodic cluster headache, Cluster headaches occur predominantly in white histamine, nitroglycerin, alcohol, REM sleep, men, with a male-to-female ratio of 5:1.3-5 The aver non-REM sleep, substance P, serotonin, central age age at onset is in the late 20s to 40s, but clus opiates) ter headache may afflict anyone.3,lO The incidence of cluster headache is 0.40% in males and 0.08% in Thus did I become acquainted early on with the three females.3,5 Individuals who suffer from cluster Ps of cluster headache, the pain, the pattern and the headaches are often described as ''leonine'' in appear parasympathetic phenomena that distinguish this most ance, with a particularly masculine body habitus distressing of headaches to which, now, we may be adding including tall stature, thick skin folds, coarse facial substance P .1 skin with telangiectasias, broad chin, and well Cluster headache was first documented in med chiseled lower lip.l,3,8,lO Cluster headache patients icalliterature at the turn of the 20th century.!,2 It very often have hazel eyes and smoke and drink is primarily a neuronal headache with secondary alcohol more than the average person.3,5 vascular changes and therefore involves alterations A great deal of controversy exists regarding in the caliber of cerebral blood vessels (that is, the psychologic profile of these individuals. Inves vasoconstriction/vasodilation). Cluster headache tigators have noted that these patients are ambi tious, perfectionist, hypochondriacal, and depen dent personalities who may display unhealthy Correspondence to Marilyn J . Connors, DO, Department of Family Practice, Scripps Clinic Medical Group, Inc, 3835 Avo strategies for coping with anger.!,4,5,7,8,1l-16 To date, cado Blvd, La Mesa, CA 91941. no conclusive evidence exists to support an inher- Review article • Connors JAOA · Vol 95 • No 9 · September 1995 • 533 ent psychopathologic matrix in cluster headache 3 Table patients. A family history is rarely present. ,5 Factors Precipitating Cluster Headaches Cluster headaches occur in groups, or clusters, of attacks, with headache-free periods of remis sion. They can be episodic (remissions of 1 year or o Subcutaneous injection more), or chronic (no sustained remissions).2,9,17 of histamine Chronic cluster headaches occur at least twice a o Subcutaneous injection of nitroglycerin week for 2 years or more without remission. Between o Alcohol consumption 80% and 97% of sufferers have episodic cluster o Transition from REM to non-REM sleep headaches, and the remaining 3% to 20% have o Environmental changes chronic headaches.2,10 Chronic cluster headaches o Circadian rhythm are further differentiated into two subgroups (pri o Decrease in level of activity mary, chronic pattern de novo; and secondary, evo lution of episodic cluster pattern to a chronic pat tern).8 Cluster periods usually range from 6 to 12 ation. This theory encompasses the concept that a weeks.5,18 switch from the parasympathetic cholinergic sys The pain is typically of sudden onset and is tem (that is, the predominant neurotransmitters described as a burning, stabbing, or boring sensa of REM sleep) to a primarily sympathetic, aminer tion in the eye, temple, forehead, jaw, or teeth, gic, especially serotoninergic system (that is, the with occasional radiation to the ear or neck.4,l9 The mediators of non-REM sleep) provokes cluster duration of a cluster headache is usually 30 min headache. Many cluster headache patients are awak utes to 2 hourS.1-3 Attacks often occur in the evening ened from a sound sleep and recall a vivid dream. or within 2 hours of the patient's falling asleep, During REM sleep, many physiologic changes occur and the pain awakens the patient.1,19 Patients may affecting heart rate, lacrimation, body temperature, have 1 to 15 attacks per day.2,3 Cluster headache gastric acid secretion, miosis, sweating, dreaming, patients are rarely quiescent, but are more often pac and vasodilation, which exemplifies a heightened ing, rocking, or moving about, and they even may parasympathetic state.l This theory may parallel display bizarre behaviors (for example, violence, the increased incidence of cluster headache when suf fugues, transvestism, trancelike states, and even con ferers change from a state of activity to inactivity templation of suicide). 1,4 (for example, difference between work and home or work and vacation) and is related to a decrease Precipitating factors in overall vasomotor tone. Factors that have been reported to precipitate clus Sudden changes in environment (changes in ter headaches (Table ) include subcutaneous injec temperature, time zone, barometric pressure, tion of histamine and nitroglycerin,2,3,5,10 the use etcetera) are associated with an increased inci of alcohol during a cluster period,1,5 the transition dence of cluster headache. 1 Seasonal variations from rapid eye movement (REM) to non-REM sleep, also appear to affect cluster cycles, and it is often environmental alterations, circadian periodicity, 1-3 reported that spring and fall are particularly and change in level of physical, emotional, or intel adverse.5,10 Circadian rhythm has been implicat lectual activity. 1 ed as a factor, in that many patients have anoth Horton2 demonstrated that subcutaneous injec er episode 12 or 24 hours after their last bout on suc tion of histamine reproduces the symptoms of clus cessive days.1-3 ter headache within 5 to 45 minutes, and this was once used as a diagnostic test.2,5 Nitroglycerin sub Differential diagnosis cutaneously injected also induces cluster headache Cluster headache can be differentiated from a vari in most patients. Alcohol consumption during a ety of entities on the basis of several unique char cluster cycle precipitates attacks. 1,3,5 All three sub acteristics, including male preponderance, absence stances are cerebral vasodilators and may trigger of aura or prodrome, brevity of attacks, pattern of cluster headache by operating on a preexisting occurrence, and behavior of patient during an attack. decrease in vasomotor tone, causing excessive vasodi The differential diagnosis includes migraine lation. It has been proposed that these substances headache, chronic paroxysmal hemicrania, trigem cause a reflex vasoconstriction that mediates changes inal neuralgia, temporal arteritis, Raeder's para in blood flow, consequently causing pain.1,5 Sub trigeminal syndrome, pheochromocytoma associated stance P has been implicated in this potential path with headache, and acute scenarios such as acute way. 1,3,20,21 sinusitis and acute pathologic headache. Several investigators1,5,22 have proposed that cluster headache is related to a transition from a state Pathophysiologic features of relative arousal or activity to a state of relax- There exists a multitude of hypotheses regarding 534· JAOA · Vol 95 • No 9 · September 1995 Review article • Connors the pathophysiologic process of cluster headaches. met-enkephalin levels in patients with cluster Theories encompass the realms of neurobiology (for headache and normal or even slightly elevated l3-endor example, central opiate activity, substance P, his phin levels.24,25 Because