CLUSTER AND RELATED HEADACHES

Lawrence C. Newman 1 2 MD
Peter Goadsby 3 MD
Richard B. Lipton 1 MD

1 Department of Neurology, Albert Einstein College of Medicine, Bronx (LCN, RBL)
2 Headache Institute, St. Luke's-Roosevelt Hospital Center, New York (LCN), New York
3 Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, United Kingdom (PG)

Address reprint requests to
Lawrence C. Newman, MD
The Headache Institute
St. Luke's-Roosevelt Hospital Center
1000 Tenth Avenue
New York, NY 10019

CLUSTER HEADACHE

Cluster headache is a well-described syndrome characterized by discrete bouts of excruciatingly severe unilateral headaches associated with ipsilateral cranial autonomic features. Although relatively uncommon, this disorder is important to physicians treating patients with headache because the sufferers tend to be desperate, often misdiagnosed, and often mismanaged.
Epidemiology

Cluster headache is a rare disorder affecting approximately 0.1% of the population.[18] [28] The disorder affects men more often than women with the sex ratio ranging from 3.5 to 6.7:1.[47] [52] The male-to-female ratio, based on the year of onset of the disorder, has decreased from 6.2:1 in the 1960s to 2.1:1 in the 1990s.[52] More recent evidence suggests that cluster, similar to migraine, may have a familial predisposition; Russell et al[87] reported a 14-fold risk of cluster headache among first-degree relatives with the disorder.

Clinical Features

The International Headache Society (IHS) divides cluster headache into two subtypes, episodic and chronic cluster.[40] The chronic form is sub classified further into primary and secondary variants; the distinction is based on the presence or absence of prior episodic cluster attacks.

Most patients suffer from episodic cluster headaches in which attacks recur for weeks to months at a time (the cluster period), then are separated by months or years of pain freedom (the remission period). The IHS mandates that episodic cluster consists of headache attacks that occur in periods lasting 1 week to 1 year and are separated by pain-free periods lasting 14 days or more. When remission periods last less than 14 days or when attacks recur without remission for more than 1 year, the designation chronic cluster is given. Approximately 10% of sufferers never experience remissions. The chronic subtype may evolve from an initially episodic course (secondary chronic cluster) or may begin de novo (primary chronic).

Cluster headache is so named because attacks occur in groups or clusters separated by periods of pain-free remissions. The mean age of onset is 28 to 30 years, although attacks may begin during childhood or in later life. During the cluster period, attacks may recur once per week, or eight attacks per day may occur.[40] [116] Most patients experience one to two attacks daily.[27] The individual attacks usually are brief, lasting 30 to 180 minutes each (mean, 45 minutes). Attacks tend to recur at the same time each day and are notable in that they often occur at night, awakening the patient from a sound sleep. A seasonal preponderance occurs, with cluster phase often occurring in the spring or autumn months.

Attacks of cluster are excruciatingly severe; unilateral (usually without side-shift); and of maximal intensity in, around, or behind the eye. The pain may radiate into the ipsilateral temple, neck, jaw, or upper teeth and frequently is misdiagnosed as sinus or dental disease. Rarely the pain may occur on the opposite side of the head in a subsequent cluster cycle; rarer still, in some patients, the pain alternates sides within a cycle. Even less common are patients in whom the pain of cluster occurs in the neck, the occiput, or other sites outside the trigeminal territory.[88] [112] The pain typically is described as boring or stabbing and has been likened to a hot poker in the eye. The onset of pain usually is rapid, peaking within 5 to 10 minutes. Although migraine sufferers prefer to lie in a darkened, quiet room, sufferers of cluster headache are restless; lying down often exacerbates the pain. Commonly, patients pace to and fro during an attack, sit upright in a chair holding their heads in their hands, or bang their heads against a wall. The pain paroxysms are so severe that many patients are driven to desperate measures, including suicide. During acute attacks of pain, sufferers experience one or more autonomic features ipsilateral to the headache. These autonomic signs and symptoms include ptosis (droopy eyelid), eyelid edema (swollen eyelid), miosis (constricted pupil), lacrimation (teary eye), conjunctival injection (bloodshot eye), forehead and facial sweating, nasal congestion, and rhinorrhea (runny nose). These accompanying features are brief, lasting only for the duration of the acute pain. Rarely a partial Horner syndrome (ptosis and miosis) may persist between attacks. Patients with typical cluster headaches preceded by visual auras have been described.[90]
Treatment

The treatment of cluster headache consists of abortive and prophylactic treatments. Abortive agents are employed to shorten the individual attack, whereas preventive agents are used to shorten or abolish the cycles. Acute treatments include inhalation of 100% oxygen at 8 to 10 L/min for 10 to 15 minutes through a nonrebreathing facemask; sumatriptan, 6 mg subcutaneous injections or 20 mg intranasally; and intravenous, intramuscular, or subcutaneous injections of dihydroergotamine, 0.5 to 1.0 mg, at headache onset.

Prophylactic medications useful in preventing attacks during cluster cycles include verapamil, sodium valproate, lithium carbonate, methysergide, and ergotamine tartrate. For refractory patients, a combination of two or more drugs may be required. The general principles guiding the use of these agents for cluster suggest that the medications be initiated early in the cluster period, then continued for approximately 2 weeks longer than the typical cycle, at which point they should be tapered gradually. Because a period of 2 weeks usually is required for most of these agents to take effect, often they are begun simultaneously with a prednisone taper, beginning at 60 mg/d, then tapered slowly during 10 to 14 days. Prednisone is helpful in that it rapidly induces a headache remission and keeps the patient headache-free, usually within 1 to 2 days.

Verapamil is the preventive medication of choice for the episodic and chronic forms of the disorder. Typical doses range from 120 to 480 mg daily, although higher doses occasionally are employed, particularly in chronic cluster headache. Verapamil may be combined with ergotamine, lithium, sodium valproate, or methysergide.

Sodium valproate has been reported to be effective in an open study in the management of cluster headache in doses ranging from 250 to 1000 mg daily.[41] Liver function and platelets should be monitored before initiating therapy and periodically during the course of treatment.

Ergotamine tartrate, 3 to 4 mg/d in divided doses, occasionally is useful in the treatment of these headaches. Ergotamine taken before bedtime usually prevents nighttime attacks. The concurrent use of sumatriptan and dihydroergotamine is contraindicated.

Lithium carbonate, 300 mg twice a day, is more effective for the treatment of chronic than episodic cluster headache.[53] Lithium levels should be maintained between 0.4 and 0.8 mEq/L.

Methysergide is effective in approximately 65% of patients with episodic cluster,[16] but because of the potential for fibrotic complications, it should not be used for longer than 6 months at a time. The daily dose is usually 2 mg 3 times a day, but higher doses occasionally are needed. The medication should not be used routinely with ergotamine tartrate, dihydroergotamine, or sumatriptan.
Headaches Sharing Some Clinical Features With Cluster Headache

The cluster headache variants discussed in this article consist of a diverse group of relatively uncommon headache disorders. Some of these headaches differ from cluster headache primarily in their frequency, duration, or treatment response. These disorders consist of paroxysmal hemicranias, hemicrania continua (HC), and SUNCT syndrome (short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing). A different group of cluster variants is characterized by their clinical presentations, which share features of cluster headache and another primary headache disorder, the cluster-tic and cluster-migraine syndromes. The hypnic headache syndrome does not share the cranial autonomic features of cluster headache, but because it may be misdiagnosed as cluster resulting from the pattern of short-lived nocturnal attacks it also is described in this article.


PAROXYSMAL HEMICRANIAS

The paroxysmal hemicranias are a group of rare, benign headache disorders that clinically resemble cluster headache, fail to remit with standard anticluster therapies, and respond spectacularly to indomethacin. Chronic paroxysmal hemicrania (CPH) first was described in 1974,[99] was named in 1976,[100] and appears in the IHS classification.[40] The first cases of CPH were characterized by multiple, short-lived, unilateral attacks that occurred on a daily basis for years without remission.[2] [86] [93] [99] [100] [106] [113] With time, it became clear that not all patients experienced this chronic unremitting course; some patients reported a remitting pattern with discrete headache phases separated by prolonged periods of pain-free remissions.[5] [7] [15] [30] [32] [48] [61] [67] [113] [114] Kudrow et al[48] named this pattern episodic paroxysmal hemicrania (EPH). Other patients have experienced an initially episodic course that over time evolved into the chronic nonrelenting phase.[2] [25]

The nomenclature for the various forms of the paroxysmal hemicranias has been controversial. The IHS recognizes only CPH. One nomenclature system uses CPH for the entire category and subclassifies the following forms: (1) chronic from onset, (2) chronic evolved from the remitting form, and (3) nonchronic/remitting.[2] The authors prefer CPH, EPH, and CPH evolved from EPH to describe these various syndromes.[5] [48] [61] [63] These terms are useful in that they are analogous to the IHS nomenclature of cluster headache. Proposed changes to the IHS classification system regarding the paroxysmal hemicranias are listed in the accompanying box.

Epidemiology

There have been more than 100 published case reports of paroxysmal hemicranias. Initially, these disorders were believed to be rare; however, the number of diagnosed cases is surely much higher because these disorders no longer are considered uncommon enough to warrant publication. Clinically, it appears that CPH is more common than EPH; only 19 well-documented cases of EPH appear in English publications.[24] [32] [67]

In contrast to cluster headache, CPH shows a female preponderance, with a sex ratio of approximately 2:1, whereas there is no gender preference noted for EPH. The age of onset ranges from 3 to 81 years, with a mean of approximately 33 years.[2] [10] [35] [46] [98] No family history of CPH or EPH was found in any of the reported cases. A documented family history of migraine was evident in 21% of reported cases,[63] whereas only one prior report documented a positive family history of cluster headaches.[2]
Clinical Features

Because the clinical profiles of EPH and CPH are essentially identical, these entities are discussed together. The pain is strictly unilateral and without side-shift in most sufferers. Bilateral pain was reported in one patient,[83] and in three patients, the headache showed side-shift.[2] The maximal pain is experienced in the ocular, temporal, maxillary, and frontal regions; nuchal and retro-orbital pain has been described less often. At times, the pain has been reported to radiate into the ipsilateral shoulder and arm. Strictly occipital pain has been reported in single reports of CPH[91] and EPH.[24] Rarely, toothache or otalgia is the presenting symptom.[6] [21]

The pain usually is characterized as a throbbing, boring, pulsatile, or stabbing sensation that ranges from moderate to excruciating in severity. Occasionally a mild discomfort at the usual site of pain is present interictally.[2] During acute attacks, sufferers usually prefer to sit quietly or lie in bed in the fetal position[115] ; only in rare reports do the patients assume the pacing activity usually seen in cluster.

In CPH, attacks recur 1 to 40 times daily. Most patients experience 15 or more attacks per day.[35] [63] [98] There is, however, a marked variability in attack frequency. Mild attacks recur 2 to 14 times daily; severe attacks recur 6 to 40 times daily.[63] Individual headaches usually last 2 to 25 minutes (range, 2 to 120 minutes).[7] [35] [63] [86] [93] In EPH, the daily attack frequency is 2 to 30 times, with attacks lasting 3 to 30 minutes each. The headache phase lasts 2 weeks to 4.5 months; remissions last 1 to 36 months.[24] [61] [63] [67] As with cluster headaches, attacks of CPH and EPH recur throughout the day and night; nocturnal attacks have been reported to occur in association with rapid eye movement (REM) sleep.[45] [67] [86] [98] [100]

Attacks may be triggered by bending or rotating the head,[2] [103] pressing on the transverse process of C4-5, C2 root, or greater occipital nerve.[102] [104] During acute attacks, one or more ipsilateral autonomic symptoms usually are present. Approximately 60% of sufferers report ipsilateral lacrimation. Homolateral ptosis (33%), conjunctival injection (36%), nasal congestion (42%), and rhinorrhea (36%) may accompany the headaches,[2] [35] [93] and ipsilateral miosis has been reported occasionally. [26] [82] Increased forehead sweating has been reported to occur in some patients on the symptomatic side during acute headache episodes, as has generalized sweating.[94] [104] In contrast to cluster headache, Horner's syndrome does not appear to accompany attacks of CPH or EPH.[23] [91] [92] Although the IHS criteria require at least one ipsilateral autonomic feature during attacks, patients with otherwise typical CPH without autonomic symptoms have been described.[8] [68] CPH has been reported to occur in association with other primary headache disorders, such as migraine,[73] cluster headache, [13] [43] [79] [117] and trigeminal neuralgia.[12] [36] [121] CPH is recognized in children.

Cases of symptomatic paroxysmal hemicrania have been reported as well. Disorders that have mimicked paroxysmal hemicranias include aneurysms within the circle of Willis[57] ; arteriovenous malformations and cerebrovascular accidents[10] [62] ; collagen vascular disease[57] ; Pancoast tumor[22] ; tumors of the frontal lobe, [57] sella turcica,[29] [118] and cavernous sinus[108] ; intracranial hypertension[39] ; and thrombocythemia. [50] A single posttraumatic case of CPH with typical migrainous aura has been described.[54]
Treatment

Indomethacin is the treatment of choice for paroxysmal hemicranias and has been deemed the sine qua non for establishing the diagnosis. Therapy usually is initiated at a dose of 25 mg 3 times a day and increased to 50 mg 3 times a day in 1 week if there is no response or only partial benefit. Headache resolution usually is prompt, occurring 1 to 2 days after the effective dose has been established, although it may take 2 weeks. Maintenance with doses ranging from 25 to 100 mg daily usually suffices; however, at times doses of 300 mg/d are required.

Dosage adjustments occasionally are necessary to treat the clinical fluctuations that sometimes are seen in these disorders; nighttime dosing with sustained-release indomethacin often prevents nocturnal exacerbations. During the active headache cycle, patients report that skipping or delaying doses of indomethacin may result in the prompt re-emergence of headaches. In patients suffering from EPH, indomethacin is given for slightly longer than the usual headache period, then tapered gradually. In patients with CPH, long-term treatment usually is required, although long-lasting remissions have been reported after cessation of indomethacin in rare patients with CPH.[95]

Patients requiring continuous, high dosages of indomethacin may have underlying pathology and need careful diagnostic evaluation.[108] Gastrointestinal side effects secondary to indomethacin may be treated with antacids, misoprostol, or histamine H2 receptor antagonists, and these agents always should be considered for patients who require long-term treatment.

Although the IHS criteria require indomethacin response as a diagnostic criterion, other agents have been reported to be of some benefit. Acetylsalicylic acid has been shown to be efficacious during the early phases of CPH in some patients[2] and possibly during the childhood phase of the disorder.[46] Partial success has been reported with verapamil,[14] [89] steroids,[37] and naproxen.[2] A piroxicam derivative was reported to be efficacious in some patients with CPH who also were responsive to indomethacin therapy,[97] and acetazolamide therapy successfully treated a patient previously unresponsive to indomethacin.[119] Sumatriptan has been reported to be beneficial in a patient suffering from bilateral CPH,[39] although its usefulness in the typical unilateral cases has not been shown.[17] [32] Successful treatment with the cyclooxygenase 2 inhibitor celecoxib was reported.[55] In patients refractory to indomethacin therapy, the diagnosis should be reconsidered.


HEMICRANIA CONTINUA

HC is another rare primary headache syndrome that responds to treatment with indomethacin. The disorder initially was described by Sjaastad and Spierings[107] in two patients with continuous headaches from onset. Subsequent reports described patients in whom episodes of prolonged pain were separated by pain-free remissions.[44] [64] [72] [109] In some patients, an initially episodic course evolved into the continuous form. As with paroxysmal hemicrania, the nomenclature for HC is controversial. Sjaastad and Antonaci[96] proposed that the classification of HC should be separated into remitting and unremitting forms. The unremitting form may be subclassified further as unremitting from onset and unremitting evolved from remitting. The authors have proposed nomenclature analogous to cluster headache: a remitting form with distinct headache phases separated by pain-free remissions, an unremitting form that evolved from the remitting form, and an unremitting form with continuous headache persisting for years.[32] [64] HC is not included currently in the IHS classification scheme. Proposed criteria are listed in Box 1.
Epidemiology

HC, similar to paroxysmal hemicrania, is probably an under recognized disorder. In headache subspecialty practices, HC is a common cause of refractory, unilateral, chronic daily headache. The disorder shows a marked female preponderance, with a female-to-male ratio of approximately 2:1. The age of onset ranges from 11 to 58 years (mean, 34 years).
Clinical Features

Most patients describe strictly unilateral pain, without side-shift. Two patients reported bilateral radiation of predominantly unilateral pain; one patient described bilateral pain; and in one patient with the remitting form, the pain alternated sides from attack phase to attack phase. The maximal pain is experienced in the ocular, temporal, and maxillary regions. Occasionally the pain may radiate into the ipsilateral occiput, nuchal, and retro-orbital areas.

The pain usually is described as a steady ache or throbbing pain. Superimposed on the continuous baseline low-level discomfort, most patients report exacerbations of more intense pain lasting 20 minutes to several days. Although significantly more intense than the usual background discomfort, the painful exacerbations never reach the level experienced by cluster headache sufferers. These exacerbations may occur at any time of the day or night and frequently awaken the patient from sleep. Exacerbations of pain often are accompanied by nausea; photophobia; and the autonomic features of cluster headache, including ipsilateral ptosis, conjunctival injection, lacrimation, and nasal congestion. When present, these associated features usually are much less pronounced than when seen in cluster headaches. Painful exacerbations are associated with a sensation of ocular discomfort, often likened to a foreign body in the eye (typically reported as sand or hair). Concurrent idiopathic (primary) stabbing headaches (jabs and jolts) are reported by many patients, occasionally occurring only in association with the painful exacerbations. During exacerbations of pain, patients assume the pacing activity usually seen with cluster headaches.

Although it is not a true cluster variant, HC may be mistaken for cluster if the physician focuses on the painful flare-ups with associated autonomic features. A careful history should reveal the presence of the continuous, low-level baseline discomfort in addition to the more disabling exacerbations. The autonomic features of HC, when present, tend to be much less pronounced than those of cluster.

Organic mimics of HC have been reported to occur in association with a mesenchymal tumor involving the sphenoid bone, clinoid process, and skull base.[32] Rarely the diagnosis of HC is masked by a concurrent medication rebound headache. In these instances, discontinuation of the overused analgesic is not associated with headache cessation, and the diagnosis of HC is made by exclusion.[120]
Treatment

Similar to paroxysmal hemicrania, HC is responsive to indomethacin. The treatment strategies detailed in the preceding section apply to this disorder as well. Other agents that may have partial success in the treatment of HC include naproxen and paracetamol, paracetamol in combination with caffeine, ibuprofen, piroxicam, and rofecoxib.[32] [80] Kuritzky[49] reported four patients who met the clinical criteria for HC but failed to respond to treatment with indomethacin or other agents. Kuritzky[49] termed this condition indomethacin-resistant HC.


SUNCT SYNDROME

The SUNCT syndrome is one of the rarest of the unusual primary headache disorders and has the most dramatic and variable clinical presentation. The syndrome first was described in 1978 and characterized more fully in 1989.[101] [105] Currently, 26 sufferers have been reported. The disorder has a male predominance (18 men, 8 women) with a sex ratio of 2.25:1.[4] [9] [32] [56] [76] [77] [84] Suggested clinical criteria for the diagnosis of SUNCT syndrome are listed in the accompanying box.

Clinical Features

SUNCT syndrome is characterized by brief headache episodes that recur multiple times per day. The age of onset ranges from 23 to 77 years (mean, 51 years).[77] The pain usually is maximal in the orbital and periorbital regions and may radiate to the ipsilateral forehead, temple, nose, cheek, and palate.[77] Attacks typically are unilateral; in three patients, however, pain was experienced simultaneously on the opposite side.[77] The pain quality usually is described as burning, stabbing, or electric-like. Paroxysms begin and end abruptly, reaching maximum intensity within 2 to 3 seconds.[77] Individual headache attacks last 5 to 250 seconds each (mean, 49 seconds),[75] although attacks lasting 2 hours each have been described.[70] Some patients describe a dull interictal discomfort that persists between acute episodes,[70] although most patients report being totally pain-free between attacks. Four patients experienced a status like pattern, in which painful paroxysms persisted 1 to 3 days.[69]

The temporal pattern is quite variable, with symptomatic periods alternating with periods of pain-free remissions occurring in an erratic fashion. Symptomatic periods generally last a few days to several months and occur once or twice yearly. Remissions range from 1 week to 7 years but usually are of a few months' duration.[77] During the symptomatic phase, daily attacks recur 6 to 77 times (mean, 28 times) [75] ; however, tremendous variability occurs among different patients and within the same patient. Attacks may be as infrequent as once per day or less to more than 30 attacks per hour.[75] [77] In one patient, attacks recurred in a repetitive and overlapping fashion for 1 to 3 hours at a time, twice daily.[74] Although attacks recur throughout the day, a bimodal distribution with increased attack frequency occurring in the morning and afternoon and evening hours has been described.[75] Nocturnal attacks were experienced by 12 patients.[77]

The acute attacks of headache in SUNCT syndrome are accompanied by a variety of associated symptoms, the most prominent of which are ipsilateral conjunctival injection and lacrimation. Ipsilateral nasal congestion, rhinorrhea, and eyelid edema are reported less commonly. In some patients, the accompanying autonomic phenomena were bilateral, although more pronounced on the side of the headache.[77] The associated tearing and conjunctival injection usually begin 1 to 2 seconds after the acute episodes of pain and may persist for a few seconds longer than the painful episodes.[77] In two patients, the associated symptoms remained 30 to 60 seconds after headache resolution,[3] [105] and in one patient, eyelid edema persisted for 5 to 10 minutes.[38] Rhinorrhea, when present, is delayed, occurring relatively late during the course of the headache.[77]

Many patients can precipitate acute attacks by touching certain trigger zones within the territory of V1-3. Other precipitating maneuvers include touching the hair, forehead, face, nose, and lip on the symptomatic side. Washing, shaving, eating, chewing, tooth brushing, talking, and coughing were reported as headache triggers.[77] Mechanical movements of the neck can precipitate attacks, although some patients could lessen or abort attacks by rotating their neck continuously.[77] [105] In contrast to trigeminal neuralgia, most patients have no refractory period. Secondary causes of SUNCT syndrome have been reported in four patients and include homolateral cerebellopontine angle arteriovenous malformations,[11] [20] brainstem cavernous hemangioma,[59] and a posterior fossa lesion in a patient with acquired immunodeficiency syndrome.[32]
Treatment

SUNCT syndrome has proved to be refractory to a variety of therapeutic approaches. Medications typically employed in the treatment of migraine, cluster, and other short-lived headache syndromes are ineffectual, as are anesthetic blockades.[71] Carbamazepine was reported to have a possibly beneficial effect in 5 of 18 patients.[77] Azathioprine, oral sumatriptan, prednisone, valproate, and nifedipine were shown to be mildly efficacious in single reports.[19] [31] [38] [71] Lamotrigine has been reported to abolish the syndrome and may be the treatment of choice.[19] Verapamil and omeprazole were reported to worsen the condition.[71]


CLUSTER-MIGRAINE AND CLUSTER-TIC SYNDROMES

Occasionally, patients describe headaches that have the features of cluster headache and another primary headache disorder. Recognition of these syndromes is important because the therapeutic options are different from the standard treatment of the separate disorders.

The cluster-migraine syndrome is diagnosed when elements of migraine headache occur simultaneously in patients suffering with cluster headache. Solomon and Kappa[111] instituted arbitrary diagnostic criteria to establish the diagnosis of this uncommon syndrome. According to their criteria, the diagnosis of cluster-migraine syndrome was given to patients who had symptoms of one headache predominantly (either migraine or cluster), but in whom four or five features of the other headache also were present. Patients who experienced cluster headache with nausea, vomiting, photophobia, or phonophobia would receive this diagnosis, as would patients with migraine who experienced ipsilateral autonomic features. The criteria employed by Solomon and Kappa[111] were not precise; the required number of associated symptoms was picked arbitrarily. Other clinicians have reported patients with two distinct headache disorders. Graham[34] described patients who suffered from recurrent bouts of migraine headaches that recurred daily for days or weeks at a time, then entered a period of pain-free remissions. It is important to recognize the cluster-migraine syndrome because of the unique treatment strategies that need to be implemented. Patients suffering from this syndrome have been reported to respond to inhalation of 100% oxygen as an abortive strategy for acute attacks and lithium carbonate as prevention. This combination would not be expected to be helpful in patients suffering from typical migraine. Alternatively, beta-blockers occasionally may help in this syndrome, whereas these agents would not be useful in the treatment of cluster headaches.

The diagnosis of cluster-tic syndrome is given to patients in whom cluster headache and trigeminal neuralgia coexist.[1] [110] This rare condition is characterized by repetitive volleys of excruciating lancinating pains that usually are described with trigeminal neuralgia, but in this syndrome they occur superimposed on the typical features of cluster headache. These tic like pains commonly are precipitated by light cutaneous or mucous membrane stimulation as in typical trigeminal neuralgia. Concurrently the patient also suffers from the typical clinical features of cluster headache. Often the two pain syndromes occur independently of each other for months or years before their simultaneous occurrence. In general, the cluster-tic syndrome is difficult to treat and may require a combination of therapies. Carbamazepine has been reported to abolish the tic like pains, whereas standard anticluster agents are required to treat the features of cluster. Solomon et al[110] described four patients with this syndrome who underwent microvascular decompression of the trigeminal nerve; compression of the root entry zone by a blood vessel was noted in all four patients. In two of the three patients in whom there was facial nerve exploration, an arterial loop was found at the root entry zone of the facial nerve. Postoperatively, all patients experienced relief of the neuralgia component of the syndrome; the features of cluster were not altered by the surgery, however.


HYPNIC HEADACHE SYNDROME

The hypnic headache syndrome is a rare primary headache disorder that first was described by Raskin in 1988,[85] then by Newman et al in 1990.[65] The initial description of the syndrome consisted of a bilateral, throbbing headache without associated autonomic features lasting 15 to 60 minutes, recurring one to three times nightly, often during REM sleep. At the time of this writing, 37 patients with the disorder have been described. The disorder has a female predominance (26 women, 11 men), with a sex ratio of 2.36:1.[25] [32] [33] [42] [60] [65] [66] [81] [85] Although most patients are elderly, the age of onset ranges from 40 to 82 years (mean, 66 years; median, 66 years). Headaches occur at a consistent time each night, usually between 1:00 and 3:00 A.M., and rarely may occur during a daytime nap.[25] The headaches begin abruptly, are diffuse and throbbing, and spontaneously resolve in 15 to 180 minutes. In 10 patients (27%), the headache was hemicranial.[25] [33] [42] [60] No associated autonomic symptoms accompany the pain, but nausea, photophobia, and phonophobia rarely may be present.
Treatment

All patients have been treated successfully with bedtime doses of lithium carbonate, 300 to 600 mg, although many patients could not tolerate the side effects. Bedtime doses of caffeine (5 patients); flunarizine (2 patients); indomethacin (1 patient); atenolol (1 patient); and combination of ergotamine tartrate, belladonna, and caffeine (1 patient) have been reported to treat this syndrome (Morales-Asin et al, 1998; Dodick et al, 1998; Ivanez et al, 1998). One patient treated with prednisone, vincristine, and cyclophosphamide for an unrelated illness experienced headache resolution (Newman et al, 1991). The accompanying box lists suggested criteria for hypnic headache.

SUMMARY

The disorders described in this article are relatively rare, but probably are more common than previously thought. Because these disorders cause significant pain and disability and treatment response differs from that of migraine, tension-type, and cluster headaches, recognition is essential. Table 1 lists the important clinical features of these syndromes and contrasts them with cluster headache, the disorder for which they are often confused.

TABLE 1 -- CLINICAL FEATURES

SUNCT = Short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing.

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*Addendum: These criteria were proposed before the reports of 10 patients with unilateral hypnic headaches.

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