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Migraine and the Trigeminal Autonomic Cephalalgias
SUMMARY
Headache is a common human experience and provides a considerable clinical challenge when it occurs. This chapter covers the major disabling primary headaches: migraine and the trigeminal autonomic cephalalgias, including cluster headache and hemicrania continua. These disorders share the pathobiology of activation—or the perception of activation—of the pain-producing innervation of the cranial vessels: the trigeminovascular system. Their individual phenotypes seem to have a substantial inherited component, and the signs and symptoms are reflected pathophysiologically by, among other things, distinct patterns of brain dysfunction on functional imaging. Migraine is a disorder of sensory modulation that involves the brain stem aminergic centers, whereas cluster headache with its circannual and circadian rhythmicity involves pivotal changes in neurons in the region of the posterior hypothalamus. Paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, and hemicrania continua are the other trigeminal autonomic cephalalgias with unique phenotypes and pathophysiology. Optimal management of each of these syndromes involves explaining the biology to patients, who are then engaged in the therapeutic process. A careful history leads to a specific diagnosis and drives treatment.
Introduction
Headache is among the most common of human maladies and is underpinned by an exciting neurobiology. From a pain perspective, the primary headaches are remarkable disorders in which headache and its associated features are seen in the absence of any necessary exogenous cause. In many ways they are anything but typical pain problems. This chapter focuses on two broad groups of primary headaches—migraine and the trigeminal autonomic cephalalgias (TACs)—in effect, sections 1 and 3 of the second edition of the International Classification of Headache Disorders (ICHD-II) ( ). Section 2 , tension-type headache, the other major headache by prevalence, is dealt with in Chapter 59 . Hemicrania continua (HC) has been added to the TACs as is currently proposed by the relevant International Headache Society Working Party ( ) ( Table 58-1 ). Here, the basic anatomy and physiology of these headaches are described, followed by the clinical syndromes and their management strategies. Some aspects of this work has been covered elsewhere ( ; ).
Table 58-1
Primary Headache Disorders
| TYPE | ICHD-II DESIGNATION |
|---|---|
| 1. Migraine | 1.1 Migraine with aura 1.2 Migraine without aura |
| 2. Tension-type headache | |
| 3. Trigeminal autonomic cephalalgias | 3.1 Cluster headache 3.2 Paroxysmal hemicrania 3.3 SUNCT/SUNA 3.4(r) Hemicrania continua ∗ |
| 4. Other primary headaches |
SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms; SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing.
After Headache Classification Committee of the International Headache Society 2004 The International Classification of Headache Disorders (second edition). Cephalalgia 24:1–160.
∗ Currently classified in section 4 as 4.7 and proposed to be moved to section 3 (see text).
Anatomy and Pathophysiology of Headache
Neurovascular Headache—Physiology
The basic physiological principle with these disorders is involvement, either in fact or in perception, of the pain-producing innervation of the dura mater and its associated vasculature. Changes in these elements lead to neurally driven vascular effects (i.e., a neurovascular pathophysiology; ). This is to distinguish changes in blood flow as a result of the metabolic demands of neurons (i.e., vasoneuronal coupling; ). It is also essential to note that the principle of neurovascular activation is not exclusive to these headaches; indeed, it is clear that experimental cranial pain will induce vasodilation ( ). This reflex can be identified in cats ( ), monkeys ( ), and humans ( , ). The reflex is functionally arranged in the first, or ophthalmic, division of trigeminal activation and results in changes in flow in structures innervated by the first division, both in the face ( , ) and in the brain ( , ). What is abnormal in primary neurovascular headaches is the degree to which normal, probably protective reflexes are activated by pain or, more likely, by the perception of pain. Thus, the concept of a vascular headache, although it no doubt exists as evidenced by subjects reporting mild pain with the potent vasodilator nitroglycerin ( ), has as its implication that vascular changes primarily drive the syndrome; however, this is not supported by clinical or basic experimental observations.
Neurovascular Headache—Anatomy
In experimental animals, detailed anatomy of the connections of the pain-producing intracranial extracerebral vessels and the dura mater ( ) has built on the classic human observations ( ; ; ; ; ) that these structures—and not the brain—are responsible for generating pain from within the head. The following key structures are involved in the nociceptive process from the viewpoint of clinical manifestations ( Fig. 58-1 ):
-
The large intracranial vessels and dura mater
-
The peripheral terminals of the trigeminal nerve that innervate these structures
-
The central terminals and second-order neurons of the trigeminal nucleus
Together, these structures are known as the trigeminovascular system ( Table 58-2 ). The cranial parasympathetic autonomic innervation provides the basis for other symptoms, such as lacrimation and nasal stuffiness, that are prominent in the TACs (see Table 58-1 ), although they may also be seen with migraine. It is clear from human functional imaging studies that vascular changes in migraine and cluster headache (CH) are driven by these neural vasodilator systems, so these headaches should be regarded as neurovascular. The concept of a primary vascular headache should be consigned to the dustbin of history since it neither explains the pathogenesis of what are complex central nervous system disorders nor does it necessarily predict treatment outcomes.
Table 58-2
Anatomy of Primary Neurovascular Headaches
| STRUCTURE | COMMENTS | |
|---|---|---|
| Target Innervation | ||
| Cranial vessels, dura mater | Ophthalmic branch of the trigeminal nerve | |
| 1st | Trigeminal ganglion | Middle cranial fossa |
| 2nd | Trigeminal nucleus (quintothalamic tract) | Trigeminal nucleus caudalis and C1/C2 dorsal horns |
| 3rd | Thalamus | Ventrobasal complex Medial nucleus of the posterior group Intralaminar complex |
| Modulatory | Midbrain | Periaqueductal gray matter |
| Hypothalamus | To be determined | |
| Final | Cortex | Insulae Frontal cortex Anterior cingulate cortex Basal ganglia |
Neurovascular Headache—What Determines the Manifestations?
Even though these disorders share much in terms of anatomy and physiology, their clinical manifestations are rather distinct—what is the basis for this? To some extent the uniqueness of these disorders must be a consequence of their genetics and how it is manifested in the central nervous system.
Genetics
Migraine is an episodic syndrome of headache characterized by sensitivity to normal sensory input, such as to light, sound, and head movement, probably because of dysfunction of aminergic brain stem/diencephalic sensory control systems ( Fig. 58-2 ). The first of the migraine genes was identified for familial hemiplegic migraine (FHM), in which about 50% of families have mutations in the gene for the Ca v 2.1 subunit of the neuronal P/Q-type voltage-gated calcium channel ( ). Additional causes of FHM include mutations in ATP1A2 , which encodes the α 2 subunit of the Na + /K + pump ( ), and mutations in the voltage-gated sodium channel gene SCN1A ( ). Most recently, a genome-wide association study has implicated genes involved in glutamate homeostasis ( ), and the most recent candidate mutation in patients with sporadic hemiplegic migraine involves the glial glutamate transporter gene SLC1A3 ( ). These genetic findings suggest that migraine, or at least the aura, may be part of the spectrum of diseases known as channelopathies ( ). It is notable that the very strongest data remain for migraine with aura.
Brain Manifestations
Migraine aura is characterized by changes in cortical blood flow ( ) consistent with the animal experimental phenomenon of cortical spreading depression ( ). Functional neuroimaging has suggested that brain stem regions such as the dorsal midbrain ( ) and dorsolateral pons ( , , ) play a crucial role in migraine, at least during the attack proper. There may be hypothalamic changes ( ) more anterior than those seen with the TACs. Such data afford opportunities to understand migraine pathophysiology and provide targets for bench experimental studies. The TACs all share the common imaging finding of changes in the region at the most posterior portion of the hypothalamic gray matter, which may indeed be part of the hypothalamus or a structure just behind it; anatomical studies are needed. CH ( ), paroxysmal hemicrania (PH) ( ), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) ( ), and HC ( ) share this signature. These syndromes have additional changes that make their imaging signature unique ( ).
Migraine
Diagnosis of Migraine
Migraine is generally an episodic headache with certain associated features, such as sensitivity to light, sound, or movement, and nausea or vomiting often accompanies the headache ( Table 58-3 ). None of the features is compulsory, and indeed, given that migraine aura, or visual disturbances consisting of flashing lights or zigzag lines moving across the fields, or other neurological symptoms are reported in only about 20% of patients ( ), a high index of suspicion is required to diagnose migraine. A headache diary can often be helpful in making the diagnosis and perhaps more so in measuring the burden of the disease on the individual and then observing the effects of treatment ( ). In a minimalist diary patients would mark on a calendar each headache day, the length of the attack, what medication was taken and the doses, and what life events may have been taking place, such as a menstrual cycle.
Table 58-3
Simplified Diagnostic Criteria for Migraine
| Repeated attacks of headache lasting 4–72 hours that have the following features, normal findings on physical examination, and no other reasonable cause for the headache | |
|---|---|
| AT LEAST 2 OF | AT LEAST 1 OF |
|
|
After Diagnosis and management of migraine. British Medical Journal 312:1279–1282; adapted from The International Classification of Headache Disorders (second edition). Cephalalgia 24:1–160.
In differentiating the two main primary headache syndromes seen in clinical practice, migraine at its simplest level is headache with associated features, and tension-type headache is otherwise featureless headache; furthermore, most patients with disabling headaches seen by physicians probably have a migrainous biology. In terms of pragmatic clinical management, it is probably preferable to misdiagnose tension-type headache as migraine as opposed to the reverse since there is so much good that can be done for migraine sufferers and such a paucity of therapeutic strategies for tension-type headache; patients have little to lose by such a bias. If headache with associated features describes migraine attacks, headachy describes migraine sufferers over their lifetime. Migraine sufferers inherit a tendency to have their headache amplified at various times by interaction with the environment: triggers. The brain of a migraineur seems to be more sensitive to sensory stimuli and to change, and this tendency is often amplified in females during their reproductive years. Migraine sufferers do not habituate to sensory stimuli easily and thus can be unfairly and frequently stimulated in the world in which they live and work. Migraine sufferers may have headaches when they sleep in, when they are tired, when they skip meals, when they have stress, or when they relax. They are less tolerant of change, and part of successful management is to advise them to maintain regularity in their lives in the knowledge of this fluctuating biology.
Chronic Migraine
One of the most vexing questions in migraine has been the upper frequency of attacks, the simple question of whether migraine can occur daily or nearly daily. The revised International Headache Society classification specified chronic migraine as being essentially 15 days or more per month of headache, with at least 15 days fulfilling the criteria for migraine without aura ( ), and this has been modified somewhat to allow for treated days ( ). It seems illogical to suppose that the transition between 14 days of migraine per month and 16 days per month has any particular biological significance, and it is more likely that the range lies on a spectrum ( ). The term chronic daily headache (CDH) is an umbrella expression that says no more than that patients have headaches 15 days or more per month and begs the clinical question of what the underlying biology or pathology is. CDH is not a diagnosis but a “parking lot” in which to hold the patient until the diagnosis is made.
It is remarkable that patients with throbbing exacerbations of tension-type headache have raised levels of calcitonin gene–related peptide ( ), just as seen with migraine ( , , ). They share patterns of triggering by alcohol ( ) with migraine sufferers ( ) if they have a family history of migraine or a personal history of the disorder. Moreover, tension-type headache in migraine sufferers responds to triptans, whereas they do not help non-migraineurs ( ). Finally, episodic ( ) and chronic ( ) migraine sufferers share the same area of activation in the dorsolateral pons on functional brain imaging. In essence, the question seems to be why some migraineurs pass through a period of frequent headaches and some do not. It may relate to medication misuse, although this is clearly not the entire answer ( ).
Disability Assessment
After making a diagnosis the second step in the clinical process is to be sure that the disease burden has been captured ( ): how much headache patients have and, more important, what their degree of disability is. One can ask the patient directly to get an idea, request that the patient keep a diary, or obtain a quick but accurate estimate with the Migraine Disability Assessment Scale (MIDAS; Fig. 58-3 ), which is well validated and very easy to use in practice ( ). As an alternative or indeed in addition, one can use the Headache Impact Test (HIT-6) ( ). Incorporation of disability assessment, whether it is an informal quiz of patients that permits some understanding of how the disorder affects them or whether it is determined with the MIDAS tool, genuinely improves the clinical interaction and affects management decisions ( , ). Moreover, assessment of disability allows physicians to be familiar with the broader societal effects of migraine ( ).
Management of Migraine
After diagnosis, management of migraine begins by explaining certain things to the patient ( ), notably the following:
-
Migraine is an inherited tendency to have headaches and cannot be cured.
-
Migraine can be modified and controlled by adjustments in lifestyle and the use of medications.
-
Migraine is not life-threatening or associated with serious illness with the exception of females who smoke and are taking estrogenic oral contraceptives ( ); migraine can make life a misery.
-
Management of migraine takes time and co-operation; information, such as from a headache diary, has to be collected or inquiry made concerning the effect of the disease on the patient’s life—the disability accredited to the disease.
Non-pharmacological Management of Migraine
Put very simply, non-pharmacological management of migraine consisting of helping patients identify things that make the problem worse and encourage them to modify these factors. Many patients will not find any joy in this approach and should not be pilloried for this; however, for those who do identify such factors, it will be a rewarding strategy. The crucial lifestyle advice is to explain to patients that migraine is a state of brain sensitivity to change. This implies that migraine sufferers need to regulate their lives by eating a healthy diet, regularly performing exercise, maintaining consistent sleep patterns, avoiding excessive caffeine and alcohol, and as much as practical, modifying or minimizing changes in stress. A balanced life with fewer highs and lows will benefit most migraine sufferers. Patients also need to know that the brain sensitivity that defines migraine varies, so triggers will vary in their likelihood to result in headache.
Preventive Treatment of Migraine
The decision to start preventive treatment requires input from both the doctor and migraine sufferer. The basis for considering preventive treatment from a medical viewpoint is a combination of acute attack frequency and attack tractability. Patients with attacks unresponsive to medications for acute attacks are easily considered for prevention, whereas those with attacks that can be treated simply may be less obviously candidates. The other part of this equation relates to what is happening over time. If a patient’s diary shows a clear trend toward increased frequency, it is better to start prevention early than to wait for the problem to become more troublesome. A simple rule for frequency might be that for one to two headaches per month there is usually no need to start preventive treatment, for three to four episodes it may be needed but not necessarily, and for five or more per month, prevention should definitely be on the agenda for discussion. Options available for treatment are covered in detail in Table 58-4 and vary somewhat by country. The problem with preventives is not that there are none but that they have fallen into use for migraine from other indications and often have substantial side effect burdens. Frequently, the doses required to reduce headache frequency produce marked and intolerable side effects. It is not clear how preventives work, although it seems likely that they modify the brain sensitivity underlying migraine. Another key clinical point is that generally each drug should be started at a low dose and gradually increased to a reasonable maximum if there is going to be a clinical effect. Dose should be optimized for weight, and this is a good rule for both pediatric and adult practice.
Table 58-4
Preventive Treatment of Migraine ∗
| DRUG | DOSE | SELECTED SIDE EFFECTS |
|---|---|---|
| β-Blocker | ||
| Propranolol ( , , ) | 40–120 mg twice daily | Reduced energy, tiredness Postural symptoms Contraindicated with asthma |
| Metoprolol | 25–100 mg twice daily | Reduced energy, tiredness Postural symptoms Contraindicated with asthma |
| Anticonvulsants | ||
| Valproate ( , , ) | 400–600 mg twice daily | Drowsiness Weight gain Tremor Hair loss Fetal abnormalities Hematological or liver abnormalities |
| Topiramate ( , , ) | 50–200 mg/day | Paresthesias Cognitive dysfunction Weight loss Care with a family history of glaucoma Nephrolithiasis |
| Gabapentin ( ) † | 900–3600 mg daily | Dizziness Sedation |
| Flunarizine ( , ) | 5–15 mg daily | Drowsiness Weight gain Depression Parkinsonism |
| Antidepressants | ||
| Amitriptyline ‡ ( ) Dosulepin (dothiepin) Nortriptyline |
25–75 mg nocte | Drowsiness, urinary retention, arrhythmias Note : some patients are very sensitive and may need a total dose of only 10 mg, although generally 1–1.5 mg/kg body weight is required |
| Venlafaxine ( , ) | 75–150 mg daily | Drowsiness Urinary retention Arrhythmias |
| Serotonin Antagonists | ||
| Pizotifen ( ) | 0.5–2 mg daily | Weight gain Drowsiness |
| Methysergide ( ) | 1–6 mg daily | Drowsiness Leg cramps Hair loss Retroperitoneal fibrosis (1-mo drug holiday required every 6 mo) |
| Single Studies § | ||
| Lisinopril ( ) | 20 mg daily | Cough |
| Candesartan ( ) | 16 mg daily | Dizziness |
| Nutraceuticals ¶ | ||
| Riboflavin ( ) | 400 mg daily | |
| Coenzyme Q 10 ( ) | 100 mg three times daily or 75 mg twice daily | |
| Butterbur ( ) | 50–75 mg twice daily | Gastrointestinal upset |
| Feverfew ( , , , , ) | 6.25 mg three times daily | Elevation of transaminases Rash |
| No Convincing Controlled Evidence | ||
| Verapamil ( , , ) | ||
| Controlled Trials Demonstrate No Effect | ||
| Nimodipine ( ) | ||
| Clonidine ( ) | ||
| Selective serotonin reuptake inhibitors: fluoxetine ( ) | ||
∗ Commonly used preventives are listed with reasonable doses and common side effects. The local national formulary should be consulted for detailed information.
† More supported by experience because the single cited study did not achieve the primary end point on an intention-to-treat basis.
‡ A small study, although a very widely used treatment.
§ Compounds not widely considered mainstream but with a positive randomized controlled trial versus placebo.
¶ Non-pharmaceuticals with at least one positive randomized controlled trial versus placebo.
Therapies for Acute Attacks of Migraine
Acute attack therapies for migraine can be usefully divided into disease–non-specific treatments, analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), and disease-specific treatments, ergot-related compounds and triptans ( Table 58-5 ). It must be said at the outset that most acute attack medications seem to have a propensity to aggravate headache frequency and induce a state of refractory daily or nearly daily headache: CDH with medical misuse. This may be related to the fact that most of the medications are receptor agonists. Codeine-containing compound analgesics are a particularly pernicious problem when available in over-the-counter preparations, and it is generally advised that patients avoid frequent use, more than six times per month. Many patients who stop taking regular analgesics will have no change in their headache, but most in some way feel better and will be easier to treat with standard preventives.
Table 58-5
Oral Acute Migraine Treatments
| NON-SPECIFIC TREATMENTS ∗ | SPECIFIC TREATMENTS |
|---|---|
| Aspirin (900 mg) Acetaminophen (paracetamol, 1000 mg) NSAIDs:
|
Ergot derivatives:
Triptans:
|
∗ Often used with antiemetic/prokinetics, such as domperidone (10 mg) or metoclopramide (10 mg).
Treatment Strategies
Given the array of options to control an acute attack of migraine, how does one start? The simplest approach to treatment has been described as stepped care . In this model all patients are treated, assuming no contraindications, with the simplest treatment, such as aspirin, 900 mg, along with an antiemetic. Aspirin is an effective strategy, has been proved so by double-blind controlled clinical trials, and is best used in its most soluble formulation. The alternative would be a strategy known as stratified care , in which the physician determines, or stratifies, treatment at the start based on likelihood of response to levels of care. An intermediate option may be described as stratified care by attack. The latter is what many headache authorities suggest and what patients often do when they have the option. Patients use simpler options for less severe attacks and rely on more potent options when their attacks or circumstances demand them ( Table 58-6 ).
Table 58-6
Clinical Stratification of Acute Specific Migraine Treatments
| CLINICAL SITUATION | TREATMENT OPTIONS |
|---|---|
| Failed analgesics/non-steroidal anti-inflammatory drugs | First tier:
Slower effect/better tolerability:
Infrequent headache:
|
| Early nausea or difficulty taking tablets | Sumatriptan, 20 mg nasal spray Zolmitriptan, 5 mg nasal spray Rizatriptan, 10 mg MLT wafer Zolmitriptan, 2.5 mg dispersible |
| Headache recurrence | Ergotamine, 2 mg (perhaps most effective PR/usually with caffeine) Naratriptan, 2.5 mg PO Eletriptan, 80 mg |
| Tolerating acute treatments poorly | Naratriptan, 2.5 mg Frovatriptan, 2.5 mg |
| Early vomiting | Sumatriptan, 25 mg PR Sumatriptan, 6 mg SC |
| Menstrually related headache | Prevention:
Treatment:
|
| Very rapidly developing symptoms | Sumatriptan, 6 mg SC Dihydroergotamine, 1 mg IM |
IM, intramuscularly; MLT, xxx; PO, orally; PR, per rectum; SC, subcutaneously.
Treatment of Non-specific Acute Attacks
Simple things, such as aspirin and acetaminophen (paracetamol), are cheap, can be very effective, and can be used by many patients. Dosages should be adequate, and the addition of domperidone (10 mg orally), metoclopramide (10 mg orally), promethazine (25 mg) if sedation is helpful, or ondansetron (4–8 mg) can be very helpful. NSAIDs can be very useful when tolerated. Their success is often limited by inappropriate dosing, and adequate doses of naproxen (500–1000 mg orally or rectally with an antiemetic), ibuprofen (400–800 mg orally), or tolfenamic acid (200 mg orally) can be extremely effective. Tolfenamic acid has been shown in a double-blind placebo-controlled study to have comparable efficacy to sumatriptan, 100 mg, a result that reinforces the general clinical view that NSAIDs can be very useful compounds in patients with migraine.
Specific Treatment of Acute Attacks
When simple measures fail or more aggressive treatment is required, specific treatments are required. Although ergotamine remains an option, its place as the first choice is no longer widespread ( ). In particular situations ergotamine is very useful, but its use must be carefully monitored because overuse of ergotamine produces dreadful headache in addition to a host of vascular problems. The triptans have revolutionized the life of many patients with migraine and are clearly the most powerful option available to stop a migraine attack. They can be rationally applied (see Table 58-6 ) by considering their pharmacological, physicochemical, and pharmacokinetic features ( ), as well as the formulations that are available ( ).
Trigeminal Autonomic Cephalalgias
The TACs are a group of primary headache disorders characterized by unilateral pain in the trigeminal distribution that occurs in association with prominent ipsilateral cranial autonomic features ( ). These headaches will be grouped in section 3 of the revised International Headache Society classification ( ). The TACs include CH, PH, and SUNCT syndrome and should also include HC. Monographs that have strong historical relevance ( , ) have been written on these topics, and a number of monographs ( , , , ) and reviews ( ; , 2005) are available for further reading.
CH, PH, and SUNCT syndrome are characterized by short-lasting headaches with autonomic features. These syndromes differ in their attack duration and frequency, as well as in their response to therapy. CH has the longest attack duration and relatively low attack frequency. PH has intermediate duration and intermediate attack frequency. SUNCT syndrome has the shortest attack duration and the highest attack frequency ( Table 58-7 ). The importance of recognizing these syndromes relates to their excellent, highly selective response to treatment.
Table 58-7
Typical Clinical Features of Trigeminal Autonomic Cephalalgias, Including Hemicrania Continua
| CLUSTER HEADACHE | PAROXYSMAL HEMICRANIA | SUNCT SYNDROME | HEMICRANIA CONTINUA | |
|---|---|---|---|---|
| Sex F:M | 1:3.5–7 | 2.13–2.36:1 | 1:2.1 | 2.4:1 |
| Pain: | ||||
| Type | Stabbing, boring | Throbbing, boring, stabbing | Burning, stabbing, sharp | Background dull ache, throbbing/stabbing exacerbations |
| Severity | Excruciating | Excruciating | Severe | Moderate background pain; severe exacerbations |
| Site | Orbit, temple | Orbit, temple | Periorbital | Orbit, temple |
| Attack frequency | 1 every other day–8 daily | 1–40/day | 1/day–30/hr | Continuous |
| Duration of attack | 15–180 min | 2–45 min | 5–250 sec | Continuous background pain; exacerbations quite variable and lasting minutes to days |
| Autonomic features | Yes | Yes | Yes (prominent conjunctival injection and lacrimation) | Yes—mainly with exacerbations; less prominent than with other TACs |
| Migrainous features ∗ | Yes | Yes | Yes † | Yes—during exacerbations |
| Alcohol trigger | Yes | Occasional | No | Rare |
| Indomethacin effect | − | ++ | − | ++ |
| Abortive treatment | Sumatriptan injection or nasal spray Oxygen |
Nil | Nil | Nil |
| Prophylactic treatment | Verapamil Methysergide Lithium Prednisolone |
Indomethacin | Lamotrigine Topiramate Gabapentin |
Indomethacin |
TACs, trigeminal autonomic cephalalgias.
Cluster Headache
CH is a strictly unilateral headache that occurs in association with cranial autonomic features and, in most patients, has a striking circannual and circadian periodicity. It is an excruciating syndrome and is probably the most painful condition known to humans, with female patients describing each attack as being worse than childbirth. The prevalence of CH is estimated to be 0.1% ( , ), approximately the same as that of multiple sclerosis in the United Kingdom. The male-to-female ratio is 3.5–7:1 ( , ). The male-to-female ratio has changed in case series in the past 15 years, with a trend toward increasing female preponderance. It seems likely that this is an ascertainment issue, not a real shift in female incidence. CH can begin at any age, although the most common age at onset is the third or fourth decade of life.
Diagnosis of Cluster Headache
It may be useful to the reader to define the terminology used with CH. A cluster headache or attack is an individual episode of pain that can last from a few minutes to some hours. A cluster bout or period refers to the duration over which recurrent cluster attacks occur, usually some weeks or months. A remission is the pain-free period between two cluster bouts. Clinicians should be aware there are a number of secondary causes of cluster-like headaches ( Table 58-8 ), and brain imaging seems reasonable at the first diagnosis given that one is likely to manage such patients over their lifetime. In one study, about one-tenth of patients with episodic CH (see the later section Cluster Headache Bouts ) evolved into chronic CH, whereas one-third of patients with chronic CH transformed into episodic CH ( ). An encouraging piece of information for sufferers is that a substantial proportion of them can expect to have longer remission periods as they age ( ).
Table 58-8
Differential Diagnosis of Trigeminal Autonomic Cephalalgias
| PRIMARY TACs | SIMILAR SECONDARY HEADACHES | SECONDARY TCAs–CLUSTER-LIKE HEADACHES |
|---|---|---|
| Cluster headache Paroxysmal hemicrania SUNCT/SUNA syndrome |
Tolosa-Hunt syndrome Maxillary sinusitis Temporal arteritis Raeder’s paratrigeminal neuralgia ( ) Trigeminal neuralgia |
Vascular:
Tumors:
Infective:
Post-traumatic or after surgery:
Dental:
Miscellaneous:
|
AVM, arteriovenous malformation; SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic features; SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; TACs, trigeminal autonomic cephalalgias.
Cluster Headache Attacks
Attacks are strictly unilateral, with very few exceptions, although the headache may alternate between sides. The pain is excruciatingly severe. It is located mainly around the orbital and temporal regions, although any part of the head can be affected. The headache usually lasts 45–90 minutes; the ICHD-II criteria set the limit from 15 minutes to 3 hours ( Box 58-1 ). It has an abrupt onset and cessation. Interictal pain or discomfort is present in some patients ( ). A signature feature of CH is its prominent association with cranial autonomic symptoms. The ICHD-II ( ) requires the attacks to be accompanied by at least one of the following, which have to be present on the painful side: conjunctival injection, lacrimation, miosis, ptosis, eyelid edema, rhinorrhea, nasal blockage, forehead or facial sweating, or a sense of restlessness or agitation (see Box 58-1 ). The cranial autonomic features are transient and last only for the duration of the attack, with the exception of partial Horner’s syndrome; ptosis or miosis may rarely persist, especially after frequent attacks.
Box 58-1
Diagnostic Features of Cluster Headache
Modified from The International Classification of Headache Disorders (second edition). Cephalalgia 24:1–160.
-
Cluster headache has two key forms:
-
Episodic : occurs in periods lasting 7 days to 1 year separated by pain-free periods lasting 1 month or longer
-
Chronic : attacks occur for more than 1 year without remission or with remissions lasting less than 1 month
-
∗ Not attributable to another disorder.
Headaches must have each of the following:
-
Severe unilateral orbital, supraorbital, and/or temporal pain lasting 15–180 minutes untreated
-
Frequency of attacks: from 1 every other day to 8 per day
-
Headache associated with at least one of the following signs, which have to be present on the painful side:
-
Conjunctival injection
-
Lacrimation
-
Nasal congestion
-
Rhinorrhea
-
Forehead and facial sweating
-
Miosis
-
Ptosis
-
Eyelid edema
-
Sense of restlessness or agitation during headache
-
Typical migraine premonitory symptoms, such as tiredness and yawning ( ), and its associated features, including nausea, vomiting, photophobia, phonophobia, and aura, have all been described in relation to cluster attacks ( , , ). However, in contrast to migraine, CH sufferers are usually restless and irritable and prefer to move about while looking for a movement or posture that may relieve the pain ( ). Cluster attack frequency varies between one every alternate day to three daily, although some have up to eight daily. The condition can have a striking circadian rhythmicity, with some patients reporting that the attacks occur at the same time each day. Alcohol, nitroglycerin, exercise, and elevated environmental temperature are recognized precipitants of acute cluster attacks. Alcohol induces acute attacks, usually within an hour of intake, in the vast majority of sufferers, in contrast to migraine sufferers, who generally have headache some hours after alcohol intake. Alcohol triggers attacks during a cluster bout but not during a remission. Allergies, food sensitivities, reproductive hormonal changes ( ), and stress do not appear to have any significant role in precipitating attacks.
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