18.1 General principles [link]
18.2 Migraine [link]
18.3 Tension-type headache [link]
18.4 Trigeminal-autonomic cephalalgias [link]
18.5 Other primary headaches [link]
18.6 Chronic daily headache [link]
18.6.1 Range of conditions [link]
18.6.2 Chronic migraine [link]
18.6.3 Management [link]
18.6.4 Medication overuse [link]
18.6.5 Preventive treatments [link]
18.6.6 New daily persistent headache [link]
18.6.7 Low CSF volume headache [link]
18.6.8 Raised CSF pressure headache [link]
18.6.9 Post traumatic headache [link]
18.7 Other forms of secondary headache [link]
Migraine is an episodic brain disorder that affects about 15 per cent of the population (Lipton et al. 2001; Steiner et al. 2003), can be highly disabling (Menken et al. 2000), and has been estimated to be the most costly neurological disorder in the European Community at more than €27 billion per year (Andlin-Sobocki et al. 2005). It is the most common reason for neurological referral in the United Kingdom, estimated by the Association of British Neurologists to drive 20 per cent of referrals in outpatients; epilepsy is next at 12 per cent. Unfortunately, there is a tacit assumption that doctors in general just understand headache, and that neurologists in particular have special knowledge and training in the field. Sadly this is most often not the case and they learn on the job often perpetuating mistakes of their supervisors. To manage headache can be a source of extreme frustration or undiluted pleasure; the difference simply reflects how much one knows about the subject. Readers encouraged either by this text or by their clinical experience can look more deeply into headache with detailed texts (Goadsby and Silberstein 1997; Silberstein et al. 2002; Lance and Goadsby 2005; Olesen et al. 2005).
18.1 General principles
A formal nosology for headache disorders exists in the second edition of the International Classification of Headache Disorders (Headache Classification Committee of The International Headache Society 2004). This system will largely be employed here. There are many types of headache, and diagnosis is the key to proper management. The International Headache Society system is explicit, in the sense that it uses characteristic features of the headache to make the diagnosis, summing these features to make the diagnosis more certain. The general concept is that there are primary and secondary forms of headache, following the generic medical principle that clinical syndromes may be caused by something exogenous, secondary, or may manifest de novo as the primary disease process. Such a system is outlined in Table 18.1.
Table 18.1 Common causes of headache†
† after Olesen et al.(2005).
Broadly, primary headaches are those in which headache and its associated features are the disease in themselves, and secondary headaches are those caused exogenously, such as the headache commonly associated with fever. Mild secondary headache, such as that seen in association with upper respiratory tract infections is common but only rarely worrisome. The clinical dilemma remains that while life-threatening headache is relatively uncommon in the Western society, it occurs and its detection requires suitable vigilance by the doctors. Primary headache in contrast often confers considerable disability over time and while not life-threatening certainly robs patients of quality of life. Primary headache is a staple of the clinical neurologist’s diet.
18.1.1 Primary headache syndromes
The primary headaches are a group of fascinating disorders in which headache and associated features are seen in the absence of any exogenous cause. The common syndromes (Table 18.1) are tension-type headache, migraine, and cluster headache. The collection of headaches known as primary chronic daily headache form the greatest part of the neurologist’s burden. Some other less well-known, indeed rarer syndromes will be mentioned because they are easily treated when diagnosed.
18.1.2 Anatomy and physiology
The disabling primary headaches, migraine, and cluster headache, have been studied extensively in recent times and they are now relatively well-understood insofar as neurological disorders that involve the brain are concerned. In experimental animals the detailed anatomy of the connections of the pain-producing intracranial extracerebral vessels and the dura mater has been built on the classical human observations of Wolff and others. It is these structures, and not the brain itself, that are involved in head pain, although it is not at all clear to what extent there is nociceptive activation or the perception of that activation.
The key structures involved are:
♦ 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 caudal trigeminal nucleus and dorsal horns of C1 and C2, trigeminocervical complex;
♦ higher centre processing in the thalamus, ventroposteromedial and posterior thalamus, and cortex; and
♦ modulatory centres in the diencephalon and brainstem, such as periaqueductal grey matter, locus coeruleus, and parts of the hypothalamus.
The innervation of the large intracranial vessels and dura mater by the trigeminal nerve is known as the trigeminovascular system. The cranial parasympathetic autonomic innervation provides the basis for symptoms, such as lacrimation and nasal stuffiness, which are prominent in cluster headache and paroxysmal hemicrania, although they may also be seen in migraine. It is clear from human functional imaging studies that vascular changes in migraine and cluster headache are driven by these neural vasodilator systems so that these headaches should be regarded as neurovascular. The concept of a primary vascular headache should be abandoned since it neither explains the pathogenesis of what are complex central nervous system disorders, nor does it necessarily predict treatment outcomes. The term vascular headache has no place in modern neurological practice when referring to primary headache.
Migraine is an episodic syndrome of headache with sensory sensitivity, such as to light, sound, and head movement, probably due to dysfunction of aminergic brainstem/diencephalic sensory control systems (Fig. 18.1). The first of the migraine genes has been identified for familial hemiplegic migraine, and includes mutations in the CACNA1A gene for the CaV2.1 (α1A) subunit of the neuronal P/Q voltage-gated calcium channel, the Na/K ATP pump α2 subunit gene ATP1A2, and the voltage-gated sodium channel SCN1A. These findings and the clinical features of migraine suggest it might be part of the spectrum of diseases known as channelopathies, or now ionopathies, disorders involving dysfunction of ion channel fluxes. Functional neuroimaging has suggested that brainstem regions in migraine (Fig. 18.2), and the posterior hypothalamic grey matter site of the human circadian pacemaker cells of the suprachiasmatic nucleus, in cluster headache (Fig. 18.3), are good candidates for specific involvement in primary headache (Cohen and Goadsby 2006a).
18.1.3 Secondary headache
It is imperative to establish in the patient presenting with any form of head pain whether there is an important secondary headache that is declaring itself. The headaches of subarachnoid haemorrhage (Section 35.16.2), meningitis (Section 41.2.1), giant cell arteritis (Sections 18.7.1; 36.2.8), and raised intracranial pressure (Section 26.5), are important examples of medically sinister headaches. Perhaps the most crucial clinical feature to elicit is the length of the history. Patients with a short history require prompt attention and may require quick investigation and management. Patients with a longer history generally require time and patience rather than alacrity. There are some important general features, including associated fever or sudden onset of pain (Table 18.2); these demand attention. Patients with a history of recent onset headache or neurological signs need a positive diagnosis of a benign disorder or require brain imaging with CT or MRI. Patients with a history of recurrent headaches over a period of 1 year or more, fulfilling International Headache Society criteria for migraine (Table 18.3) and with a normal physical examination, have positive brain imaging in only about 1/1000 images. In general it should be noted that brain tumour is a rare cause of headache, and rarely a cause of isolated long-term histories of headache. A notable exception to the general rules about secondary headache is pituitary tumour, which can trigger underlying primary headache biologies, and should always be considered, especially in the differential diagnosis of trigeminal autonomic cephalalgias (Levy et al. 2005).
Table 18.2 Warning signs in head pain
♦ Sudden onset of pain
♦ Marked change in pain character or timing
♦ Neck stiffness
♦ Pain associated with higher centre complaints
♦ Pain associated with neurological disturbance, such as clumsiness or weakness
♦ Pain associated with local tenderness, such as of the temporal artery
Table 18.3 Simplified diagnostic criteria for migraine adapted from the Headache Classification Committee of The International Headache Society (2004)
Repeated attacks of headache lasting 4–72 h that have these features, normal physical examination and no other reasonable cause for the headache:
At least 2 of
At least 1 of
♦ Unilateral pain
♦ Throbbing pain
♦ Photophobia and phonophobia
♦ Aggravation by movement
♦ Moderate or severe intensity
The management of secondary headache is generally self-evident: treatment of the underlying condition, such as an infection or mass lesion. An exception is the condition of chronic post-traumatic headache in which pain persists for long periods after head injury (Section 25.6.1). This is an interesting generic problem that may be seen after central nervous system infection, trauma, both blunt and surgical, intracranial bleeds, and other precipitants. While the syndrome is generally self-limiting up to 3–5 years after the event, treatment of the headache may be required if it is disabling (Section 18.3).
18.2.1 Clinical features
Migraine is generally an episodic headache with certain associated features, such as sensitivity to light, sound, or movement, and often with nausea or vomiting accompanying the headache (Table 18.3). None of the features is compulsory, and given that the migraine aura, visual disturbances with flashing lights or zig-zag lines moving across the fields, or other neurological symptoms, is reported in only about 20 per cent of patients, a high index of suspicion is required to diagnose migraine. In a blinded, controlled study of patients presenting to General Practitioners with a main complaint of headache it was migraine on more than 90 per cent of occasions; thus it seems clear that most headache patients seen in neurology clinics probably have migraine as the underlying problem.
A headache diary can often be helpful in making the diagnosis although usually the diary helps more in assessing disability or recording how often patients use acute attack treatments. Phenotyping headache remains a clinical art of mixing experience with an understanding of the problems likely to present. In differentiating the two main primary headache syndromes seen in clinical practice:
♦ migraine at its most simple level is headache with associated features, and tension-type headache is headache that is featureless, by features is meant throbbing pain; or sensitivity to sensory stimuli: visual, auditory, olfactory; or to head movement itself.
♦ most disabling headache is probably migrainous in biology.
18.2.2 Frequent migraine
If headache with associated features describes migraine attacks, then headachy describes the migraine sufferer over their lifetime. It is important to realize that the word migraine can both describe the attacks using standard criteria (Table 18.3), and describe the disorder itself, which is more than just the attacks themselves. The migraine sufferer inherits a tendency to have headache that is amplified at various times by their interaction with their environment, the much-discussed triggers. The brain of the migraineur seems more sensitive to sensory stimuli and to change; and this tendency is even more notably amplified in females during their menstrual cycle. The migraine sufferer does not habituate to sensory stimuli easily and so can be unfairly and often stimulated in the world in which they live and work. Migraine sufferers may have headache when they oversleep, when tired, when they skip meals, when stressed, or when relaxed. They are less tolerant to change and part of successful management is to advise them to maintain regularity in their lives in the knowledge of this fluctuating biology. It is this biology that marks migraine and which in clinical practice must override the phenotype of individual headaches.
It has been said that migraine can never occur daily, but few biological issues respect absolute rules. Chronic migraine very definitely occurs and in neurology or headache practice, is the very largest part of the group of headaches known collectively as chronic daily headache (Section 18.6). It is simply the most severe end of a complex biology and unsurprisingly often requires neurological input. Only development of disease markers will resolve diagnostic issues around daily headache. 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 does the patient have and more important, what cannot the patient do; what is their degree of disability? One can ask the patient directly to get a flavour for this, keep a diary or get a quick but accurate estimate using the Migraine Disability Assessment Scale, which is well-validated and very easy to use in practice (Fig. 18.4).
18.2.3 Principles of management
After diagnosis the management of migraine begins with an explanation of some aspects of the disorder to the patient. It is useful to explain that:
♦ migraine is an inherited tendency to headache; this is caused by the patient’s genes, therefore it cannot be cured but;
♦ migraine can be modified and controlled by lifestyle adjustment and the use of medicines; and
♦ migraine management takes time and co-operation when, for example a headache diary has to be collected, or inquiry made concerning the disability.
18.2.4 Non-pharmacological management
This approach aims to help the migrainous patient identify things that make the problem worse and encourage them to modify these. Patient associations can be very helpful with pamphlets for this form of education, and those of the Migraine Trust and Migraine Action Association in the United Kingdom, and the American Council for Headache Education ‘ACHE’ are recommended. Many patients will not find this approach rewarding and should not be pilloried for this. Patients need to know that the brain sensitivity in migraine varies, so that the effect of triggers will vary. This knowledge will remove considerable frustration on the patient’s part, will ring true to most as they have had the experience, and is biologically plausible, since it is exactly what one would predict from the channelopathic/ionopathic theory of migraine pathogenesis. The crucial lifestyle advice is to explain to the patient that migraine is a state of brain sensitivity to change. This implies that the migraine sufferer needs to regulate their lives: healthy diet, regular exercise, regular sleep patterns, avoiding excess caffeine, and alcohol and, as far as practical, modifying or minimizing changes in stress. The balanced life with less highs and lows will benefit most migraine sufferers.
18.2.5 Preventive treatments
The decision to start a patient on preventive treatment requires crucial input from the migraineur. The patient needs to have come to terms with the fact that they have an inherited, non-curable but manageable problem, and that they have sufficient disability to wish to take a medicine to reduce the affects of the disease on their life. Only then can the doctor explain the choices available and their relative merits. The basis of considering preventive treatment from a medical viewpoint is a combination of acute attack frequency and attack tractability. Attacks that are unresponsive to abortive medications are easily considered for prevention, while simply treated attacks may be less obviously candidates for prevention. The other part of the equation relates to what is happening with time. If a patient diary shows a clear trend of an increasing frequency of attacks it is better to introduce prevention early than to wait for the problem to become chronic.
A simple rule for frequency might be that for 1–2 headaches a month there is usually no need to start a preventive drug, for 3–4 it may be needed but not necessarily, and for 5 or more a month prevention should definitely be on the agenda for discussion. Options available for treatment are covered in detail in Table 18.4 and vary somewhat by country. The problem with preventives is not that there are none, but that they have fallen into usage for migraine from other indications. Often 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 that underlies migraine. Another key clinical point is that 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.
Table 18.4 Preventive drug treatments in migraine†
Selected side effects
0.5–2 mg daily
40–120 mg bd
Contraindicated in asthma
25–75 mg nocte
Note: some patients are very sensitive and may only need a total dose of 10 mg, although generally 1–1.5 mg/kg body weight is required
400–600 mg bd
Haematological or liver abnormalities
Care with a family history of glaucoma
900–3600 mg daily
1–6 mg daily
Retroperitoneal fibrosis (one month drug holiday is required every 6 months)
5–15 mg daily
20 mg daily
16 mg daily
400 mg daily
♦ Coenzyme Q10
100 mg tid
75 mg bd
6.25 mg tid
No Convincing Controlled Evidence
Controlled trials to demonstrate no effect
♦ SSRIs: fluoxetine
† Commonly used preventives are listed with reasonable doses and common side effects. The local national formulary should be consulted for detailed information.
‡ Compounds not widely considered as mainstream but with a positive randomized control trial against placebo.
‡‡ Non-pharmaceuticals with at least one positive randomized controlled trial against placebo.
Little has been done in terms of systematic study of patients with more intractable forms of migraine. Neuromodulation approaches are promising, largely by stimulation of the occipital nerve, and show that central processing of pain signals in migraine in the thalamus may be modified (Matharu et al. 2004a). This is an exciting and developing area.
18.2.6 Acute attack therapies
Acute attack treatments for migraine can be usefully divided into disease non-specific treatments, analgesics, and non-steroidal antiinflammatory drugs, and disease-specific treatments, ergot-related compounds, and triptans (Table 18.5). It must be said at the outset that most acute attack medications seem to have a propensity to aggravate headache frequency and can induce a state of refractory daily or near-daily headache, known as medication overuse headache. As evidence is gathered this seems to occur in patients with migraine: either a previous clear history or a family or personal history of headachiness. Codeine-containing compound analgesics are a particularly pernicious problem when available in over-the-counter preparations. One should advise patients with migraine who have two headache days a week or more to avoid their regular use. A proportion of patients who stop taking regular analgesics will have substantial improvement in their headache with a reduction in frequency, however, for some it will not make any difference. It is crucial to emphasize to the patient that standard preventive medications often simply do not work in the presence of regular analgesic use.
Table 18.5 Oral acute migraine treatments
(often used with anti-emetic/prokinetics, such as domperidone (10 mg) or metaclopramide (10 mg))
Aspirin (900 mg)
♦ Ergotamine (1–2 mg)
Paracetamol (1000 mg)
♦ Sumatriptan (50 or 100 mg)
♦ Naproxen (500–1000 mg)
♦ Naratriptan (2.5 mg)
♦ Ibuprofen (400–800 mg)
♦ Rizatriptan (10 mg)
♦ Tolfenamic acid (200 mg)
♦ Zolmitriptan (2.5 or 5 mg)
♦ Eletriptan (40 or 80 mg)
♦ Almotriptan (12.5 mg)
♦ Frovatriptan (2.5 mg)
NSAIDS: non-steroidal antiinflammatory drugs
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 or paracetamol 1000 mg with an anti-emetic. Aspirin is an effective strategy, has been proven so in double-blind controlled clinical trials, and is best used in its most soluble formulations. The alternative would be a strategy known as Stratified care, by 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 options. Patients use simpler options for their less severe attacks relying on more potent options when their attacks or circumstances demand them (Table 18.5).
Non-specific acute migraine attack treatments. Since simple drugs, such as aspirin and paracetamol, are cheap and can be very effective, they can be employed in many patients. Dosages should be adequate and the addition of domperidone 10 mg orally or metaclopramide 10 mg orally can be very helpful. Non-steroidal antiinflammatory drugs can 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 anti-emetic, ibuprofen 400–800 mg orally or tolfenamic acid 200 mg orally can be extremely effective.
Specific acute migraine attack treatments. When simple analgesic measures fail or more aggressive treatment is required, the specific anti-migrainous treatments are required (Table 18.6). While ergotamine remains a useful anti-migraine compound it can no longer be considered the treatment of choice in acute migraine (Tfelt-Hansen et al. 2000). There are particular situations in which ergotamine is very useful, but its use must be strictly controlled as ergotamine overuse produces dreadful headache in addition to various 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 by considering their pharmacological, physicochemical, and pharmacokinetic features (Goadsby 2000), as well as the formulations that are available (Goadsby et al. 2002).
Table 18.6 Clinical stratification of acute specific migraine treatments, given orally unless otherwise indicated
Failed analgesics/non-steroidal antiinflammatory drugs
Sumatriptan 50 mg or 100 mg
Almotriptan 12.5 mg
Rizatriptan 10 mg
Eletriptan 40 mg
Zolmitriptan 2.5 mg
Slower effect/better tolerability
Naratriptan 2.5 mg
Frovatriptan 2.5 mg
Ergotamine 1–2 mg
Dihydroergotamine nasal spray 2 mg
Early nausea or difficulties taking tablets
Zolmitriptan 5 mg nasal spray Sumatriptan 20 mg nasal spray
Rizatriptan 10 mg MLT wafer
Ergotamine 2 mg (most effective rectally /usually with caffeine)
Naratriptan 2.5 mg
Almotriptan 12.5 mg
Eletriptan 40 mg
Tolerating acute treatments poorly
Naratriptan 2.5 mg
Almotriptan 12.5 mg
Zolmitriptan 5 mg nasal spray
Sumatriptan 25 mg rectally
Sumatriptan 6 mg subcutaneously
Menstrually related headache
Dihydroergotamine nasal spray
Very rapidly developing symptoms
Zolmitriptan 5 mg nasal spray
Sumatriptan 6 mg subcutaneously
Dihydroergotamine 1 mg intramuscularly
18.3 Tension-type headache
18.3.1 Clinical features
As its name suggests, tension-type headache tension-type headache is a term that describes the headache form most in need of pathophysiological understanding. Consider for a moment how hard it is to study something that is commonly considered to be well-understood, and then ask what is the essence of tension-type headache? Tension-type headache is diagnosed commonly, and while the phenotype is common much of the disabling headache that goes under the name tension-type headache is likely to be chronic migraine in terms of its biology. Tension-type headache has two forms:
♦ episodic tension-type headache, where attacks occur on less than 15 days a month
♦ chronic tension-type headache where attacks, on average over time, are seen on 15 days or more a month.
This is part of the broader clinical syndrome of chronic daily headache, but these terms are not equal.
Tension-type headache has been defined by the International Headache Society both for its episodic and chronic forms, although the admixture of symptoms allowed has consistency problems. A useful clinical approach is to diagnose tension-type headache when the headache is completely featureless: no nausea, no vomiting, no photophobia, no phonophobia, no osmophobia, no throbbing, and no aggravation with movement. Such an approach neatly divides migraine, which has one of more of these features and is the main differential diagnosis, from tension-type headache.
The pathophysiology of tension-type headache is very poorly understood. This results from the fact that the name implies to most that it is a product of nervous tension, for which there is no clear evidence, and the definitions employed have undoubtedly admitted patients with migraine to the studies. Moreover, the concept that tension-type headache in some way involves muscle contraction is spurious since the evidence is that muscle contraction is no more likely that it is in migraine. It seems likely that tension- type headache will be due to a primary disorder of central nervous system pain modulation alone, to contrast it with migraine, which is a much more generalized disturbance of sensory modulation. There are data suggesting a genetic contribution to tension-type headache but one must question these since they have been gathered with probably faulty diagnostic criteria.
Adopting the clinical approach to tension-type headache outlined above results in diagnosing a headache form that is usually less disabling, and more in the category of irritating. Its episodic form is generally amenable to simple analgesics, paracetamol, acetaminophen, aspirin, or non-steroidal antiinflammatory drugs, which can be purchased over the counter. There are clear clinical studies to demonstrate that triptans in tension-type headache alone are not helpful, although germane to the above discussion, triptans are effective in tension-type headache where the patient also has migraine. Amitriptyline is the only treatment for chronic tension- type headache with a clear evidence base; the other tricylics, selective serotonin reuptake inhibitors or the benzodiazepines have not been shown in controlled trials to be effective. Similarly, there is no controlled evidence for the use of electromyographic biofeedback, relaxation therapy, or acupuncture. Botulinum toxin has been shown reasonably clearly to be ineffective. Stress management has been shown to be an effective approach in a controlled trial.
18.4 Trigeminal-autonomic cephalalgias
18.4.1 Cluster headache
Cluster headache is a rare form of primary headache with a population frequency of 0.1 per cent. It is covered in a specialized book (Olesen and Goadsby 1999). It is about as common as Multiple Sclerosis in the United Kingdom, and must be regarded as a disorder best managed by neurologists. It is perhaps the most painful condition in humans; in the cohort of more than 800 patients seen at the National Hospital not a single one has had a more painful experience, including childbirth, multiple fractures of the limbs, or renal stones. It is one of a group of conditions known now as Trigeminal-autonomic cephalalgias, and needs to be differentiated from other trigeminal-autonomic cephalalgias (Goadsby and Lipton 1997) and the short-lasting headaches without cranial autonomic symptoms, such as lacrimation or conjunctival injection (Table 18.7).
Table 18.7 Primary headache—cluster headache, other trigeminal autonomic cephalalgias, and short-lasting headaches*
Trigeminal autonomic cephalalgias
Other short-lasting headaches
*Beware of pituitary tumour-related headache in the differential diagnosis of these trigeminal autonomic cephalalgias.
† SUNCTs Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing..
The core feature of cluster headache is periodicity, be it circadian or in terms of active and inactive bouts over weeks and months (Table 18.8). The typical cluster headache patient is male, with a 3:1 predominance, who has bouts of 1–2 attacks of relatively short duration unilateral pain every day for bouts of 8–10 weeks a year. They are generally perfectly well between times. Patients with cluster headache tend to move about during attacks, pacing, rocking, or even rubbing their head for relief. The pain is usually retro-orbital boring and very severe. It is associated with ipsilateral symptoms of cranial parasympathetic autonomic activation: a red or watering eye, the nose running or blocking, or cranial sympathetic dysfunction: eyelid droop. Cluster headache is likely to be a disorder involving central pace-maker regions of the posterior hypothalamus (Fig. 18.2) (May et al. 1998; 1999a)
Table 18.8 Diagnostic criteria for cluster headache (Headache Classification Committee of The International Headache Society 2004)
3.1 Diagnostic criteria
3.1.1 Episodic cluster headache
Description: Occurs in periods lasting 7 days to 1 year separated by pain-free periods lasting 1 month or more
3.1.2 Chronic cluster headache
Description: Attacks occur for more than 1 year without remission or with remissions lasting less than 1 month.
The trigeminal-autonomic cephalalgias: cluster headache, paroxysmal hemicrania, and the syndrome of shortlasting unilateral neuralgiform headache attacks with conjunctival injection or tearing known as SUNCT, present a distinct group to be differentiated from short-lasting headaches that do not have prominent cranial autonomic syndromes, notably trigeminal neuralgia, idiopathic or primary stabbing headache, and hypnic headache (Goadsby 2002a). By determining the cycling pattern, length of attack, frequency of attack, and timing of the attacks, most patients can be usefully classified. The importance of clinical classification of this group is threefold. First, the clinical phenotype determines the likely secondary causes that must be considered and appropriate investigations ordered. Secondly, the appropriate classification gives clarity to the patient with a clear diagnosis and allows the physician to draw on available literature to comment on natural history. Thirdly, the correct diagnosis determines therapy that can be very different in these conditions, being very good if the diagnosis is correct but probably ineffective if it is not (Table 18.9).
Table 18.9 Differential diagnosis of short-lasting headaches
Primary stabbing headache
1–8 per day
1–40 per day
Cutaneous trigger to attacks
SUNCT, Short-lasting neuralgiform headache attacks with conjunctival injection and tearing.
*SUNCT generally has no refractory period to trigger additional attacks, while this is a very common feature of trigeminal neuralgia.
18.4.2 Managing cluster headache
Cluster headache is managed using acute attack treatments and preventive agents. Acute attack treatments are usually required by all cluster headache patients at some time, while preventives can seem almost life-saving for the patients with chronic cluster headache and are often needed to shorten the active periods in patients with the episodic form of the disorder.
Preventive treatments. The options for preventive treatment in cluster headache depend on the bout length (Table 18.10). Patients with short bouts require medicines that act quickly but will not necessarily be taken for long periods, whereas those with long bouts or indeed those with chronic cluster headache require safe, effective medicines that can be taken often for long periods. Most experts now favour verapamil as the first-line preventive treatment when the bout is prolonged, or in chronic cluster headache. By contrast, limited courses of oral corticosteroids or methysergide can be very useful strategies when the bout is relatively short.
Table 18.10 Preventive management of cluster headache
Episodic cluster headache
Episodic cluster headache and prolonged chronic cluster headache
♦ Greater occipital nerve injection
♦ (Daily nocturnal ergotamine)
? = unproven but promising.
Verapamil has been suggested as a useful option for the last decade and compares favourably with lithium. What has clearly emerged from clinical practice is the need to use higher doses than had initially been considered and certainly higher than those used in cardiological indications. Although most patients will start on doses as low as 40–80 mg twice daily, doses up to 960 mg daily and beyond are now employed (Olesen and Goadsby 1999). Side effects, such as gingival hyperplasia, constipation, and leg swelling, can be a problem, but more difficult is the issue of cardiovascular safety. Verapamil can cause heart block by slowing conduction in the atrioventricular node as demonstrated by prolongation of the A–H interval. Given that the PR interval on the electrocardiogram is made up of atrial conduction, A–H and His bundle conduction, it may be difficult to monitor subtle early effects as verapamil dose is increased. Given that the effects on the atrioventricular node take up to 10 days to manifest, 2-week intervals are recommended between dose changes on the first exposure, with electrocardiograms prior the next escalation, and 6-monthly electrocardiograms after the dose is established.
Acute attack treatment. Cluster headache attacks often peak rapidly and thus require a treatment with quick onset. Many patients with acute cluster headache respond very well to treatment with oxygen inhalation. This should be given as 100 per cent oxygen at 10–12 l/min for 15–20 min. It is important to have a high flow and high oxygen content. Injectable sumatriptan 6 mg has been a boon for many patients with cluster headache. It is effective, rapid in onset, and with no evidence of tachyphylaxis. Sumatriptan 20 mg and Zolmitriptan 5 mg nasal sprays are effective in acute cluster headache in controlled trials, and offer a useful option for patients who may not wish to self-inject daily. Sumatriptan is not effective when given pre-emptively as 100 mg orally three times daily, and there is no evidence that it is useful when used orally in the acute treatment of cluster headache; indeed it can be associated with medication overuse headache problems.
Surgical treatment. The surgical treatment of cluster headache has been completely revolutionized with the introduction of neuromodulation techniques. Surgical treatment of cluster headache is reserved for the most refractory patients, typically with chronic cluster headache. Destructive procedures such as pterygopalatinectomy or radiofrequency lesions of the trigeminal ganglion have been used, the former without clear effects, and the latter being helpful but often at significant cost, including ocular complications or anaesthesia dolorosa. Trigeminal rhizotomy has also been employed, with all the complications of radiofrequency lesions and the occasional death. Set against this is the functional imaging describing activations in the posterior hypothalamic region (May et al. 1998) directly leading to deep brain stimulation approaches in the same region that seem highly effective (Leone et al. 2004). A further approach is that of occipital nerve stimulation, which is very promising as a non-invasive approach to the management of intractable chronic cluster headache (Burns et al. 2007).
18.4.3 Paroxysmal hemicrania
Sjaastad and Dale (1976) first reported eight cases of a frequent unilateral severe but short-lasting headache without remission coining the term chronic paroxysmal hemicrania. The mean daily frequency of attacks varied from 7 to 22 with the pain persisting from 5 to 45 min on each occasion. The site and associated autonomic phenomena were similar to cluster headache, but the attacks were suppressed completely by indomethacin. A subsequent review of 84 cases showed a history of remission in 35 cases whereas 49 were chronic. By analogy with cluster headache the patients with remission have been referred to as episodic paroxysmal hemicrania (Kudrow et al. 1987) and those with the non-remitting form chronic paroxysmal hemicrania; the overall syndrome can be simply called paroxysmal hemicrania.
The essential features of paroxysmal hemicrania are (Table 18.11):
♦ unilateral, usually fronto-temporal, very severe pain;
♦ short-lasting attacks of 2–45 min;
♦ very frequent attacks, usually more than 5 a day;
♦ marked autonomic features ipsilateral to the pain; and
♦ robust, quick and excellent response to indomethacin in less than 72 h.
Table 18.11 Paroxysmal hemicrania (Headache Classification Committee of The International Headache Society 2004)
3.2 Diagnostic criteria:
3.2.1 Episodic paroxysmal headache
Description: Occurs in periods lasting 7 days to one year separated by pain free periods lasting one month or more
3.2.2 Chronic paroxysmal headache
Description: Attacks occur for more than one year without remission or with remissions lasting less than one month.
The pathophysiology of paroxysmal hemicrania is marked by activations on positron emission tomography in the contralateral posterior hypothalamus and contralateral ventral midbrain (Matharu et al. 2006). The posterior hypothalamic activity is shared with cluster headache, SUNCT, and hemicrania continua, while the ventral midbrain activity is only seen in hemicrania continua (Section 18.5.7), which remarkably is also an indomethacin-sensitive primary headache.
The therapy of paroxysmal hemicrania is complicated by gastrointestinal side effects seen with indomethacin, although thus far there is no reliable alternative option. Piroxicam has been suggested to be helpful, although not as effective as indomethacin. By analogy with cluster headache verapamil has been used in paroxysmal hemicrania, although the response is not spectacular; higher doses require exploration. Paroxysmal hemicrania can co-exist with trigeminal neuralgia, the paroxysmal hemicrania-tic syndrome, just as in cluster-tic syndrome, and each component requires separate treatment. Secondary paroxysmal hemicrania has been reported with lesions in the region of the sella turcica, an arteriovenous malformation, cavernous sinus meningioma, and a parotid epidermoid. Secondary paroxysmal hemicrania is more likely if the patient requires high doses’ >200 mg/day, of indomethacin. Raised CSF pressure should be suspected in apparent bilateral paroxysmal hemicrania. It is worth noting that indomethacin reduces CSF pressure by an unknown mechanism. It is appropriate to image patients, with MRI when practical, when a diagnosis of paroxysmal hemicrania is being considered.
18.4.4 Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing or cranial autonomic activation: SUNCT/SUNA
Sjaastad (1989) reported three male patients whose brief attacks of pain in and around one eye were associated with sudden conjunctival injection and other autonomic features of cluster headache. The attacks lasted only 15–60 s and recurred 5–30 times per hour, and could be precipitated by chewing or eating certain foods, such as citrus fruits. They were not abolished by indomethacin. Brain imaging has suggested that they share with cluster headache and paroxysmal hemicrania the feature on activation studies of involvement of the posterior hypothalamic region (May et al. 1999b). Of the patients recognized with this problem males dominate slightly and the paroxysms of pain may last between 5 and 300 s, although longer duller interictal pains are recognized, as are longer attacks with a saw-tooth pattern (Cohen and Goadsby 2006b). The conjunctival injection seen with SUNCT is often the most prominent autonomic feature and tearing may be very obvious. If one of either conjunctival injection or tearing are absent, or neither are present but another cranial autonomic symptom is seen, the term SUNA is used (Table 18.12). The two clinical features of SUNCT/SUNA are that the attacks are triggerable and when triggerable there is no refractory period to triggering further attacks. The latter serves as a very useful distinction between SUNCT/SUNA and trigeminal neuralgia. SUNCT/SUNA can be treated very often with lamotrigine, and if that is unhelpful topiramate or gabapentin. Carbamazepine often has a useful but incomplete effect.
Table 18.12 Proposed diagnostic criteria for short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA) (Headache Classification Committee of The International Headache Society 2004)
3.3R Diagnostic criteria:
A 3.3.1 Episodic SUNCT/SUNA
Description: SUNA attacks occurring for 7 days to 1 year with pain free intervals longer than 1 month
A 3.3.2 Chronic SUNCT/SUNA
Description: At least 2 attack periods last 7 days to 1 year separated by remission periods of less than one month (untreated).
Secondary SUNCT and associations. The literature reports a number of patients with secondary SUNCT syndromes that invariably have lesions involving the posterior fossa. Two reported patients had homolateral cerebellopontine angle arteriovenous malformations diagnosed on MRI, while another had a cavernous hemangioma of the brainstem seen only on MRI. Structural deformity involving the posterior fossa, including osteogenesis imperfecta and craneosynostosis, have presented as SUNCT-like syndromes, as have pituitary tumours. A posterior fossa lesion causing otherwise typical SUNCT has also been noted in HIV/AIDS. These cases highlight the need for cranial MRI in the diagnostic evaluation of SUNCT. Cases with both SUNCT and trigeminal neuralgia have been reported. Given that the attacks are short this can be a challenging clinical problem. The differential diagnosis turns around the degree of cranial autonomic activation, which may be seen to some degree in trigeminal neuralgia but is very prominent in SUNCT, and the lack of a refractory period to triggering of attacks in SUNCT.
18.5 Other primary headaches
18.5.1 Stabbing headache
Short-lived jabs of pain, defined as primary stabbing headache (Headache Classification Committee of The International Headache Society 2004) are well documented in association with most types of primary headache.
The essential clinical features are:
♦ pain confined to the head, although rarely is it facial;
♦ stabbing pain lasting from 1 to many seconds and occurring as a single stab or a series of stabs; and
♦ recurring at irregular intervals of hours to days.
Raskin and Schwartz (1980) described sharp, jabbing pains about the head resembling a stab from an ice-pick, nail, or needle. They compared the prevalence of such pains in 100 migrainous patients and 100 headache-free controls. Only three of the control subjects had experienced ice-pick pains compared with 42 of the migraine patients, of whom 60 per cent had more than one attack per month. The pains affected the temple or orbit more often than the parietal and occipital areas and often occurred before or during migraine headaches. The sites of these pains generally coincide with the site of the patients’ habitual headache. Retroauricular and occipital region pains are also well described and these respond promptly to indomethacin. Stabbing headaches have been described in conjunction with cluster headaches, and generally are experienced in the same area as the cluster pain. Sjaastad described ‘jabs and jolts’ lasting less than a minute in patients with chronic paroxysmal hemicrania (Antonaci and Sjaastad 1989). These longer attacks are probably part of the spectrum of stabbing headache. It is of interest that stabbing pains generally are not accompanied by cranial autonomic symptoms. The response of idiopathic stabbing headache to indomethacin, 25–50 mg twice to three times daily, is generally excellent. As a general rule the symptoms wax and wane and after a period of control on indomethacin it is appropriate to withdraw treatment and observe the outcome. Most patients will not want treatment when the nature of the problem is unexplained and they are reassured that the attacks are not sinister in any way.
18.5.2 Cough headache
Sharp pain in the head on coughing, sneezing, straining, laughing, or stooping has long been regarded as a symptom of organic intracranial disease, commonly associated with obstruction of the CSF pathways. The presence of an Arnold–Chiari malformation or any lesion causing obstruction of CSF pathways or displacing cerebral structures must be excluded before cough headache is assumed to be benign. Cerebral aneurysm, carotid stenosis, and vertebrobasilar disease may also present with cough or exertional headache as the initial symptom. The term ‘Benign Valsalva’s manoeuvre-related headache’ covers the headaches provoked by coughing, straining, or stooping but cough headache is more succinct and so widely used it is unlikely to be displaced.
The essential clinical features of benign and primary cough headache are:
♦ bilateral headache of sudden onset, lasting minutes, precipitated by coughing;
♦ may be prevented by avoiding coughing; and
♦ diagnosed only after structural lesions, such as posterior fossa tumour, have been excluded by neuroimaging.
Comparing benign cough with benign exertional headache Pascual and colleagues (1996) reported that the average age of their patients with benign cough headache was 43 years, and thus older than their patients with exertional headache. Indomethacin is the medical treatment of choice in cough headache. Raskin (1995) followed up an observation of Sir Charles Symonds reporting that some patients with cough headache are relieved by lumbar puncture. This is a simple option when compared to prolonged use of indomethacin. The mechanism of this response remains unclear.
18.5.3 Exertional headache
The relationship of this form of headache to cough headache is unclear and certainly much is shared. Indeed the relationship to migraine also requires delineation. Credit must be given to Hippocrates for first recognizing this syndrome when he wrote: ‘one should be able to recognise those who have headache from gymnastic exercises, or walking, or running, or any other unseasonable labour, or from immoderate venery’”.
The clinical features are:
♦ pain specifically brought on by physical exercise;
♦ bilateral and throbbing in nature at onset and may develop migrainous features in those patients susceptible to migraine;
♦ lasts from 5 min to 24 h; and
♦ prevented by avoiding excessive exertion, particularly in hot weather or at high altitude.
The acute onset of headache with straining and breath holding, as in weightlifter’s headache, may be explained by acute venous distension. The development of headache after sustained exertion, particularly on a hot day, is more difficult to understand. Anginal pain may be referred to the head, probably by central connections of vagal afferents and may present as exertional headache, so called cardiac cephalgia. The link to exercise is the important clinical clue. Pheochromocytoma may occasionally be responsible for exertional headache. Intracranial lesions or stenosis of the carotid arteries may have to be excluded as for benign cough headache. Headache may be precipitated by any form of exercise and often has the pulsatile quality of migraine. The most obvious form of treatment is to take exercise gradually and progressively whenever possible. Indomethacin at daily doses varying from 25 to 150 mg is generally very effective in benign exertional headache. Indomethacin 50 mg, ergotamine tartrate 1–2 mg orally, dihydroergotamine by nasal spray, or methysergide 1–2 mg orally given 30–45 min before exercise are useful prophylactic measures.
18.5.4 Sex headache
Sex headache may be precipitated by masturbation or coitus and usually starts as a dull bilateral ache while sexual excitement increases, suddenly becoming intense at orgasm. The term orgasmic cephalgia is not accurate since not all sex headaches require orgasm. Three types of sex headache have been discussed, a dull ache in the head and neck that intensifies as sexual excitement increases, a sudden severe ‘explosive’ headache occurring at orgasm, and a postural headache. This last is now recognized as being due to low CSF volume due to a CSF leak developing after coitus and is usefully considered with ‘new daily persistent headache’ as a ‘secondary chronic daily headache’ (Section 18.6.7).
The essential clinical features of sex headache are:
♦ precipitation by sexual excitement;
♦ bilateral at onset; and
♦ prevented or eased by ceasing sexual activity before orgasm.
Headaches developing at the time of orgasm are not always benign. Subarachnoid haemorrhage (Section 35.16) was precipitated by sexual intercourse in 5 per cent of 66 cases reported by Fisher (1968) and 12 per cent of 50 cases studied by Lundberg and Osterman (1974). One young man reported developed a brainstem thrombosis and another a left hemisphere infarction. Sex headache is reported by men more often than women and may occur at any time during the years of sexual activity. It may develop on several occasions in succession and then not trouble the patient again, despite no obvious change in sexual technique. In patients who stop sexual activity when headache is first noticed, it may subside within a period of 5 min to 2 h, and it is recognized that more frequent orgasms can aggravate established sex headache. About one-third of the patients with sex headache have a history of exertional headaches, but there is no excess of cough headache in patients with sex headache. In about 50 per cent of patients sex headache will settle in 6 months. Migraine is reported in about 25 per cent of patients with sex headache.
Primary sex headaches are usually irregular and infrequent in recurrence, so management can often be limited to reassurance and advice about ceasing sexual activity if a milder, warning headache develops. When the condition recurs regularly or frequently, it can be prevented by the administration of propranolol, but the dosage required varies from 40 to 200 mg daily. An alternative is the calcium channel-blocking agent diltiazem 60 mg three times daily. Ergotamine 1–2 mg or indomethacin 25–50 mg taken about 30–45 min prior to sexual activity can also be helpful.
18.5.5 Hypnic headache
This syndrome was first described in patients aged from 67 to 84 who had headache of a moderately severe nature that typically came on a few hours after going to sleep (Raskin 1988). These headaches last from 15 to 30 min, are typically generalized, although may be unilateral, and can be throbbing. Patients may report falling back to sleep only to be awoken by a further attack a few hours later with up to three repetitions of this pattern over the night. In a large series of 19 patients, 84 per cent were female and the mean age at onset was 61±9 years (Dodick et al. 1998). Headaches were bilateral in two-thirds and in 80 per cent of cases mild or moderate. Three patients reported similar headaches when falling asleep during the day. None had photophobia or phonophobia and nausea is unusual.
Patients with this form of headache generally respond to a bedtime dose of lithium carbonate 200–600 mg and in those that do not tolerate this, verapamil or methysergide at bedtime may be alternative strategies. Two patients who responded to flunarizine 5 mg at night have now been reported. One to two cups of coffee or caffeine 60 mg orally at bedtime was reported to be (Dodick et al. 1998) helpful. This is a simple approach that is effective in about one-third of patients. A patient poorly tolerant of lithium has been controlled using verapamil 160 mg at night.
18.5.6 Thunderclap headache
Sudden onset of severe headache may occur in the absence of sexual activity and the differential diagnosis includes the sentinel bleed of an intracranial aneurysm, cervicocephalic arterial dissection, and cerebral venous thrombosis. Headaches of explosive onset may also be caused by the ingestion of sympathomimetic drugs or tyramine-containing foods in a patient who is taking monoamine oxidase inhibitors, and can also be a symptom of pheochromocytoma. Whether thunderclap headache can be the presentation of an unruptured cerebral aneurysm is unclear. Day and Raskin (1986) reported a woman with three episodes of sudden onset of very severe headache who was found to have an unruptured aneurysm of the internal carotid artery, with adjacent areas of segmental vasospasm. In the absence of CT scan or CSF evidence of subarachnoid haemorrhage, studies indicate that such patients do very well, and there indeed seems to be a form of benign or primary thunderclap headache.
Wijdicks et al. (1988) followed up 71 patients whose CT scans and CSF findings were negative for an average of 3.3 years. Twelve patients had further such headache, and 31, 44 per cent, later had regular episodes of migraine or tension-type headache. Factors identified as precipitating the headache were sexual intercourse in three cases, coughing in four, and exertion in 12, while the remainder had no obvious cause. A history of hypertension was found in 11 and of previous headache in 22. Markus (1991) compared the presentation of 37 patients with subarachnoid haemorrhage and 189 with a similar thunderclap headache but normal CSF examination and could not discern any characteristic to distinguish the two conditions on clinical grounds.
Investigation of any sudden onset of severe headache, be it in the context of sexual excitement or isolated thunderclap headache, should be driven by the clinical context. The first presentation should be vigorously investigated with CT and CSF examination, and if possible MR imaging and angiography. Formal cerebral angiography should be performed if no primary diagnosis is forthcoming, and the clinical situation is particularly suggestive of intracranial aneurysm. Bearing in mind the entity of diffuse multi-focal reversible cerebral vasospasm, which may be seen in apparent primary thunderclap headache without there being an intracranial aneurysm, caution in interpretation of angiographic findings is crucial.
18.5.7 Hemicrania continua
Two patients were initially reported with this syndrome, a woman aged 63 years and a man of 53. They developed unilateral headache without obvious cause. One of these patients noticed redness, lacrimation, and sensitivity to light in the eye on the affected side. Both patients were relieved completely by indomethacin while other non-steroidal antiinflammatory drugs were of little or no benefit. 24 previously reported cases, with the addition of 10 new cases, including some with pronounced autonomic features resembling cluster headache, have been reviewed (Newman et al. 1992). Their case histories were divided into remitting and unremitting forms. Of the 34 patients reviewed, 22 were women and 12 men with the age of onset ranging from 11 to 58 years. The symptoms were controlled by indomethacin 75–150 mg daily. The essential features of hemicrania continua are:
♦ unilateral pain;
♦ pain is moderate and continuous but with fluctuations;
♦ complete resolution of pain with indomethacin; and
♦ exacerbations may be associated with autonomic features.
Apart from analgesic overuse as an aggravating factor, and a report in an HIV-infected patient, the status of secondary hemicrania continua is unclear. The ‘indotest’ has been proposed by which the intramuscular injection of indomethacin 50 mg could be used as a diagnostic tool (Antonaci et al. 1998). In hemicrania continua, pain was relieved in 73±66 min and the pain-free period was 13±8 h. A placebo-controlled modification of this test is preferred to the open-label version. Using the latter method in conjunction with positron emission tomography, it has been shown that there is activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua, as well as activation of the ipsilateral ventrolateral midbrain (Matharu et al. 2004b). The alternative is a trial of oral indomethacin, initially 25 mg three times daily, then 50 mg three times daily, and then 75 mg three times daily. One should allow up to 2 weeks for any dose to have a useful effect. Acute treatment with sumatriptan has been employed and reported to be of no benefit in hemicrania continua. Cyclo-oxygenase II antagonists seem effective in hemicrania continua, and topiramate is helpful in some patients, as is greater occipital nerve block.
18.6 Chronic daily headache
18.6.1 Range of conditions
Each of the above primary headache forms can occur very frequently. When a patient experiences headache on 15 days or more a month one can apply the broad diagnosis of chronic daily headache. Chronic daily headache is not one thing but a collection of very different problems with different management strategies. Crucially not all daily headache is simply tension-type headache (Table 18.13). This is the commonest clinical misconception in headache of confusing the clinical phenotype with the headache biotype. Population-based estimates of daily headache are remarkable, demonstrating that 4.5–4.8 per cent of the Western populations have daily or near daily headache. Daily headache may be primary or secondary, and it seems clinically useful to consider the possibilities in this way when making management decisions (Table 18.13). Population-based studies bear out clinical practice in that a large group of refractory daily headache patients overuse various over-the-counter preparations.
Table 18.13 Classification of chronic daily headache
> 4 h daily
< 4 h daily
Chronic cluster headache‡
♦ Head injury
Chronic tension-type headache†
Chronic paroxysmal hemicrania
Inflammatory, such as u Giant cell arteritis
♦ Behcets syndrome
Chronic central nervous system infection
New daily persistent headache†
Substance abuse headache
†May be complicated by analgesic overuse. In the case of substance abuse headache, the headache is completely resolved after the substance abuse is controlled (Headache Classification Committee of The International Headache Society 2004). Clinical experience suggests that many patients continue to have headache even after cessation of analgesic use. The residual headache probably represents the underlying headache biology.
‡Chronic cluster headache patients may have more than 4 h per day of headache. The inclusion of the syndrome here is to emphasize that, by and large, the attacks themselves are less than 4-h duration.
18.6.2 Chronic migraine
While it is widely accepted that some of the primary headaches, tension-type headache, cluster headache, and paroxysmal hemicrania, have chronic varieties, this question seems to have become unnecessarily troublesome for migraine. Few headache authorities would argue that migraine can never ever be chronic in terms of frequency, but the issue of whether patients with frequent headache, some of which fulfils standard criteria for migraine and some for tension-type headache, have a single migrainous biology is a very vexed one. Given that tension-type headache describes a phenomenology that is indistinct at best it seems unlikely that all its phenotype will have a single biological generator.
The concept behind chronic migraine is that some patients who inherit a migrainous biology end up with chronic daily headache. The typical patient will have daily headache of a dull, non-specific type, punctuated by more severe attacks that would often, in isolation, fulfil standard criteria for migraine. In headache speciality clinics this group is dominant, with about 90 per cent of patients having chronic migraine usually with analgesic overuse. It could be suggested that they have a biologically more difficult problem and this is the basis for their over-representation in referral centres.
If one applies the concepts outlined for tension-type headache (Section 18.3) then the diagnosis of chronic tension-type headache chronic tension-type headache is made when the patient has 15 days or more a month of entirely featureless generalized dull or pressure-like pain. When any of the attacks on some days have migrainous features: nausea, photophobia, phonophobia, throbbing, or aggravation with movement, then chronic migraine is diagnosed. The problem is not that both chronic migraine and chronic tension-type headache do not exist, but that some patients must simply have chronic tension-type headache and episodic migraine, two conditions; it is, however, simply impossible on clinical or other grounds to determine who they are. The approach outlined over-diagnoses chronic migraine, taking that to be a biological entity, and under-diagnoses the co-existence of chronic tension-type headache and episodic migraine. The converse would be true, if one diagnoses all as chronic tension-type headache and episodic migraine, then chronic migraine is missed. In clinical practice the concept of chronic migraine is particularly helpful. Given that the life-style advice is identical for both tension-type headache and migraine, and that the range of therapeutic options for preventive treatment in migraine is so much greater, the clinician loses nothing by diagnosing chronic migraine, and the patient has much to gain.
The management of chronic daily headache can be very rewarding. Most patients overusing analgesics respond very sensibly when the problem is explained.
The keys to managing daily headache are:
♦ exclude treatable causes (Table 18.13);
♦ obtain a clear analgesic history; and
♦ make a diagnosis of the primary headache type involved.
18.6.4 Medication overuse
For outpatients it is essential that analgesic use be reduced and eliminated. Patients can reduce their use either by, as an example, 10 per cent every week or two, depending on their circumstances, or if they wish, and there is no contraindication, by immediate cessation of use. Either approach can be facilitated by first keeping a careful diary over a month or two to be sure of the size of the problem. A small dose of an non-steroidal antiinflammatory drug, such as naproxen 500 mg bd if tolerated, will take the edge off the pain as the analgesic use is reduced. It is useful to note that non-steroidal antiinflammatory drug overuse does not seem to be a common cause of daily headache with once or twice daily dosage, whereas with more frequent dosing problems may develop. When the patient has reduced their analgesic use substantially a preventive should be introduced. It must be emphasized that preventive therapies often do not work in the presence of analgesic overuse. Thus the patient must reduce the analgesics or the entire attempt to use the preventive is largely wasted, although this helpful rule must have some limitations worthy of study. The most common cause of intractability to treatment is the use of a preventive when analgesics continue to be used regularly. For some patients this poses a difficult problem in management and often one must be blunt that some degree of pain is inevitable in the first instance if the problem is to be controlled ultimately.
Some patients with medication overuse will require admission for detoxification. Broadly they consist of two groups, those who fail outpatient withdrawal, or those who have a significant complicating medical indication, such as brittle diabetes mellitus, or complicating medicines, such as opioids, where withdrawal may be problematic as an outpatient. When such patients are admitted acute medications are withdrawn completely on the first day, unless there is some contraindication. Anti-emetics, such as domperidone oral or suppositories, and fluids are administered as required, as well as clonidine for opioid withdrawal symptoms. For acute intolerable pain during the waking hours intravenous aspirin 1g is useful and at night chlorpromazine by injection, ensuring adequate hydration. If the patient does not settle over 3–5 days a course of intravenous dihydroergotamine can be employed as Raskin described (Raskin 1986). As time goes by one feels that dihydroergotamine is indispensable in this setting; administered 8-hourly for 3 days, it can induce a significant remission that allows a preventive treatment to be established. Often 5-HT3 antagonists, such as ondansetron or granisetron, will be required with dihydroergotamine as it is essential to ensure that the patient does not have significant nausea.
18.6.5 Preventive treatments
The tricylics, amitriptyline or dothiepin, at doses up to 1 mg/kg are very useful in patients with chronic daily headache. Tricyclics are started in low dosage of 10–25mg daily and best given 12 h prior to when the patient wishes to wake up so as to avoid excessive morning sleepiness. The other (excessive) useful medications for these patients are the anticonvulsants, such as valproate, topiramate, and gabapentin. Valproate doses up to 1500 mg daily are used, starting at 200 mg bd and increasing to 400 mg or 600 mg bd as tolerated over 2–4-week intervals. The blood count and liver enzymes should be checked at baseline and the various side effects explained to patients, especially the foetal abnormalities to females. For topiramate one can start at 25 mg nightly and increase by 25 mg every 10–14 days to aim for 50 mg twice daily (Table 18.4). For gabapentin the dose is 1800–3600 mg daily; it is very well tolerated, although probably less effective from a population viewpoint. For some patients flunarizine can be very effective, as can methysergide or phenelzine.
18.6.6 New daily persistent headache
New daily persistent headache is a clinically distinct syndrome with a range of important possible causes (Table 18.14). From a nosological point of view all entities mentioned here could be placed at various categories by the Headache Classification Committee of The International Headache Society (2004). However, the term serves both patients and clinicians by highlighting a group of conditions some of which are curable. New daily persistent headache can have both primary and secondary forms (Table 18.14) and neurologists will be called on to diagnose and treat these patients.
Table 18.14 Differential diagnosis of new daily persistent headache
♦ Sub-arachnoid hemorrhage
♦ Featureless (tension-type)
♦ Low CSF volume headache
♦ Raised CSF pressure headache
♦ Post-traumatic headache*
♦ Chronic meningitis
*Includes post-infective forms.
The patient with new daily persistent headache presents with a history of headache on most if not all days that lasts from one day to the next. The onset of headache is abrupt, often from one moment to the next, although the current definition accepts a period of onset over three days. The typical history is for the patient to recall the exact day and circumstances, so from one moment to the next a headache develops that never leaves them. This presentation provokes certain key questions about the onset and behaviour of the pain. These need to be woven with the more generic questions that one asks a patient with persistent headache, to form a provisional diagnosis. The pressing issues arise from considering the differential diagnosis, particularly of the secondary headache forms. Although subarachnoid haemorrhage is listed for some logical consistency, as the headache may certainly come on from one moment to the next, it is not likely to produce diagnostic confusion in this group of patients. The issues surrounding late imaging and management of unruptured aneurysms are covered elsewhere (Section 35.16.6). Suffice to say that subarachnoid haemorrhage is so important that it must always be considered if only to be excluded, either by history or appropriate investigation.
Primary new daily persistent headache. Initial descriptions of primary new daily persistent headache recognized it to occur in both males and females. Migrainous features were common, with unilateral headache in about one-third and throbbing pain in about one-third. Nausea was reported in about half the patients, as was photophobia and phonophobia observed again in about half. A number of these patients have a previous history of migraine but not more than one might expect given the population prevalence of migraine. It is remarkable that the initial report noted that 86 per cent of patients were headache free at 24 months. It is general experience amongst headache specialist that primary new daily persistent headache is perhaps the most intractable and least therapeutically rewarding form of headache. In general one can classify the dominant phenotype, migraine or tension-type headache, and treat with preventives according to that sub-classification, as for patients with chronic daily headache. Primary new daily persistent headache with a tension-type headache phenotype is very unresponsive to treatment.
Secondary new daily persistent headache. The secondary causes of the syndrome of new daily persistent headache are worthy of consideration, as they have distinctive clinical pictures that can guide investigation (Table 18.14).
18.6.7 Low CSF volume headache
The syndrome of persistent low CSF volume headache is an important diagnosis not to miss. The more immediately obvious form of this problem is encountered commonly in neurology after lumbar puncture. In that situation the headache usually settles rapidly with bedrest. In the chronic situation the patient typically presents with a history of headache from one day to the next. The pain is generally not present on waking, worsens during the day, and is relieved by lying down. Recumbency usually improves the headache in minutes, and it takes only minutes to an hour for the pain to return when the patient is upright again. The patient may give a history of an index event: lumbar puncture or epidural injection, or a vigorous Valsalva, such as with lifting, straining, coughing, clearing the eustachian tubes in an aeroplane, or multiple orgasms. Patients may volunteer, or a history may be obtained, that soft drinks with caffeine provide temporary respite. Spontaneous leaks are recognized, and the clinician should not be put off the diagnosis if the headache history is typical but there is no obvious index event. As time passes from the index event the postural nature may be less obvious; certainly cases whose index event was several years prior to the eventual diagnosis are recognized. The term low volume rather than low pressure is used, since there is no clear evidence at which point the pressure can be called low. While low pressures, such as 0–5 cm CSF are usually identified, a pressure of 16 cm CSF has been recorded with a documented leak. One should be aware of the possibility of the development of subdural collections in patients with low CSF volume headaches, which makes imaging before any invasive studies all the more important.
The investigation of choice is MRI with gadolinium (Fig. 18.5), which produces a striking pattern of diffuse pachymeningeal enhancement, although in about 10 per cent of cases a leak can be documented without enhancement. This finding of diffuse meningeal enhancement is so typical that in clinical context immediate treatment is indicated. It is also common to see Chiari malformations on MRI with some degree of descent of the cerebellar tonsils. This is important from the neurologist’s viewpoint since surgery in such settings simply makes the headache problem worse. Any patient being considered for such surgery for a headache indication should be reviewed by a neurologist first. Alternatively the CSF pressure may be determined, or a leak sought with 111In-DPTA CSF studies that can demonstrate the leak and any early emptying of tracer into the bladder, indicative of a leak.
Treatment is bedrest in the first instance. False positive transient improvement in persistent low CSF volume headache with chiropractic and other similar therapies is recognized where the treatment necessitated the patient lying down for a prolonged period. Intravenous caffeine, 500 mg in 500 ml saline administered over 2 h, is the standard and often very efficacious treatment. The electrocardiogram should be checked for any arrthymia prior to administration. A reasonable practice is to carry out at least two infusions separated by 4 weeks after obtaining the suggestive clinical history and MRI with enhancement. Since intravenous caffeine is safe, and can be curative, by an unknown mechanism, it spares many patients the need for further tests. If that is unsuccessful, an abdominal binder may be helpful. If a leak can be identified, either by the radioisotope study, or by CT myelogram, or spinal T2-weighted MRI, an autologous blood patch is usually curative. In more intractable situations theophylline is a useful alternative that allows out-patient management.
18.6.8 Raised CSF pressure headache
As is the case for low CSF pressure states, raised CSF pressure as a cause of headache is well recognized by neurologists. Brain imaging can often reveal the cause, such as raised pressure due to a space-occupying lesion. The particular setting in which patients enter the spectrum of new daily persistent headache are those with idiopathic intracranial hypertension (Section 26.5.6) who present with headache without visual problems, particularly with normal fundi. It is recognized that intractable chronic migraine can be triggered by persistently raised intracranial pressure. These patients typically give a history of generalized headache that is present on waking, and gets better as the day goes on. It is generally worse with recumbency. Visual obscurations are frequently reported. Fundal changes on raised intracranial pressure would make the diagnosis relatively straightforward but it is in those without such changes that the history must drive investigation. Patients often report a curious whooshing sensation in the occipital region.
Brain imaging is mandatory if raised pressure is suspected, and it is most simple in the long run to obtain an MRI, and include MR venography. The CSF pressure should be measured by lumbar puncture taking care to do so when the patient is symptomatic, so that both the pressure and response to removal of 20 ml of CSF can be determined. A raised pressure and improvement in headache with removal of CSF is diagnostic of the problem. The visual fields should be formally documented even in the absence of overt ophthalmic involvement. Initial treatment can be with acetazolamide 250–500 mg twice daily. The patient may respond in weeks with improvement in headache. If this is not effective topiramate has many actions that may be useful in this setting: carbonic anhydrase inhibition, weight loss, and neuronal membrane stabilization probably through actions on phosphorylation pathways. A small number of severely disabled patients who do not respond to medical treatment will come to intracranial pressure monitoring and even shunting. This is exceptional and not to be undertaken without careful work-up.
18.6.9 Post-traumatic headache
The issue of post-traumatic headache is vexed. The existence of such a syndrome is accepted (Headache Classification Committee of The International Headache Society 2004). Much of the scientific discussion becomes marred by the often-quoted medico-legal morass concerning delayed effects of head injury (Section 25.6.1). The term is used here to indicate trauma in a very broad way. New daily persistent headache may be seen after a blow to the head but more commonly after an infective episode, typically viral, or in one case malarial meningitis. A recent series identified one-third of all patients with new daily persistent headache reported the headache starting after a flu-like illness. The patient may note a period in which they had a significant infection: fever, neck stiffness, photophobia, and marked malaise. The headache starts during that period and never stops. Investigation reveals no on going cause for the headache. It has been suggested that some patients with this syndrome have a persistent Epstein–Barr infection, but such a syndrome is anything but clearly delineated. A complicating factor will often be that the patient had a lumbar puncture during that illness, so a persistent low CSF volume headache needs to be considered initially. Post-traumatic headache may be seen after carotid artery dissection, sub-arachnoid hemorrhage, and following intracranial surgery for a benign mass. The underlying theme seems to be that a traumatic event involving the dura mater can trigger a headache process that lasts for many years after that event.
The treatment of this form of NDPH is substantially empirical. Tricyclics, notably amitriptyline, and anticonvulsants, valproate, topiramate, and gabapentin, have been used with good effects. The MAOI phenelzine may also be useful in carefully selected patients. On the positive side the headache seems to run a limited course of 3–5 years, so will eventually settle. It can certainly be very disabling in that period.
18.7 Other forms of secondary headache
These are summarized in Table 18.15.
Table 18.15 Other secondary headaches
♦ Cervicogenic headache (Section 18.7.2)
♦ Reader’s paratrigeminal neuralgia (Section 18.7.3)
♦ Headache as a presentation of cervical dystonia
♦ Headache in temporomandibular dysfunction (Section 19.3.1)
♦ Cardiac cephalalgia (Lance and Lambros 1998)
♦ Headache with endocrine disturbance, particularly pituitary tumour (Levy et al. 2005)
♦ Neck–tongue syndrome (Bogduk 1981)
♦ Red-ear syndrome (Lance 1996)
18.7.1 Giant cell arteritis
This is an important cause of headache because delay in steroid treatment may result in blindness due to retinal artery ischaemia (Section 12.4.4). It is also known as temporal arteritis or cranial arteritis. Patients are usually elderly with focal tenderness of the scalp which may be provoked markedly by resting the head on the pillow. Jaw claudication provoked by chewing is a characteristic but relatively uncommon feature. Constitutional symptoms are common, particularly weight loss, malaise, or polymyalgia rheumatica. An elevated ESR is a strong pointer to the diagnosis. The temporal artery may be tenderly inflamed, swollen, or pulseless (Fig. 18.6). On suspicion of this diagnosis steroid treatment should be started pending the result of temporal artery biopsy. The clinical features and pathogenesis of this vasculitic condition are considered in Section 36.2.8.
18.7.2 Cervicogenic headache
It is a time-honoured concept that the neck is responsible for much of what is seen in headache referral practice. Unfortunately as with much of history the good story is often ruined by the facts. Whilst there is little doubt that there is a rich overlap between the innervation of intracranial pain-producing structures by the ophthalmic division of the trigeminal nerve, and the posterior fossa and high cervical innervation by branches especially of the C2 dorsal root (Bartsch and Goadsby 2005), causality is complex. The Headache Classification Committee recognizes that head pain can arise from the neck and labels this cervicogenic headache (Headache Classification Committee of The International Headache Society 2004). The term has been used by others to define a syndrome (Antonaci et al. 2001) that is so confusing as to be useless in practice (Goadsby 2004). Most patients with neck discomfort and headache referred to specialty practice will have migraine. They will have neck stiffness or discomfort as a premonitory symptom that can clearly persist in all stages of the attack (Giffin et al. 2003). They may respond to local therapies, such as greater occipital nerve injection (Afridi et al. 2006), however, this implies no more than triggering, and is to be expected. The pursuit of neck pathology, and the treatment of patients who have migraine by manipulative or physical means has no support in the controlled literature, and is rarely of long-lasting value.
18.7.3 Raeder’s Syndrome
J.G. Raeder (1924) wrote a classical clinical-anatomical colocalization paper describing five patients with two key features: involvement of the trigeminal nerve and the oculo-sympathetic nerves. He sought to differentiate the restricted oculo-sympathetic findings from the classical Horner’s syndrome: cervical sympathetic dysfunction characterized by ptosis, miosis, anhidrosis, and enophthalmos. Since that time various terms have been employed, meanings defined, and classifications developed (Mokri 1982; Vijayan and Watson 1986). Raeder made an interesting clinical observation that pointed out the likely localization of a lesion adjacent the trigeminal nerve in the middle cranial fossa (Fig. 18.7). Solomon and Lustig (2000) recently set out the clinical cases that in many respects have illustrated the trigemino-sympathetic anatomy of the carotid artery, concluding that the use of the term Raeder’s paratrigeminal neuralgia had become corrupted to the point of being useless by careless attribution of cases that did not respect the anatomy. Conditions such as carotid disease, particularly dissection may give rise to pain and Horner’s syndrome, and cluster headache may lead to oculo-sympathetic loss and impaired sympathetic facial sweating (Drummond 1988a, b). In both situations forehead sweating may be impaired.
The key anatomical feature to be understood for Raeder’s syndrome is the relationship between the trigeminal nerve and the oculo-pupillary sympathetic fibres (Fig. 18.7). The trigeminal nerve lies in middle cranial fossa and in close proximity, paratrigeminally, there are a number of other cranial nerves. Most particularly for a short course the fibres that will innervate the levator palpebrae superioris, specifically Müller’s muscle, and the pupilo-dilator fibres without the sudomotor fibres for the forehead. A restricted lesion in middle cranial fossa might cause the syndrome of trigeminal nerve involvement, neuralgic pain or sensory change, with ptosis or miosis, or both, but no anhidrosis. Such a paratrigeminal oculo-sympathetic syndrome usefully reminds clinicians to pursue vigorously possible lesions of the middle cranial fossa with careful, and possibly repeated, imaging studies. Whether Raeder’s name should remain attached is open to debate (Goadsby 2002b).
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