DÄ internationalArchive17/2018Hints on Diagnosing and Treating Headache

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Hints on Diagnosing and Treating Headache

Dtsch Arztebl Int 2018; 115(17): 299-308; DOI: 10.3238/arztebl.2018.0299

May, A

Background: Headache, like dizziness, is one of the more common presenting complaints in outpatient care and in the emergency room. More than 200 varieties of headache have been described, and the false impression may arise that the diagnosis and treatment of these syndromes is a highly challenging task.

Method: This review is based on pertinent articles retrieved by a selective search in PubMed.

Results: In primary headache, the headache is not a symptom but a disease in its own right. There are four types of primary headache: migraine, tension headache, trigeminal autonomic cephalalgia, and other primary headache disorders. By definition, the physical examination is normal, including the neurological examination. Secondary headache, in contrast, is a symptom of another disease (e.g., a tumor or cerebral hemorrhage). Triptans and nonsteroidal anti-inflammatory drugs (NSAID) are the drugs usually given for the acute treatment and prophylaxis of migraine. In tension headache, NSAID are given acutely, and tricyclic drugs for prophylaxis. There are various options for the treatment of trigeminal autonomic cephalalgia syndromes such as cluster headache and paroxysmal hemicrania. For group 4 headaches (other primary headache disorders), the treatment must be chosen on an individual basis; indomethacin is often effective.

Conclusion: If the patient is clearly suffering from none of the four types of primary headache, the problem must be a headache of a secondary nature, potentially reflecting a dangerous underlying disease. The treatment of headache is usually successful and thus highly rewarding for physicians of all medical specialties.

The updated headache classification of the International Headache Society (IHS), released in January 2018, lists more than 200 different varieties of headache that can be differentiated from each other on the basis of the history and physical examination alone (1). This enormous profusion may seem intimidating to physicians, particularly as there is no laboratory or imaging test that can establish the diagnosis of primary headache or tell one type of primary headache apart from another.

Learning objectives

This review is intended to enable readers from all medical specialties:

  • to know the four classes of primary headache,
  • to know their differential diagnoses, and
  • to gain an overview of potential preventive strategies and medical treatment options.

Headache classifications and types of headache

It should be pointed out at the outset that the IHS classification of headache was created, not for clinicians, but for scientists. The idea was that scientific studies and drug trials can only be of informative value if the patients treated in them are drawn from a homogeneous population. Patients with headache syndromes that are similar or even related to the target syndrome of the study, but not identical to it, would water down the results. In line with this reasoning, the different types of headache were very rigidly defined; to lessen uncertainty, headache groups were defined that sometimes include only a very small number of patients but are always well-characterized and thus clearly distinguishable from from one another. As a result, 13 types of migraine alone are listed, and more than 200 types of headache overall. It was realized that practicing physicians would inevitably encounter patients whose headaches did not fit exactly into any of the defined types. Criticisms of the IHS classification to the effect that it is either incomplete or (on the other hand) too rigorous and detailed are often heard, but they are generally due to a misunderstanding of its purpose. Surprisingly, however, the classification has proven very useful in clinical practice. The differentiation of the types of primary headache from one another and, above all, from secondary headache on the basis of a thorough history and neurological examination alone generally functions so well that the likelihood of the patient’s having a dangerous condition can be estimated with high accuracy, and therefore imaging studies can be ordered if, and only if, they are indicated (2). The classification is surprisingly easy to use as well: headaches are classified as either primary or secondary. Primary headaches are those that are not caused by another disease, i.e., the headache itself is the disease. In patients with primary headaches, the general physical and neurological examinations are normal, by definition. The IHS classifies primary headaches into four types: migraine, tension headache, trigeminal autonomic cephalalgias (of which cluster headache is the most prominent variety), and group 4, other primary headache disorders (3). Group 4 consists of ten rare headache syndromes (Table 1) whose primary nature is well-established. The most common and therefore clinically most important headache syndromes in this class are the group of benign exertional headaches and the group of primary stabbing headaches (“jabs and jolts syndrome”). Secondary headaches, in contrast, are a symptom of another disease, e.g., a hemorrhage. Any headache that does not fit into any of the four primary headache types is a secondary and therefore potentially dangerous headache. There are a few prominent warning symptoms of secondary headaches that should prompt rapid referral to a neurologist and/or further laboratory tests or imaging studies:

  • the initial manifestation of headache of an atypical kind
  • an atypical clinical course
  • increasing severity of pain, or changing character of pain, in a patient with a known headache syndrome
  • the simultaneous appearance of other neurological symptoms or deficits
The main clinical features of primary headache syndromes
The main clinical features of primary headache syndromes
Table 1
The main clinical features of primary headache syndromes

In patients whose history is typical of one of the primary headache syndromes and whose neurological examination is normal, laboratory tests and imaging studies are more likely to yield incidental, clinically irrelevant findings than to reveal any problem that needs to be treated.

Most headaches can be effectively treated, and the treatment of headache is thus a rewarding activity for physicians of all specialties. In this review, the four primary types of headache are described, together with their differential diagnoses, clinical pitfalls, guideline-based treatment, and tips for difficult cases.

Migraine with and without aura

Migraine is a type of headache characterized by attacks that last 4–72 hours each. The pain is of a stabbing, often pulsatile character and is associated with vegetative symptoms such as nausea, as well as with oversensitivity to light and noise. Patients with a typical history and a negative neurological examination have an only 0.2% chance of harboring an intracranial finding that might conceivably be related to the pain—the same percentage as that of incidental intracranial findings when imaging studies are performed on the normal population (Table 2) (2). The location of the headache does not play a major role (nor does it for any other type of headache, except for the trigeminal autonomic syndromes). As in most types of headache, the pain of migraine often begins in the nuchal area and then spreads to the temporal or frontal area. This localizing pattern should not mislead the physician to attribute the headaches to the wrong cause: the symptoms of migraine may well include tension of the nuchal and cranial musculature and of the muscles of mastication, while independent lesions of the cervical spine only cause headache when they involve the three highest cervical vertebrae (4). The prodromal symptoms of migraine can also include cognitive disturbances, fatigue, visual disturbances such as blurry vision (not to be confused with a visual aura), fluid retention, and mood swings. Rare variants exist, such as basilar migraine (migraine with a brainstem aura) and retinal migraine (migraine accompanied by symptoms suggesting hypoperfusion of the retina or optic nerve, e.g., transient blindness). The two main clinical entities, however, are migraine with aura and migraine without aura.

Epidemiological data on primary headache types*
Epidemiological data on primary headache types*
Table 2
Epidemiological data on primary headache types*

An aura is defined as any neurological symptom that arises before the headache of migraine and that meets the following criteria (5):

  • More than 90% of auras are visual, consisting either of positive phenomena (flicker, “fortification figures”) or of negative phenomena (such as hemianopsia). In as many as 30% of cases, there are neurological symptoms of other kinds in addition, most commonly tingling on the face, arm or leg on one side of the body, or aphasia.
  • The aura generally arises before the headache.
  • The aura generally lasts no longer than 60 minutes.

Auras with different features—longer duration, nonvisual, arising after the pain—are so rare that patients presenting to the emergency room with such symptoms should always be suspected of having something other than migraine. The most sensitive feature that differentiates an aura from ischemia is spreading: aura symptoms expand gradually to cover an ever larger area, while ischemic symptoms present in their full extent, suddenly, at the outset (whence, of course, the term “stroke”). Fortification figures, for example, begin as a paracentral visual disturbance and then spread outward to the periphery of the visual field. Once the outer edge has been reached, the visual disturbance ends, and the headache begins.

Auras without headache most commonly arise in persons who previously had typical migraine (either with or without aura). These persons are often of advanced age, in which case a disturbance of cerebral perfusion must be ruled out before any treatment is begun (2). The auras themselves cannot be treated, although, if they are very frequent, their frequency, duration, and/or severity can usually be lessened appreciably with migraine-prophylactic drugs. There is good evidence that topiramate and lamotrigine are effective for this purpose. In the author’s personal clinical experience, flunarizine (5 mg nocte) is the most effective drug, followed by lamotrigine (25–100 mg nocte).

The term “chronic migraine” (6) refers, by definition, to headaches that have been present on at least 15 days per month for at least 3 consecutive months, and that have met the defining criteria for migraine on at least 8 days in each month. The main clinically controllable risk factors are the ineffective and too frequent acute treatment of headaches (>10 days per month), and excessive body weight (6). Chronic migraine that has no analgesic-induced component is treated prophylactically in the the same way as episodic migraine. Botulinum toxin can be used to treat chronic migraine, but it is ineffective against episodic migraine (7).

The treatment of migraine

The treatment of migraine has two components: acute treatment and prophylaxis. Analgesics (usually nonsteroidal anti-inflammatory drugs [NSAIDs]) or specific anti-headache drugs (triptanes) are used for acute treatment. The correct dosing of NSAIDs is essential (acetylsalicylic acid [ASA], 500–1000 mg; ibuprofen, 400–800 mg). Triptans are the most effective drugs for combatting acute migraine attacks. Ergotamine is hardly ever given any more because of its side effects. Patients with marked nausea may additionally need an antiemetic drug, e.g., metoclopramide or domperidone (8). All analgesics, including triptans, can increase the frequency of attacks and cause drug-induced continuous headache if they are taken too frequently (9). It follows that analgesics, including triptans, should be taken on no more than 8–10 days per month. Moreover, triptans have a vasoconstrictive effect. Migraine auras are themselves associated with (mild) cerebral hypoperfusion; thus, patients with auras should take triptans only once the aura has come to an end and the headache has begun.

Patients who present with migraine as an emergency (in the emergency room or to the emergency medical services) usually need parenteral medication. The drugs available for this purpose include sumatriptan (given subcutaneously) and acetylsalicylic acid (given intravenously). Intravenous acetaminophen is no more effective than placebo. In the rare situation of status migrainosus (a migraine attack lasting longer than 72 hours), cortisone administration can terminate the symptoms; the dose is either 250 mg IV or 60–100 mg po, on two consecutive days if necessary (10).

Patients who regularly suffer from unusually long migraine attacks, or from more than three attacks per month, stand to benefit from prophylactic treatment (see the new edition of the AWMF guideline, Spring 2018 [in German]: http://www.awmf.org/leitlinien/detail/ll/030–057.html). The goal of prophylactic treatment is to lessen the frequency, severity, and duration of migraine attacks and to prevent drug-induced continuous headache. Drugs for prophylaxis include metoprolol (50–100 mg/d) and propanolol, flunarizine (5–10 mg/d), amitriptyline (25–75 mg/d), valproic acid (500–600 mg/d), and topiramate (50–100 mg/d). Pregnancy must be excluded before valproic acid is given. The initial dose-escalation phase of any of these drugs should be at least 4 weeks long, and their efficacy can only be assessed after 8–10 weeks of treatment. A prophylactic drug that has been found to be effective is generally given for a further 6–12 months, after which the patient is weaned off it if possible. A headache diary (available at www.dmkg.de and elsewhere) should be used to establish the indication for prophylactic treatment and then to monitor its efficacy.

The first biological migraine-prophylactic drugs are expected to become available this year or next: clinical trials have demonstrated that anti-CGRP antibodies are effective and have only rare adverse effects (1113). CGRP (calcitonin gene–related peptide) is a vasoactive neurotransmitter that plays a role in the trigeminal system (and elsewhere). Applications for the approval of anti-CGRP antibodies in the USA and the European Union in 2018 have been submitted.

Patients with very frequent (but still episodic, not chronic) migraine should be treated both with drugs and with supplementary non-pharmacological measures: the available types include cognitive-behavioral pain management training, behavioral therapy, and aerobic endurance sports (swimming, cycling) (e5). Further methods of documented efficacy are the Jacobson technique of progressive muscle relaxation, biofeedback, and acupuncture (e5). Homeopathy was found to be ineffective in placebo-controlled trials (14).

Tension headache

Despite their name, which is of historical origin, tension headache is not caused by muscle tension. Indeed, the IHS officially calls tension headache “tension-type headache” to avoid any implication as to their cause. The pain is typically moderately intense (Visual Analog Scale [VAS] 3), holocranial, and of a dull or pressing character. There are generally no accompanying symptoms; rarely, there may be photophobia or phonophobia.

Nearly all human beings experience headache, at least on occasion, as an appropriate physiological response to trauma or infection. This nonspecific headache, often described as pressing or thudding, is a tension headache. Its rarity already implies that it cannot be considered a disease in the strict sense. It is usually adequately treated with an analgesic drug, e.g., an NSAID. Tension headaches are considered to be a disease only if they arise spontaneously, frequently, and regularly. A distinction is drawn between episodic tension headache, occurring on fewer than 15 days per month, and chronic tension headache, occurring on 15 or more days per month. Chronic tension headache is relatively rare, affecting only 0.1–0.9% of the population, and poorly treatable.

NSAIDs are used acutely (15) and tricyclic drugs prophylactically (16, 17) in the treatment of tension headache. Competing differential diagnoses must be excluded: bruxism, unlike craniomandibular dysfunction, can be associated with headache and should be treated with a bite splint rather than with drugs. An uncorrected or inadequately corrected squint can cause permanent muscle strain and tension headache. Chronic sinusitis can cause facial pain and/or headache. Thus, in the author’s opinion, if the provisional diagnosis is chronic tension headache, but other possible causes have not yet been excluded, the patient should be referred not just to a neurologist or pain specialist, but also, whenever appropriate, to a dentist, otorhinolaryngologist, or ophthalmologist. Static problems of the cervical spine can also cause headache: the structural cause must be sought between the occiput and the third cervical vertebra (lesions below C3 do not cause headache) (4). If headaches first arise in a person over age 60 and are accompanied by visual disturbances, cranial arteritis must be ruled out.

Treatment

When tricyclic drugs are given to treat tension headache (e6), their clinical efficacy can be increased with concomitant behavioral therapy (16). Amitriptyline (note: monitor the ECG!) should be given in an extended release preparation to be taken in the early evening, at an initial dose of 25 mg and with 25 mg increments every 6–10 days up to a final dose of 75 mg. Many patients take their amitriptyline tablets each night on going to bed and are consequently very tired in the morning, especially when they take an extended release preparation. It is better to let the patient determine when the drug is best taken so as not to cause excessive fatigue. This, in turn, improves compliance. Amitriptyline drops, starting at 1 drop every evening, are easier to dose; the target dose is 30–40 drops. (1 mL of solution corresponds to 20 drops and contains 45.28 mg of amitriptyline hydrochloride, or 40 mg of amitriptyline.) Amitriptyline oxide is comparably effective (initial dose, 30 mg every evening; target dose, 90 mg) and usually better tolerated.

Trigeminal autonomic cephalalgias

Simultaneous activation of the trigeminal system and of the autonomic nervous system is a common feature of all trigeminal autonomic cephalalgias (TAC) and produces the clinical picture of short-lasting, strictly unilateral headache attacks with ipsilateral autonomic symptoms such as lacrimation, ptosis, nasal congestion or rhinorrhea, and conjunctival injection. These syndromes differ from one another in the duration and frequency of attacks (Table 3):

  • Cluster headache (CH) lasts 15–180 minutes and can occur up to 8 times per day.
  • Paroxysmal hemicranias last 2–30 minutes, with 1–20 attacks per day.
  • The pain of the SUNCT and SUNA syndromes lasts seconds (rather than minutes), with up to 200 attacks per day.
Clinical features of the trigeminal autonomic cephalalgias: a comparison of cluster headache with the related trigeminal autonomic cephalalgia syndromes*
Clinical features of the trigeminal autonomic cephalalgias: a comparison of cluster headache with the related trigeminal autonomic cephalalgia syndromes*
Table 3
Clinical features of the trigeminal autonomic cephalalgias: a comparison of cluster headache with the related trigeminal autonomic cephalalgia syndromes*

The distinction between SUNCT (shortlasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and SUNA (short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms) is academic: the autonomic symptoms consist exclusively of conjunctival injection and tearing in SUNCT, but are not narrowly defined in SUNA. Hemicrania continua, a further type of trigeminal autonomic cephalalgia, is a unilateral headache that is present all the time, rather than in attacks, and that can last weeks or months. The recognition and differentiation of these syndromes is important for therapeutic reasons, as they respond very well, and very selectively, to treatment. Another common feature of the trigeminal autonomic cephalalgias is periodicity, both circadian and circannual—most prominently seen in cluster headache. Patients with this disease need treatment only during active episodes (“clusters”), not in inactive periods. Circannual rhythmicity is seen in the rarer situation of chronic cluster headache as well (in which there are never more than 30 consecutive days without an attack over the course of 12 months): though present year round, the headaches periodically worsen (18).

Trigeminal autonomic cephalalgias are very rare in general and thus, for most of them, no reliable prevalence figures are available. Cluster headache is the most common kind, affecting an estimated 0.1% of the population; many cases probably go undiagnosed, however, as there are not many doctors with specialized experience in headache, and outpatient headache clinics are rarer than they should be. Physicians who are involved in the diagnosis and treatment of headache, including the trigeminal autonomic cephalalgias, find that activity in the field is highly rewarding, as these devastating syndromes have clearly delineated and easily recognizable clinical features and, once they are correctly diagnosed, generally respond well to treatment (19).

Pharmacotherapy

Cluster headache

Cluster headache is most effectively treated by the parenteral or intranasal route because the attacks are so brief. Subcutaneously injected sumatriptan is the agent of choice for the acute treatment of an attack. The inhalation of 100% oxygen at a very high flow rate (12 L/min) through a non-rebreather mask rapidly relieves the pain in up to 70% of cases. This can be usefully supplemented with intranasal lidocaine on the side of the pain, which is effective in up to 30% of patients.

The most rapidly effective drugs for attack prophylaxis in the short term are corticosteroids (e.g. prednisolone starting at 100 mg/d for 5–7 days, followed by a taper with a reduction by 20 mg per day) and triptans (which, if taken in the evening, can prevent nocturnal attacks). These drugs should not be taken over a prolonged period of time and must be replaced by other drugs for long-term prophylaxis. An alternative treatment with a favorable side-effect profile is local anesthetic and corticosteroid injection in the vicinity of the occipital nerve (20) on the affected side, which, in some patients, can terminate the cluster headache episode (21).

Verapamil is the drug of choice for the prevention of episodic cluster headache and for the treatment of chronic cluster headache (initial dose 80 mg tid, followed by escalation in 80 mg increments under ECG monitoring to a final dose of ca. 480 mg/d). Lithium is effective as well (initial dose one 450 mg tablet per day, with further dose increases depending on serum levels), particularly in patients with chronic cluster headache. The drug of third choice is topiramate (initial dose 25 mg/d, followed by escalation in increments of 25 mg/d up to a final dose of 100–200 mg/day). Patients with chronic cluster headache often need a combination of all three of these drugs. The last resort (22) is surgery. Among the available operative interventions, chronic electrical stimulation of the occipital nerves is sometimes useful, yet problematic because of its high complication rate (cable fracture, infection). Stimulation of the sphenopalatine ganglion (SPG) is a minimally invasive procedure with good results over both the short and the long term (23, 24). Non-invasive vagal stimulation has yielded promising results in initial clinical trials (25).

Paroxysmal hemicrania

This type of headache is rare and, unlike cluster headache and the SUNA/SUNCT syndrome, is characterized by an excellent response to indomethacin—a fact that underscores the importance of a correct differential diagnosis. Indomethacin at an initial dose of 25 mg tid, followed by escalation in 25 mg increments up to a maximal final dose of 75 mg tid, brings about rapid and complete relief of headache. Patients should take the lowest effective dose in their individual case; many do well with doses as low as 10 mg qid (individualized formulations can easily be obtained from pharmacies). Indomethacin can cause peptic ulcers, and thus a proton-pump inhibitor should always be given simultaneously to prevent this serious complication. If indomethacin alone does not suffice, gabapentin may be effective; it should be given in an increasing dose, with increments of 300 mg every 2–3 days, until the attacks cease. Doses of up to 3600 mg/d are very rarely needed, but can be given if well tolerated. Cyclo-oxygenase (COX-2) inhibitors may also be effective, but their long-term use is problematic because of the risk of heart attack and stroke. Triptans are ineffective (26). Local anesthetic blocks of pericranial nerves are ineffective, but regional anesthesia in the territory of the greater occipital nerve with local anesthetics and depot corticosteroids can be helpful (27).

SUNCT/SUNA syndrome

The individual attacks in these two types of primary headache are so short that no acute treatment is possible. At present, the most effective drug for prophylaxis is lamotrigine (28) (initial dose 25 mg, then escalation in 25 mg increments up to a final dose of ca. 100 mg/d), which can, however, cause a severe allergic rash. Other drugs that can be effective in individual cases include topiramate, gabapentin, and carbamazepine.

Hemicrania continua

Hemicrania continua, like paroxysmal hemicrania, responds well to indomethacin. One starts at a dose of 25 mg tid and increases the dose in 25 mg steps until the pain ceases or the maximum dose of 75 mg tid is reached. As in paroxysmal hemicrania, a proton-pump inhibitor must be given simultaneously to prevent peptic ulcer and hemorrhage as adverse effects of indomethacin. There is no reliably effective alternative, but gabapentin, pregabalin, and topiramate can be tried. Also as in paroxysmal hemicrania, COX-2 inhibitors and ipsilateral regional block of the greater occipital nerve may be effective (freedom from attacks is possible for an interval ranging from a few hours to several weeks).

Benign exertional headache syndromes

The common features of these syndromes are the provocation of headache by physical exertion and, usually, the sudden onset of the headache. Headaches of this kind can also occasionally arise without any preceding exertion; for this reason, and because of their suddenness, they can resemble the headache of spontaneous subarachnoid hemorrhage. The diagnosis of benign exertional headache is not securely established until this competing diagnosis has been ruled out, and only then can treatment be initiated. Further important elements of the differential diagnosis include cerebral venous sinus thrombosis, intracranial hypertension, and dissection.

This group of headache syndromes includes the following:

  • Primary exercise headache (after any physical exertion)
  • Primary cough headache (headache induced by coughing and Valsalva maneuvers)
  • Primary headache associated with sexual activity (“coital cephalalgia,” i.e., headache induced only by sexual intercourse).

No controlled therapeutic trials have been conducted, and therefore no evidence-based treatment recommendations can be given. There is, however, adequate evidence from clinical experience, case reports, and uncontrolled trials to support certain treatment strategies (29). The drug of choice is either a beta-blocker (a low dose of propranolol usually suffices) or indomethacin (29, 30). Sufferers from benign exertional headache have normal intracranial pressure, but lumbar puncture can be useful not only as part of the differential diagnostic investigation (exclusion of subarachnoid hemorrhage), but also as treatment: often, headaches of this type no longer arise once a lumbar puncture has been performed. It is sometimes even helpful if the physician uses a “traumatic” spinal needle for the lumbar puncture, with the deliberate intention of creating a small persistent leak of cerebrospinal fluid into the extradural space for therapeutic purposes. So-called atraumatic needles are thinner and less sharp, and their use generally causes no such leak.

Primary stabbing headache

This type of headache is not rare and is to be distinguished from the trigeminal autonomic cephalalgias. It consists of paroxysmal headache attacks that last only a fraction of a second or a few seconds each, occurring either singly or in a series of attacks and sometimes affecting only a circumscribed area. The attacks reach a maximum frequency of up to 100 attacks per day and recur at irregular intervals. This type of headache is more common in persons who already suffer from another type of primary headache, and the attacks can be either spontaneous or triggered, e.g., by ice cream or cold drinks. Variants of primary stabbing headache include the common jabs and jolts syndrome (randomly occurring, spatially circumscribed stabbing headache), icepick-like headache (also cold-induced), and ophthalmodynia (lancinating pains in the corner of an eye that last for several seconds). There are usually no accompanying autonomic phenomena.

This type of headache usually needs no treatment. If the attacks are very frequent (there can be up to 200 per day) and very intense, adversely affecting the patient’s overall quality of life, then treatment with indomethacin is indicated and is effective in more than 65% of cases (31, 32). The appropriate dose is 25–50 mg po bid, in combination with a proton-pump inhibitor as needed. Alternatively, gabapentin (33) (given in 300 mg increments until the headaches cease) can also be effective.

Other rare but treatable types of primary headache include hypnic (sleep-related) headache, nummular (coin-like) headache, cold-stimulus headache, and new daily persistent headache (eSupplement).

Prevalence
Headache, like dizziness, is one of the more common presenting complaints in outpatient care and in the emergency room.

Headache classification
The different major types of headache have a varying number of subtypes (migraine has 13); this explains how the IHS classification can contain more than 200 types of headache.

Headaches are divided into primary and secondary types
Primary headaches are all those that are not due to another disease. The four types of primary headache are migraine, tension headache, trigeminal autonomic cephalalgias, and group 4, “other primary headache disorders.” Secondary headaches are symptoms of another disease.

Warning symptoms
  • The initial manifestation of headache of an atypical kind
  • An atypical clinical course
  • Increasing severity of pain or changing character of pain in a patient with a known headache syndrome
  • Other neurological symptoms than aura in migraine

Chronic migraine
The term “chronic migraine” refers, by definition, to headaches that have been present on at least 15 days per month for at least 3 consecutive months, and that have met the defining criteria for migraine on at least 8 days in each month.

The treatment of migraine
The treatment of migraine has two components: acute treatment and prophylaxis. Analgesics (usually nonsteroidal anti-inflammatory drugs [NSAIDs]) or specific anti-headache drugs (triptanes) are used for acute treatment.

Drug-induced persistent headache
All analgesics, including triptans, can increase the frequency of attacks and cause drug-induced continuous headache if they are taken too frequently. It follows that analgesics, including triptans, should be taken on no more than 8–10 days per month.

Prophylaxis
Patients who regularly suffer from unusually long migraine attacks, or from more than three attacks per month, stand to benefit from prophylactic treatment. The goal is to lessen the frequency, severity, and duration of migraine attacks and to prevent drug-induced continuous headache.

Tension headache
The headache is typically moderately intense (VAS 3), holocranial, and of a dull or pressing character. There are generally no accompanying symptoms; rarely, there may be photophobia or phonophobia.

Trigeminal autonomic cephalalgias
Simultaneous activation of the trigeminal system and of the autonomic nervous system is a common feature of all trigeminal autonomic cephalalgias and produces the clinical picture of short-lasting, strictly unilateral headache attacks with ipsilateral autonomic symptoms.

Hemicrania continua
Hemicrania continua is a unilateral headache that is present all the time and that can last weeks or months.

Cluster headache
Cluster headache is the most common kind of trigeminal autonomic cephalalgia, affecting an estimated 0.1% of the population.

The treatment of cluster headache
Subcutaneously injected sumatriptan is the agent of choice for the acute treatment of an attack. The inhalation of 100% oxygen at a very high flow rate (12 L/min) through a non-rebreather mask rapidly relieves the pain in up to 70% of cases.

SUNCT/SUNA syndrome
The individual attacks in these two types of primary headache are so short that no acute treatment is possible. At present, the most effective drug for prophylaxis is lamotrigine.

Exertional headache syndromes
Headaches of this kind can arise without any preceding exertion; for this reason, and because of their suddenness, they can resemble the headache of spontaneous subarachnoid hemorrhage (SAH). The diagnosis is not established until SAH has been ruled out. Only then can treatment be initiated.

Primary stabbing headache
This type of headache is not rare and is to be distinguished from the trigeminal autonomic cephalalgias. It consists of paroxysmal headache attacks that last only a fraction of a second or a few seconds each.

Conflict of interest statement
Prof. May received lecturing and consulting fees until 2015 and has been the editor-in-chief of the journal Cephalalgia since 2016. His institution, the Universitätsklinikum Hamburg Eppendorf (Hamburg, Germany), has received third-party funding from the Chordate and Electrocore companies over the past two years in support of independent research projects that were initiated by Prof. May.


Manuscript received on 31 May 2017, revised version accepted on 20 March 2018.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Arne May

Universitätsklinikum Hamburg Eppendorf

Institut für Systemische Neurowissenschaften

Martinistr. 52, 20246 Hamburg, Germany

a.may@uke.de

Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref1718

eSupplement:
www.aerzteblatt-international.de/18m0299

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Whitmarsh TE, Coleston-Shields DM, Steiner TJ: Double-blind randomized placebo-controlled study of homoeopathic prophylaxis of migraine. Cephalalgia 1997; 17: 600–4 CrossRef MEDLINE
15.
Haag G, Evers S, May A, et al.: Selbstmedikation bei Migräne und Kopfschmerz vom Spannungstyp – Evidenzbasierte Empfehlungen der Deutschen Migräne- und Kopfschmerzgesellschaft (DMKG). Nervenheilkunde 2004; 23: 415–30.
16.
Straube A, May A, Sommer C, et al.: Therapie des episodischen und chronischen Kopfschmerz vom Spannungstyp und anderer chronischer täglicher Kopfschmerzen. In: Leitlinien für Diagnostik und Therapie in der Neurologie. New York: Thieme 2005, 513–21.
17.
Lance JW, Curran DA: Treatment of chronic tension headache. Lancet 1964; 42: 1236–9 CrossRef
18.
Jurgens TP, Koch HJ, May A: Ten years of chronic cluster – attacks still cluster. Cephalalgia 2010; 30: 1123–6 CrossRef MEDLINE
19.
Hoffmann J, May A: Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol 2018; 17: 75–83 CrossRef
20.
Ambrosini A, Vandenheede M, Rossi P, et al.: Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study. Pain 2005; 118: 92–6 CrossRef MEDLINE
21.
Leroux E, Valade D, Taifas I, et al.: Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2011; 10: 891–7 CrossRef
22.
Goadsby PJ, Schoenen J, Ferrari MD, et al.: Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia 2006; 26: 1168–70 CrossRef MEDLINE
23.
Schoenen J, Jensen RH, Lantéri-Minet M, et al.: Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia 2013; 33: 816–30 CrossRef MEDLINE PubMed Central
24.
Jürgens TP, Barloese M, May A, et al.: Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache. Cephalalgia Int J Headache 2017; 37: 423–34 CrossRef MEDLINE PubMed Central
25.
Gaul C, Diener HC, Silver N, et al.: Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia 2016; 36: 534–46 CrossRef MEDLINE PubMed Central
26.
Antonaci F, Pareja JA, Caminero AB, et al.: Chronic paroxysmal hemicrania and hemicrania continua: lack of efficacy of sumatriptan. Headache 1998; 38: 197–200 CrossRef CrossRef
27.
Goadsby PJ, Lipton RB: A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain 1997; 120: 193–209 CrossRef
28.
Cohen A, Matharu M, Goadsby P: Suggested guidelines for treating SUNCT and SUNA. Cephalalgia 2005; 25: 1200.
29.
Evers S, Goadsby P, Jensen R, et al.: Treatment of miscellaneous idiopathic headache disorders (group 4 of the IHS classification) – report of an EFNS task force. Eur J Neurol Off J Eur Fed Neurol Soc 2011; 18: 803–12 CrossRef
30.
Frese A, Rahmann A, Gregor N, et al.: Headache associated with sexual activity: prognosis and treatment options. Cephalalgia 2007; 27: 1265–70 CrossRef MEDLINE
31.
Dodick DW: Indomethacin-responsive headache syndromes. Curr Pain Headache Rep 2004; 8: 19–26 CrossRef
32.
Pareja JA, Ruiz J, de Isla C, et al.:Idiopathic stabbing headache (jabs and jolts syndrome) [see comments]. Cephalalgia 1996; 16: 93–6 CrossRef MEDLINE
33.
Franca MC, Costa AL, Maciel JA: Gabapentin-responsive idiopathic stabbing headache. Cephalalgia 2004; 24: 993–6 CrossRef MEDLINE
34.
Evers S, Goadsby PJ: Hypnic headache: clinical features, pathophysiology, and treatment. Neurology 2003; 60: 905–9 CrossRef
35.
Holle D, Naegel S, Obermann M: Hypnic headache. Cephalalgia Int J Headache 2013; 33: 1349–57 CrossRef MEDLINE
36.
May A: Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005; 366: 843–55 CrossRef
e1.
Straube A, Gaul C, Förderreuther S, et al.: Therapy and care of patients with chronic migraine: expert recommendations of the German Migraine and Headache Society/German Society for Neurology as well as the Austrian Headache Society/Swiss Headache Society. Nervenarzt 2012; 83: 1600–8 CrossRef MEDLINE
e2.
Straube A, May A, Kropp P et al.: Therapie primärer chronischer Kopfschmerzen: Chronische Migräne, chronischer Kopfschmerz vom Spannungstyp und andere chronische tägliche Kopfschmerzen. Schmerz 2008; 22: 531–34, 536–40, 542–3.
e3.
May A, Evers S, Brössner G, et al: Leitlinie zur Diagnostik, Therapie und Prophylaxe von Cluster Kopfschmerz, anderen Trigemino-Autonomen Kopfschmerzen, schlafgebundenem Kopfschmerz und idiopathisch stechenden Kopfschmerzen Nervenheilkunde 2016; 35: 137–51.
e4.
Evers S, Frese A, May A, Sixt G, Straube A: Therapie seltener idiopathischer Kopfschmerzerkrankungen Empfehlungen der Deutschen Migräne- und Kopfschmerzgesellschaft. Nervenheilkunde 2005; 24: 217–26 CrossRef
e5.
Kropp P, Meyer B, Dresler T, et al.: Relaxation techniques and behavioural therapy for the treatment of migraine: guidelines from the German Migraine and Headache Society. Schmerz 2017; 31: 433–47 CrossRef MEDLINE
e6.
AWMF: Leitlinie Kopfschmerz, episodische und chronische vom Spannungstyp und andere chronische tägliche Kopfschmerzen, Therapie. www.awmf.org/leitlinien/detail/ll/030-077.html (last accessed on 21 March 2018).
Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf (UKE): Prof. Dr. med. Arne May
Important websites
The main clinical features of primary headache syndromes
The main clinical features of primary headache syndromes
Table 1
The main clinical features of primary headache syndromes
Epidemiological data on primary headache types*
Epidemiological data on primary headache types*
Table 2
Epidemiological data on primary headache types*
Clinical features of the trigeminal autonomic cephalalgias: a comparison of cluster headache with the related trigeminal autonomic cephalalgia syndromes*
Clinical features of the trigeminal autonomic cephalalgias: a comparison of cluster headache with the related trigeminal autonomic cephalalgia syndromes*
Table 3
Clinical features of the trigeminal autonomic cephalalgias: a comparison of cluster headache with the related trigeminal autonomic cephalalgia syndromes*
Tips on treatment
1.Headache Classification Committee of the International Headache Society (IHS): The international classification of headache disorders, 3rd edition (beta version). Cephalalgia Int J Headache 2013; 33: 629–808 CrossRef MEDLINE
2. May A, Straube A, Peikert A, et al.: Diagnostik und apparative Zusatzuntersuchungen bei Kopfschmerzen. Stuttgart, New York: Thieme, 2008.
3. Hoffmann J, May A: Ice-pick-headache und andere seltene Kopfschmerzformen. InFo Neurol Psychiatr 2016; 18: 44–50 CrossRef
4. Bogduk N, Govind J: Cervicogenic headache: an assessment of the evidence on clinical diagnosis, invasive tests, and treatment. Lancet Neurol 2009; 8: 959–68 CrossRef
5. Kelman L. The aura: a tertiary care study of 952 migraine patients. Cephalalgia 2004; 24: 728–34 CrossRef MEDLINE
6. May A, Schulte LH: Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol 2016; 12: 455–64 CrossRef MEDLINE
7. Evers S, Rahmann A, Vollmer-Haase J, et al.: Treatment of headache with botulinum toxin A-a review according to evidence-based medicine criteria. Cephalalgia 2002; 22: 699–710 CrossRef MEDLINE
8. Evers S, May A, Fritsche G, et al.: Akuttherapie und Prophylaxe der Migräne. Nervenheilkunde 2008; 27: 933–49 CrossRef
9.Diener HC, Limmroth V: Medication-overuse headache: a worldwide problem. Lancet Neurol 2004; 3: 475–83 CrossRef
10. Rozen TD: Migraine headache: immunosuppressant therapy. Curr Treat Options Neurol 2002; 4: 395–401 CrossRef
11. Tso AR, Goadsby PJ: Anti-CGRP monoclonal antibodies: the next era of migraine prevention? Curr Treat Options Neurol 2017; 19: 27 CrossRef MEDLINE PubMed Central
12.Silberstein SD, Dodick DW, Bigal ME, et al.: Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med 2017; 377: 2113–22 CrossRef MEDLINE
13.Tepper S, Ashina M, Reuter U, et al.: Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017; 16: 425–34 CrossRef
14.Whitmarsh TE, Coleston-Shields DM, Steiner TJ: Double-blind randomized placebo-controlled study of homoeopathic prophylaxis of migraine. Cephalalgia 1997; 17: 600–4 CrossRef MEDLINE
15.Haag G, Evers S, May A, et al.: Selbstmedikation bei Migräne und Kopfschmerz vom Spannungstyp – Evidenzbasierte Empfehlungen der Deutschen Migräne- und Kopfschmerzgesellschaft (DMKG). Nervenheilkunde 2004; 23: 415–30.
16.Straube A, May A, Sommer C, et al.: Therapie des episodischen und chronischen Kopfschmerz vom Spannungstyp und anderer chronischer täglicher Kopfschmerzen. In: Leitlinien für Diagnostik und Therapie in der Neurologie. New York: Thieme 2005, 513–21.
17.Lance JW, Curran DA: Treatment of chronic tension headache. Lancet 1964; 42: 1236–9 CrossRef
18.Jurgens TP, Koch HJ, May A: Ten years of chronic cluster – attacks still cluster. Cephalalgia 2010; 30: 1123–6 CrossRef MEDLINE
19.Hoffmann J, May A: Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol 2018; 17: 75–83 CrossRef
20.Ambrosini A, Vandenheede M, Rossi P, et al.: Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study. Pain 2005; 118: 92–6 CrossRef MEDLINE
21.Leroux E, Valade D, Taifas I, et al.: Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2011; 10: 891–7 CrossRef
22.Goadsby PJ, Schoenen J, Ferrari MD, et al.: Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia 2006; 26: 1168–70 CrossRef MEDLINE
23.Schoenen J, Jensen RH, Lantéri-Minet M, et al.: Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia 2013; 33: 816–30 CrossRef MEDLINE PubMed Central
24.Jürgens TP, Barloese M, May A, et al.: Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache. Cephalalgia Int J Headache 2017; 37: 423–34 CrossRef MEDLINE PubMed Central
25.Gaul C, Diener HC, Silver N, et al.: Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia 2016; 36: 534–46 CrossRef MEDLINE PubMed Central
26.Antonaci F, Pareja JA, Caminero AB, et al.: Chronic paroxysmal hemicrania and hemicrania continua: lack of efficacy of sumatriptan. Headache 1998; 38: 197–200 CrossRef CrossRef
27.Goadsby PJ, Lipton RB: A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain 1997; 120: 193–209 CrossRef
28.Cohen A, Matharu M, Goadsby P: Suggested guidelines for treating SUNCT and SUNA. Cephalalgia 2005; 25: 1200.
29.Evers S, Goadsby P, Jensen R, et al.: Treatment of miscellaneous idiopathic headache disorders (group 4 of the IHS classification) – report of an EFNS task force. Eur J Neurol Off J Eur Fed Neurol Soc 2011; 18: 803–12 CrossRef
30.Frese A, Rahmann A, Gregor N, et al.: Headache associated with sexual activity: prognosis and treatment options. Cephalalgia 2007; 27: 1265–70 CrossRef MEDLINE
31.Dodick DW: Indomethacin-responsive headache syndromes. Curr Pain Headache Rep 2004; 8: 19–26 CrossRef
32.Pareja JA, Ruiz J, de Isla C, et al.:Idiopathic stabbing headache (jabs and jolts syndrome) [see comments]. Cephalalgia 1996; 16: 93–6 CrossRef MEDLINE
33.Franca MC, Costa AL, Maciel JA: Gabapentin-responsive idiopathic stabbing headache. Cephalalgia 2004; 24: 993–6 CrossRef MEDLINE
34.Evers S, Goadsby PJ: Hypnic headache: clinical features, pathophysiology, and treatment. Neurology 2003; 60: 905–9 CrossRef
35.Holle D, Naegel S, Obermann M: Hypnic headache. Cephalalgia Int J Headache 2013; 33: 1349–57 CrossRef MEDLINE
36.May A: Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005; 366: 843–55 CrossRef
e1.Straube A, Gaul C, Förderreuther S, et al.: Therapy and care of patients with chronic migraine: expert recommendations of the German Migraine and Headache Society/German Society for Neurology as well as the Austrian Headache Society/Swiss Headache Society. Nervenarzt 2012; 83: 1600–8 CrossRef MEDLINE
e2. Straube A, May A, Kropp P et al.: Therapie primärer chronischer Kopfschmerzen: Chronische Migräne, chronischer Kopfschmerz vom Spannungstyp und andere chronische tägliche Kopfschmerzen. Schmerz 2008; 22: 531–34, 536–40, 542–3.
e3. May A, Evers S, Brössner G, et al: Leitlinie zur Diagnostik, Therapie und Prophylaxe von Cluster Kopfschmerz, anderen Trigemino-Autonomen Kopfschmerzen, schlafgebundenem Kopfschmerz und idiopathisch stechenden Kopfschmerzen Nervenheilkunde 2016; 35: 137–51.
e4. Evers S, Frese A, May A, Sixt G, Straube A: Therapie seltener idiopathischer Kopfschmerzerkrankungen Empfehlungen der Deutschen Migräne- und Kopfschmerzgesellschaft. Nervenheilkunde 2005; 24: 217–26 CrossRef
e5. Kropp P, Meyer B, Dresler T, et al.: Relaxation techniques and behavioural therapy for the treatment of migraine: guidelines from the German Migraine and Headache Society. Schmerz 2017; 31: 433–47 CrossRef MEDLINE
e6. AWMF: Leitlinie Kopfschmerz, episodische und chronische vom Spannungstyp und andere chronische tägliche Kopfschmerzen, Therapie. www.awmf.org/leitlinien/detail/ll/030-077.html (last accessed on 21 March 2018).