Of all the painful states that afflict humans, headache is undoubtedly the most frequent and rivals backache as one of the most common reasons for seeking medical help. In fact, there are so many cases of headache that dedicated headache clinics have been established in many medical centers. In addition to its frequency in general practice, many headaches are caused by medical rather than neurologic diseases and the subject is the legitimate concern of the general physician. Yet there is always the question of intracranial disease so that it is difficult to approach the subject without knowledge of neurology.
Why so many pains are centered in the head is a question of some interest. Several explanations come to mind. For one thing, the face and scalp are more richly supplied with pain receptors than many other parts of the body, perhaps to protect the precious contents of the skull. Also, the nasal and oral passages, the eye, and the ear—all delicate and highly sensitive structures—reside here and must be protected; when affected by disease, each is capable of inducing pain in its own way. Finally, there is great concern by patients about what happens to the head perhaps more than other parts of the body because headache raises the specter of brain tumor or other cerebral disease.
Semantically, the term headache encompasses all aches and pains located in the head, but in practice, its application is restricted to discomfort in the region of the cranial vault. Facial, lingual, and pharyngeal pains are discussed in the latter part of this chapter and separately in Chap. 44, because they pertain to the cranial nerves.
In the introductory chapter on pain, reference was made to the necessity, in dealing with any painful state, of determining its quality, severity, location, duration, and time course as well as the conditions that produce, exacerbate, or relieve it. In the case of headache, a detailed history following these lines will determine the diagnosis more often than will the physical examination or imaging. Nevertheless, a few aspects of the examination are worth emphasizing. For example, auscultation of the skull may rarely disclose a bruit (with large arteriovenous malformations); palpation may disclose the tender, hardened or elevated arteries of temporal arteritis; sensitive areas overlying a cranial metastasis or an inflamed paranasal sinus may be apparent; or there may be a tender occipital nerve. Examination of neck flexion may reveal meningitis; however, apart from such special instances, examination of the head itself, although necessary, seldom discloses the diagnosis.
The quality of cephalic pain is essential to diagnosis but the sensation may be difficult for the patient to describe. When asked to compare the pain to some other sensory experience, the patient may allude to tightness, aching, pressure, burning, bursting, sharpness, or stabbing. Among the most important aspects is whether the headache is pulsatile, usually implying migraine, but one must keep in mind that patients sometimes use the word throbbing to refer to a waxing and waning of the headache without any relation to the pulse, or use the term to transmit the severity of pain.
Similarly, statements about the intensity of the pain are inherently subjective, as they reflect as much the patient’s temperament, attitudes, and customary ways of experiencing and reacting to pain. One useful index of severity is the degree to which the pain has incapacitated the patient. A severe migraine attack seldom allows the migraineur to perform the day’s work. Other rough indices of the severity of headache are its propensity to awaken the patient from sleep or to prevent sleep, and autonomic reactions to the pain such as sweating and tachycardia. The most intense cranial pains are those associated with meningitis and subarachnoid hemorrhage, which can have grave consequences, but also migraine, cluster headache, or tic douloureux that do not have the same implications.
Data regarding the location of a headache is informative. Migraine headache is unilateral in two-thirds of attacks and is commonly associated with nausea, vomiting, and sensitivity to light, sound, and smells. Inflammation of an extracranial artery from temporal arteritis causes pain localized to the site of the vessel. Lesions of the paranasal sinuses, teeth, eyes, and upper cervical vertebrae induce a less sharply localized pain but still one that is referred to a certain region, usually the forehead or maxilla or around the eyes. Intracranial lesions in the posterior fossa generally cause pain in the occipitonuchal region and usually are homolateral if the lesion is one-sided. Supratentorial lesions induce frontotemporal pain, or approximate the site of the lesion. Localization, however, may also be deceiving. Pain in the frontal regions may be caused by such diverse lesions and mechanisms as glaucoma, sinusitis, thrombosis of the vertebral or basilar artery, pressure on the tentorium, and increased intracranial pressure. Similarly, ear pain may signify disease of the ear itself, but as often, it is referred from other regions, such as the throat, cervical muscles, spine, or structures in the posterior fossa. Periorbital and supraorbital pain, while usually indicative of local disease, may reflect dissection of the cervical portion of the internal carotid artery. Headaches localized to the vertex or biparietal regions are infrequent and should raise the suspicion of sphenoid or ethmoid sinus disease or thrombosis of the superior sagittal venous sinus.
The mode of onset, the variation of the pain over time, and duration of the headache, with respect both to a single attack and to the profile of the headache over a period of years, are also useful data. At one extreme, the headache of subarachnoid hemorrhage (caused by a ruptured aneurysm) occurs as an abrupt attack that attains its maximal severity in a matter of seconds or minutes, or, in the case of meningitis, it may come on more gradually, over several hours or days. Simulating the rapid onset, severe headache of subarachnoid hemorrhage are a group of “thunderclap headaches” of diverse causes but principally cerebral venous thrombosis and vasospasm syndromes. Brief sharp pain, lasting a few seconds, in the eyeball (ophthalmodynia) or cranium (“ice-pick” pain) and “ice-cream headache” caused by pharyngeal cooling is more common in migraineurs and are significant only by reason of their benignity.
With regard to characteristic temporal patterns, migraine of the typical type usually has its onset in the early morning hours or in the daytime, reaches its peak of severity over several to 30 min, and lasts, unless treated, for 4 to 24 h, occasionally longer. Often, it is terminated by sleep. A migrainous patient having several attacks per week usually proves to have a chronic form of migraine or a combination of migraine and analgesic “overuse headache,” meaning that the headache returns when the effect of the drug has worn off, or rarely, some unexpected intracranial lesion. By contrast, cluster headache is characterized by the occurrence of unbearably severe unilateral orbitotemporal pain coming on within 1 or 2 h after falling asleep or at predictable times during the day and recurring nightly or daily for a period of several weeks to months; usually an individual attack of “cluster” dissipates in 30 to 45 min but may occasionally last several hours. The headache of intracranial tumor may appear at any time of the day or night; it may interrupt sleep, vary in intensity, and last a few minutes to hours as the tumor raises intracranial pressure. With posterior fossa masses, the headache tends to be worse in the morning, on awakening. Tension headaches (now called “tension-type headache”) can persist with varying intensity for weeks to months or even longer; when such headaches are protracted, there is often an associated depressive illness. In general, headaches that have recurred regularly for many years prove to be migraine or tension in type.
The relationship of headache to certain biologic events and also to certain precipitating, aggravating, or relieving factors can be of great significance in diagnosis. Headaches that occur regularly in the premenstrual period are usually generalized and mild in degree, but attacks of migraine may also occur at this time (catamenial migraine). Headaches that have their origin in cervical spine disease are most typically intense after a period of inactivity, such as a night’s sleep, and the first movements of the neck are stiff and painful. Headache, or more often face ache, from infection of the nasal sinuses may appear upon awakening or in midmorning and is characteristically worsened by stooping and changes in atmospheric pressure; there is associated midfrontal or maxillary tenderness. Eyestrain after long-sustained periods of reading, or exposure to the glare of video displays, may be associated with head pain but it is transient and not an important cause of headache. In certain individuals, alcohol, intense exercise (such as weight lifting), stooping, straining, coughing, and sexual intercourse are known to initiate a bursting (thunderclap) headache, lasting a few seconds to minutes. If a headache is made worse by sudden movement or by coughing or straining, an intracranial source is tentatively suggested. Migraine often occurs several hours or a day following a period of intense activity and stress (“weekend,” or “letdown” migraine). Some patients have discovered that their migraine is relieved momentarily by gentle compression of the carotid or superficial temporal artery on the painful side, and others report that the carotid near the angle of the jaw is tender during the headache. Pain that is noticed when the scalp is stroked in combing or fixing the hair (allodynia) is common in migraine but could be a symptom of inflammation of the temporal arteries (temporal arteritis). Certain medications, most vasodilators such as nitroglycerin and dipyridamole but also monosodium glutamate, are apt to cause headaches. The headaches that follow a period or excessive alcohol (hangover) or a concussion are well known. In many of these instances, a propensity for migraine may create a susceptibility to an induced headache.
Pain-Sensitive Cranial Structures
Our understanding of headache has been augmented by observations made during operations on the brain by Ray and Wolff. These observations inform us that only certain cranial structures are sensitive to noxious stimuli: (1) skin, subcutaneous tissue, muscles, extracranial arteries, and external periosteum of the skull; (2) the delicate structures of the eye, ear, nasal cavities, and paranasal sinuses; (3) intracranial venous sinuses and their large tributaries because they are intradural; (4) parts of the dura at the base of the brain and the arteries within the dura, particularly the proximal parts of the anterior and middle cerebral arteries and the intracranial segment of the internal carotid artery; (5) the middle meningeal and superficial temporal arteries; and (6) the first three cervical nerves and cranial nerves as they pass through the dura. Interestingly, pain is practically the only sensation produced by stimulation of these structures. Much of the pia-arachnoid, the parenchyma of the brain, and the ependyma and choroid plexuses lack sensitivity.
The reference sites of pain from the aforementioned structures are important in understanding the genesis of cranial pain. Pain that arises from distention of the middle meningeal artery is projected to the back of the eye and temporal area. Pain from the intracranial segment of the internal carotid artery and proximal parts of the middle and anterior cerebral arteries is felt in the eye and orbitotemporal regions. The pathways whereby cephalic sensory stimuli are transmitted to the central nervous system (CNS) are the trigeminal nerves, particularly their first and, to some extent, second divisions, which convey impulses from the forehead, orbit, anterior and middle fossae of the skull, and the upper surface of the tentorium. The sphenopalatine branches of the facial nerve convey impulses from the nasoorbital region. The ninth and tenth cranial nerves and the first three cervical nerves transmit impulses from the inferior surface of the tentorium and all of the posterior fossa. The tentorium roughly demarcates the trigeminal from the cervical–vagal–glossopharyngeal innervation zones. The central sensory connections, which ascend through the brainstem or the cervical spinal cord and brainstem to the thalamus, are described in Chaps. 7 and 8. Sympathetic fibers from the three cervical ganglia and parasympathetic fibers from the sphenopalatine and otic ganglia are mixed with the trigeminal and other sensory fibers. These assume importance in certain headache syndromes considered further on.
There may be local tenderness of the scalp at the site of the referred pain. Dental or temporomandibular joint pain impulses are carried by the second and third divisions of the trigeminal nerve. With the exception of the cervical portion of the internal carotid artery, from which pain is referred to the eyebrow and supraorbital region, and the upper cervical spine, from which pain may be referred to the occiput, pain from disease in extracranial parts of the body is not referred to the head. There are, however, rare instances of angina pectoris that may produce discomfort at the cranial vertex or adjacent sites and, of course, in the jaw.
Mechanisms of Cranial Pain
The studies of Ray and Wolff demonstrated that relatively few mechanisms are operative in the genesis of cranial pain. More specifically, intracranial mass lesions cause headache if they deform, displace, or exert traction on vessels and dural structures at the base of the brain, and this may happen long before intracranial pressure rises. In fact, artificially raising the intraspinal and intracranial pressure by the subarachnoid or intraventricular injection of sterile saline solution does not consistently result in headache. This has been interpreted to mean that raised intracranial pressure does not cause headache—a questionable conclusion when one considers the relief of headache in some patients that follows lumbar puncture and lowering of the cerebrospinal fluid (CSF) pressure, particularly after subarachnoid hemorrhage. Actually, most patients with high intracranial pressure complain of bioccipital and bifrontal headaches that fluctuate in severity.
Dilatation of intracranial or extracranial arteries (and possibly sensitization of these vessels), of whatever cause, is likely to produce headache. The headaches that follow seizures and ingestion of alcohol are probably all caused by cerebral vasodilatation. Nitroglycerin, nitrites in cured meats (“hot-dog headache”), and monosodium glutamate in some foods may cause headache by the same mechanism. It is possible that the throbbing or steady headache that accompanies febrile illnesses has a vascular origin as well; it is likely that the increased pulsation of meningeal vessels activates pain-sensitive structures within their walls or around the base of the brain. Febrile headache may be generalized or predominate in the frontal or occipital regions and is relieved on one side by carotid or superficial temporal artery compression and on both sides by jugular vein compression. Like migraine, it is also increased by shaking the head. Certain systemic infectious agents, enumerated further on, have a tendency to cause severe headache.
A similar mechanism may be operative in the severe, bilateral, throbbing headaches associated with extremely rapid rises in blood pressure, as occurs with pheochromocytoma, malignant hypertension, sexual activity, and in patients being treated with monoamine oxidase inhibitors. Mild to moderate degrees of chronic hypertension, however, do not cause headaches despite a popular notion to the contrary. So-called cough and exertional headaches may also have their basis in the distention of intracranial vessels.
For many years, following the investigations of Harold Wolff, the headache of migraine was attributed to dilatation of the extracranial arteries. Now, it appears that this is not a constant relationship and that the headache is of complex intracranial as much as extracranial origin, perhaps related to the sensitization of blood vessels and their surrounding structures. Activation of the trigeminovascular system (the trigeminal nerves and the blood vessels they supply), leading to an inflammatory response that is generated by local neural mechanisms, “neurogenic inflammation,” has also been assigned a role in migraine headache. These and other theories of causation are summarized by Cutrer and discussed further on in this chapter in the section on migraine.
With regard to cerebrovascular diseases causing head pain, the extracranial temporal and occipital arteries, when involved in giant cell arteritis (cranial or “temporal” arteritis), give rise to severe, persistent headache, at first localized on the scalp and then more diffuse. Most strokes caused by vascular occlusion do not cause head pain. However, with occlusion or dissection of the vertebral artery, there may be pain in the upper neck or postauricular area; basilar artery thrombosis causes pain to be projected to the occiput and sometimes to the forehead; and the ipsilateral eye and brow, and the forehead above it are the most common sites of projected pain from dissection of the carotid artery and occlusion of the stem of the middle cerebral arteries. Expanding intracranial aneurysms of the posterior communicating or distal internal carotid arteries very often cause pain projected to the eye. The distinctive headache caused by aneurysmal rupture is mentioned below and in a separate section later in the chapter.
Infection or blockage of paranasal sinuses is accompanied by pain over the affected maxillary or frontal sinuses. Usually it is associated with tenderness of the skin and cranium in the same distribution. Pain from the ethmoid and sphenoid sinuses is localized deep in the midline behind the root of the nose or occasionally at the vertex (especially with disease of the sphenoid sinus). The mechanism in these cases involves changes in pressure and irritation of pain-sensitive sinus walls.
With frontal and ethmoidal sinusitis, the pain tends to be worse on awakening and gradually subsides when the patient is upright; the opposite pertains with maxillary and sphenoidal sinusitis. These relationships are believed to disclose their mechanism; pain is ascribed to filling of the sinuses and its relief to their emptying, induced by the dependent position of the ostia. Bending over intensifies the pain by causing changes in pressure, as does blowing the nose and air travel, especially on descent, when the relative pressure in the blocked sinus rises. Sympathomimetic drugs, such as phenylephrine hydrochloride, which reduce swelling and congestion, tend to relieve the pain. However, the pain may persist after all purulent secretions have disappeared, probably because of persistent inflammation of the membranes, or blockage of the orifices and dissipation of air from the blocked sinus, so called vacuum sinus headaches.
Headache of ocular origin, located as a rule in the orbit, forehead, or temple, is of the steady, aching type and tends to follow prolonged use of the eyes in close work. However, cranial pain is too frequently attributed to ocular causes, particularly if the external appearance of the sclera and conjunctiva are normal. The main faults are hypermetropia and astigmatism (rarely myopia), which result in sustained contraction of extraocular as well as frontal, temporal, and even occipital muscles. In the uncommon and overemphasized circumstance of a refractive error causing headache, correction rapidly ameliorates the headache. Traction on the extraocular muscles or the iris during eye surgery evokes pain. Patients who develop diplopia from neurologic causes or are forced to use one eye because the other has been occluded by a patch often complain of frontal headache. Another mechanism is involved in iridocyclitis and in acute angle closure glaucoma, in which raised intraocular pressure causes steady, aching pain in the region of the eye, radiating to the forehead. When acute angle closure glaucoma causes headache, the sclera is invariably red. Dilating the pupil risks precipitating angle closure glaucoma, a situation that can be reversed by the administration of pilocarpine 1 percent drops.
Headaches that accompany disease of ligaments, muscles, and apophysial joints in the upper part of the cervical spine are referred to the occiput and nape of the neck on the same side and sometimes to the temple and forehead. These headaches have been reproduced by the injection of hypertonic saline solution into the affected ligaments, muscles, and facet joints and are comparable to the regions of sclerotogenous referred pain that is discussed in Chap. 7. Such pains are especially frequent in late life because of the prevalence of degenerative changes in the cervical spine and tend also to occur after whiplash injuries or other forms of sudden flexion, extension, or torsion of the head on the neck. If the pain is arthritic in origin, the first movements after the individual has been still for some hours are stiff and painful. The pain of fibromyalgia, a controversial entity, is characterized by tender areas near the cranial insertion of cervical and other muscles. There are no pathologic data as to the nature of these vaguely palpable and tender regions, and it is uncertain whether the pain actually arises in them. They may represent only the deep tenderness felt in the region of referred pain or the involuntary secondary protective spasm of muscles. Massage of muscles, heat, and injection of the tender spots with local anesthetic has unpredictable effects but relieves the pain in some cases. Unilateral occipital headache is often misinterpreted as occipital neuralgia (see further on).
The headache of meningeal irritation (usually due to infection or hemorrhage) is typically acute in onset, usually severe, generalized, deep seated, constant, and associated with stiffness of the neck, particularly on forward bending of the neck. It has been ascribed to increased intracranial pressure; indeed, the withdrawal of CSF may afford some relief. However, dilatation and inflammation of meningeal vessels and the chemical irritation of pain receptors in the large vessels and meninges by endogenous chemical agents, particularly serotonin and plasma kinins, are probably more important factors in the production of pain and spasm of the neck extensors. In the chemically induced meningitis from rupture of an epidermoid cyst, for example, the spinal fluid pressure is usually normal, but the headache is severe. Meningeal irritation or inflammation may also be chronic and have as its main feature a concurrently ongoing headache.
A distinctive type of headache is produced by aneurysmal subarachnoid hemorrhage; it is very intense and very sudden in onset and is usually associated with vomiting and neck stiffness. Other causes of an identical syndrome discussed further on, of what has been called “thunderclap headache,” simulate this disease (see Chap. 33). Among them are a type of diffuse cerebrovascular spasm, spontaneous or the result of sympathomimetic drugs, extracranial vascular dissection of the carotid or vertebral arteries, and cerebral venous thrombosis. There are also varieties of exertional headaches, noted below, that cause the thunderclap pattern.
Lumbar puncture (LP) and spontaneous low CSF pressure headache, as elaborated in Chap. 2, is characterized by a steady occipitonuchal and frontal pain coming on within a few minutes after arising from a recumbent position (orthostatic headache) and is relieved within a minute or two by lying down. Its cause is a persistent leakage of CSF into the lumbar tissues through the needle track, or a tear of the meninges that may be spontaneous or induced by spinal trauma. The CSF pressure is low (often zero in the lateral decubitus position), and installation of an epidural “blood patch” relieves the headache. Usually this type of headache is increased by compression of the jugular veins but is unaffected by digital obliteration of the carotid artery. It is likely that, in the upright position, a low intraspinal and negative intracranial pressure permits caudal displacement of the brain, with traction on dural attachments and dural sinuses. Pannullo and colleagues, with MRI, have demonstrated this downward displacement of the cranial contents. “Spontaneous” low-pressure headache may follow a cough, sneeze, strain, or athletic injury, sometimes as a result of rupture of the arachnoid sleeve along a nerve root (see “Spontaneous Intracranial Hypotension” in Chap. 29). Less frequently, LP is complicated by severe stiffness of the neck and pain over the back of the neck and occiput (see “Lumbar Puncture Headache” in Chap. 2); a second spinal tap in some instances discloses slight pleocytosis but no decrease in glucose—a sterile meningitis. This benign reaction must be distinguished from the rare occurrence of meningitis caused by introduction of bacteria through a rent in the meninges that has allowed both escape of spinal fluid and ingress of bacteria.
Headaches that are aggravated by lying down or lying on one side occur with acute and chronic subdural hematoma and with some brain masses, particularly those in the posterior fossa. The headache of subdural hematoma, when it occurs, is dull and unilateral, perceived over most of the affected side of the head. The global and nuchal headaches of idiopathic intracranial hypertension (pseudotumor cerebri) are also generally worse in the supine position (Chap. 29). In all these states of raised intracranial pressure, headaches are typically worse in the early morning hours after a long period of recumbency. Further on, we discuss the relative infrequency of headache as a result of brain tumor.
Exertional headaches, for example those that are associated with sexual activity or weight lifting, are usually benign but they are sometimes related to pheochromocytoma, arteriovenous malformation, or other intracranial lesions, in addition to the aforementioned subarachnoid hemorrhage from ruptured aneurysm and arterial dissection. The same usually benign nature applies to headaches induced by stooping and at worst, are accounted for by sinus infection but there are exceptions and subdural hematoma is a known cause (see further on).
PRINCIPAL VARIETIES OF IDIOPATHIC HEADACHE
The clinician’s first goal when confronted with a patient with cranial pain is to determine if the headache is primary, in which head pain is the only identifiable disease, or if it is a secondary cranial pain. The main primary headache syndromes are migraine, tension-type headache, cluster headache, and the trigeminal–sympathetic migraine variants of migraine or cluster. These primary headache disorders tend to be chronic, recurrent, and unattended by other symptoms and signs of neurologic disease. Familiarity with the variety of symptoms, temporal profiles, and accompanying features of the primary headache disorders, and the proclivity for many of them to be familial, assist in identifying them from the patient’s description. There should be little difficulty in recognizing the secondary headaches of diseases such as glaucoma, purulent sinusitis, subarachnoid hemorrhage, and bacterial or viral meningitis provided that these sources of headache are kept in mind. A fuller account of these types of “secondary” headache syndromes is given in later chapters of the book, where the underlying diseases are described. All other headaches that by their localization, quality of pain, and precipitating characteristics do not conform to one of the primary types should be suspected of being symptomatic of a cranial, cervical, or systemic disorder. Nonetheless, in many instances no such underlying cause will be found after investigation.
The following broad categories of headaches should be considered (Table 9-1). In general, the classification of these headaches and other types of craniofacial pain follow the plan outlined by the International Headache Society (see http://www.ihs-classification.org/en).
Table 9-1COMMON TYPES OF HEADACHE ||Download (.pdf) Table 9-1COMMON TYPES OF HEADACHE
|TYPE ||SITE ||AGE AND SEX ||CLINICAL CHARACTERISTICS ||DIURNAL PATTERN ||LIFE PROFILE ||PROVOKING FACTORS ||ASSOCIATED FEATURES ||TREATMENT |
|Migraine without aura (common migraine) ||Frontotemporal ||Adolescents, young to middle-aged adults, sometimes children, more common in women ||Throbbing (pulsatile); worse behind one eye or ear ||Upon awakening or later in day ||Irregular intervals, weeks to months ||Bright light, noise, tension, alcohol ||Nausea and vomiting in some cases ||Triptans, ergotamine, nonsteroidal antiinflammatory agents |
| ||Uni- or bilateral || ||Becomes dull ache and generalized ||Duration: 4–24 h in most cases, sometimes longer ||Tends to decrease in middle age and during pregnancy ||Relieved by darkness and sleep || ||Propranolol or amitriptyline for prevention |
| || || ||Scalp sensitive || || || || || |
|Migraine with aura (neurologic migraine) ||Same as above ||Same as above ||Same as above ||Same as above ||Same as above ||Same as above ||Scintillating lights, visual loss, and scotomas ||Same as above |
| || || ||Family history frequent || || || ||Unilateral paresthesias, weakness, dysphasia, vertigo, rarely confusion || |
|Cluster (histamine headache, migrainous neuralgia) ||Orbitotemporal ||Adolescent and adult males (90%) ||Intense, nonthrobbing ||Usually nocturnal, 1–2 h after falling asleep ||Nightly or daily for several weeks to months ||Alcohol in some ||Lacrimation ||O2, sumatriptan, ergotamine before anticipated attack |
| ||Unilateral || || ||Occasionally diurnal ||Recurrence after many months or years || ||Stuffed nostril ||Corticosteroids, verapamil, valproate, and lithium in recalcitrant cases |
| || || || || || || ||Rhinorrhea || |
| || || || || || || ||Injected conjunctivum || |
| || || || || || || ||Ptosis || |
|Tension headaches ||Generalized ||Mainly adults, both sexes, more common in women ||Pressure (nonthrobbing), tightness, aching ||Continuous, variable intensity, for days, weeks, or months ||One or more periods of months to years ||Fatigue and nervous strain ||Depression, worry, anxiety ||Antianxiety and antidepressant drugs |
|Meningeal irritation (meningitis, subarachnoid hemorrhage) ||Generalized, or bioccipital, or bifrontal ||Any age, both sexes ||Intense, steady deep pain, may be worse in neck ||Rapid evolution—minutes to hours ||Single episode ||None ||Neck stiff on forward bending ||For meningitis or bleeding (see text) |
| || || || || || || ||Kernig and Brudzinski signs || |
|Brain tumor ||Unilateral or generalized ||Any age, both sexes ||Variable intensity ||Lasts minutes to hours; worse in early A.M., increasing severity ||Once in a lifetime: weeks to months ||None ||Papilledema ||Corticosteroids |
| || || ||May awaken patient || || ||Sometimes position ||Vomiting ||Mannitol |
| || || ||Steady pain || || || ||Impaired mentation ||Treatment of tumor |
| || || || || || || ||Seizures || |
| || || || || || || ||Focal signs || |
|Temporal arteritis ||Unilateral or bilateral, usually temporal ||Older than 50 years, either sex ||Throbbing, then persistent aching and burning, arteries thickened and tender ||Intermittent, then continuous ||Persists for weeks to months ||None ||Loss of vision ||Corticosteroids |
| || || || || || || ||Polymyalgia rheumatica || |
| || || || || || || ||Fever, weight loss, increased sedimentation rate, jaw claudication || |
Migraine is a highly prevalent and largely familial disorder characterized by periodic, commonly unilateral, usually pulsatile headaches that often begin in childhood, adolescence, or early adult life and recurs with diminishing frequency during advancing years.
Two closely related clinical syndromes have been identified, the first called migraine with aura and the second, migraine without aura (terminology of the International Headache Society). For many years, the first syndrome was referred to as classic or neurologic migraine and the second as common migraine. Individuals may experience both types over their lives. The ratio of classic to common migraine is 1:5. Either type may be preceded by vague premonitory changes in mood and appetite. Migraine with aura is ushered in by a disturbance of nervous function, most often visual, followed in a few minutes to hours by hemicranial (or, in about one-third of cases, bilateral) headache, nausea, and sometimes vomiting, all of which last for hours or as long as a day or more. Migraine without aura is characterized by an unheralded onset over minutes or longer of increasing hemicranial headache or, less often, by generalized headache with or without nausea and vomiting, which then follows the same temporal pattern as the migraine with aura. Sensitivity to light, noise, and often smells (photophobia, phono- or sonophobia, and osmophobia) attends both types, and intensification with movement of the head is common. If the pain is severe, the patient prefers to lie down in a quiet, darkened room and tries to sleep. The hemicranial and the throbbing (pulsating) aspects of migraine are its most characteristic features in comparison to other headache types. Each patient displays a proclivity for the pain to affect one side or the other of the cranium, but not exclusively, so that some bouts are on the other side or on both sides.
The heritable nature of migraine is apparent from its occurrence in several members of the family of the same and successive generations in 60 to 80 percent of cases; the familial frequency of common migraine is slightly lower. Twin and sibling studies have not revealed a consistent mendelian pattern in either the classic or common form. Certain rare forms of migraine, such as familial hemiplegic migraine, appear to be monogenic disorders but the role of these genes, most of which code for ion channels, in all forms of migraine is still speculative.
Migraine, with or without aura, is a remarkably common condition. A study by Stewart and colleagues in the United States showed differences in the prevalence of migraine between individuals of white, African, and Asian origin of approximately 20, 16, and 9 percent, respectively, among women, and 9, 7, and 4 percent for men (see also Lipton et al). One-third of migraineurs have more than three attacks monthly if untreated and many require bed rest or severe curtailment of daily activities. Migraine may have its onset in childhood but usually begins in adolescence or young adulthood; in more than 80 percent of patients, the onset is before 30 years of age, and the physician should be cautious in attributing headaches that appear for the first time after this age to migraine, although there are many exceptions.
In younger women, the headaches may occur during the premenstrual period; in approximately 15 percent of such migraineurs, the attacks are exclusively perimenstrual Menstrual migraine (also termed catamenial migraine) discussed further on, had been considered to be solely related to the withdrawal of estradiol (based on the work of Somerville). It is now acknowledged that the influence of sex hormones on headache is more complex. Migraine tends to cease during the second and third trimesters of pregnancy in 75 to 80 percent of women, and in others they continue at a reduced frequency; less often, attacks of migraine or the associated neurologic symptoms first appear during pregnancy, usually in the first trimester.
Although migraine commonly diminishes in severity and frequency with age, it may actually worsen in some postmenopausal women, and estrogen therapy may either increase or, paradoxically, diminish the incidence of headaches. The use of birth control pills is associated with an increased frequency and severity of migraine and in rare instances has resulted in a permanent neurologic deficit (see further on and Chap. 33).
Some patients link their attacks to certain dietary items—particularly chocolate, cheese, fatty foods, oranges, tomatoes, and onions—but these connections have proved invalid in most carefully done studies and, except in the occasional persuasive individual instance. Some of these foods are rich in tyramine, which has been incriminated as a provocative factor in migraine. Alcohol, particularly red wine or port, regularly provokes an attack in some persons; in others, headaches are fairly consistently induced by exposure to glare or other strong sensory stimuli, sudden jarring of the head (“footballer’s migraine”), or by rapid changes in barometric pressure. A common trigger is excess caffeine intake or withdrawal of caffeine.
Migraine with aura may occur at any time of day, in some individuals, arising frequently after awakening. During the preceding day or so, there may have been mild changes in mood (sometimes a surge of energy or a feeling of well-being), hunger or anorexia, drowsiness, or frequent yawning. Then, abruptly, there is a disturbance of vision consisting usually of unformed flashes of white, or silver, or, rarely, of multicolored lights (photopsia). This may be followed by an enlarging blind spot with a shimmering edge (scintillating scotoma), or formations of dazzling zigzag lines (arranged like the battlements of a castle, hence the term fortification spectra, or teichopsia). Lashley’s description and drawings of his own auras over 10 min are instructive (Fig. 9-1). The expansion and movement across the visual field of the scotoma and the fortification, maintaining a consistent but expanding shape, are notable.
Drawings by K.S. Lashley of his own expanding scotoma with fortification spectra at the edges. “X” indicates point of fixation. The visual aberration expands over minutes (indicated by numbers) and slowly moves peripherally. (Reproduced with permission from Lashley KS: Archives of Neurology 46:331, 1941.)
Other patients complain instead of blurred or shimmering or cloudy vision, as though they were looking through thick or smoked glass or the wavy distortions produced by heat rising from asphalt. These luminous hallucinations move slowly across the visual field for several minutes and may leave an island of visual loss in their wake (scotoma); the latter is usually homonymous (involving corresponding parts of the field of vision of each eye), pointing to its origin in the visual cortex. Patients often attribute these visual symptoms to one eye rather than to parts of both fields. Ophthalmologic abnormalities of retinal and optic nerve vessels have been described in some cases but are not typical.
Other neurologic symptoms, less common than visual ones, include numbness and tingling of the lips, face, and hand (on one or both sides); slight confusion of thinking; weakness of an arm or leg; mild aphasia or dysarthria, dizziness, and uncertainty of gait or drowsiness. Only one or a few neurologic phenomena are present in any given patient and they tend to occur in more or less the same combination in each attack. If weakness or paresthetic numbness spreads from one part of the body to another, or if one neurologic symptom follows another, this occurs relatively slowly over a period of minutes (not over seconds, as in a seizure, or virtually simultaneously in all affected parts as in a transient ischemic attack).
The visual or neurologic symptoms usually last for less than 30 min, sometimes longer. As they recede, a unilateral dull pain develops of slowly increasing intensity that progresses to a throbbing headache (usually but not always on the side of the cerebral disturbance). At the peak of the pain, within minutes to an hour, the patient may be forced to lie down and to shun light (photophobia) and noise (phonophobia). Light is irritating and may be painful to the globes, or it is perceived as overly bright (dazzle) and strong odors are disagreeable. Nausea and, less often, vomiting may occur. The headache lasts for hours and sometimes for a day or even longer and is often the most disabling feature of the illness. The temporal scalp vessels may be tender and the headache is worsened by strain or jarring of the body or head. Pressure on the scalp vessels or carotid artery may momentarily reduce the pain and releasing pressure accentuates it.
Between attacks, the migrainous patient is normal. In the past, it was believed that a migrainous personality existed, characterized by tenseness, rigidity of attitudes and thinking, meticulousness, and perfectionism. Further analyses, however, have not established a particular personality type in the migraineur. A relationship of migraine to epilepsy in general is also tenuous; however, the incidence of seizures is slightly higher in migrainous patients and their relatives than in the general population, and there are syndromes that encompass both disorders. In surveys, affective disorders, particularly depressive and anxiety disorders, are more common in patients with migraine than would be expected by chance.
Some patients note that their attacks of migraine tend to occur during the “let-down period,” after many days of hard work or tension. There is an overrepresentation of motion sickness or a vague instability of vision or accommodation, sensitivity to striped patterns, fainting, and of fleeting sensory symptoms on one side of the body in migraineurs. Moreover, as appreciated by Graham, migraine has a lifetime profile and is a familial disease that includes some or many of the following: colic in infancy, motion sickness, episodic abdominal pain, fainting, alcohol sensitivity, exercise-induced headaches, “sinus headaches,” “tension headaches,” and menstrual headaches. These are fairly dependable markers of the disease, and their absence in the patient or family members should at least cause the consideration of alternative explanations for cranial pain.
Alternative Patterns of Migraine
Much variation occurs in migraine. As already alluded to, the headaches need not be unilateral and the pulsatile aspect may not be prominent. The headache may be exceptionally severe and abrupt in onset (“crash migraine” or “thunderclap headache”), raising the specter of subarachnoid hemorrhage. Careful questioning in these cases sometimes reveals that the headache did not truly attain its peak rapidly but evolved over several minutes. Nonetheless, the distinction of this type of “thunderclap headache” from subarachnoid hemorrhage can be made only by examination of the CSF and imaging of the brain (see further on).
A headache may at times precede or accompany, rather than follow, the neurologic abnormalities of migraine with aura. Although typically hemicranial (the French word migraine is said to be derived from megrim, which, in turn, is from the Latin hemicrania, and its corrupted forms hemigranea and migranea), the pain may be frontal, temporal, or, quite often, generalized. Furthermore, throbbing or pulsating pain is not an inviolate feature.
Any two of the three principal components—neurologic abnormality, headache, and gastrointestinal upset—may be absent. With advancing age, for example, in some instances there is a tendency for the headache and nausea to become less severe, finally leaving only the neurologic abnormality, which itself recurs with decreasing frequency. This is also subject to great variation. One common configuration is a full-blown visual aura without subsequent headache (migraine without headache, or migraine dissocié). Visual and neurologic disturbances differ in detail from patient to patient; numbness and tingling of the lips and the fingers of one hand are probably next in frequency after visual displays, followed by transient dysphasia or thickness of speech and hemiparesis as mentioned earlier. Rarely, there is sudden, transient blindness or hemianopia at the onset of a migraine attack, accompanied by only mild headache.
Furthermore, there are several special forms of migraine that do not conform to the usual patterns discussed above, as listed in the following section.
Migraine Variants and Migraine under Special Circumstances
In addition to variability in the pattern of conventional migraine detailed just above, there are several distinctive syndromes that have been allied with migraine. They are so classified because they have as main features recurrent migrainous headache with reversible neurological deficits or visual displays that are identifiable as aura components of typical migraine. What sets them apart from conventional migraine is paralysis, stupor, ophthalmoplegia, or monocular visual loss. Furthermore, patients or their families may display both typical migraine and one of these variants.
Migraine with Brainstem Aura (Basilar Migraine)
An uncommon form of the migraine syndrome with prominent premonitory brainstem symptoms was described by Bickerstaff. These patients, usually children with a family history of migraine, first develop visual phenomena like those of typical migraine except that they occupy much or the whole of both visual fields (temporary cortical blindness may occur). There may be associated vertigo, staggering, incoordination of the limbs, dysarthria, and tingling in both hands and feet, and sometimes around both sides of the mouth but curiously, rarely is there paralysis. These symptoms last 10 to 30 min and are followed by headache, which is usually occipital. Some patients, at the stage when the headache would have been likely to begin, may faint, and others become confused or stuporous, a state that may persist for several hours or longer. Exceptionally, there is an alarming period of coma or quadriplegia. The symptoms closely resemble those caused by ischemia in the territory of the basilar-posterior cerebral arteries—hence the name basilar, or vertebrobasilar migraine. Subsequent studies have indicated that basilar migraine, although more common in children and adolescents, affects men and women more or less equally over a wide age range, and that the condition is not always benign and transient because of rare instances with residual deficits.
The initial attack is not easily identifiable as a benign condition and various forms of imaging are reasonably performed in order to exclude basilar artery and upper brainstem disease. The issue of risk of causing stroke from the administration of intrarterial contrast is often raised and is unresolved. With recurrent similar attacks, the diagnosis becomes clearer and the use of imaging becomes less necessary.
Childhood Periodic Syndrome
Episodes of cyclic vomiting or periodic recurrent abdominal pain have been linked to migraine as a result of the frequent co-occurrence of these symptoms with headache or typical migraine at other times. Pallor, lethargy, and mild headache are common. This episodic disorder seems to be a problem almost exclusively of children. The results of diagnostic investigation are normal but one cannot be faulted for pursuing some form of testing with the initial occurrence of the syndrome.
Dizziness is certainly a common accompaniment of migraine and its auras. A less certain syndrome associates episodic vertigo with migraine, mainly in children but also in some adults who are known migraineurs. Patients report varying degrees and types of dizziness, are disturbed by highly patterned or crowded visual environments, and can be disabled by imbalance but the examination during a symptomatic period is most often normal. Many of these features accord with anxiety but the episodic occurrence of symptoms and interspersed attacks of migraine make the connection plausible. Bedside vestibular testing is normal, however, a proportion of patients is found to have minor central or peripheral deficits on more elaborate laboratory testing (see Chap. 14). Similarly, a tenuous relationship between an episodic vertigo syndrome and migraine in children, as described by Basser, is discussed in Chap. 14.
Ophthalmoplegic migraine in the current terminology of the International Headache Society is “recurrent painful ophthalmoplegic neuropathy” rather than migraine but it is most conveniently described here. It consists of a recurrent unilateral headaches associated with weakness of extraocular muscles. A transient third-nerve palsy with ptosis, with or without involvement of the pupil, is the usual picture; rarely, the sixth nerve is affected. This disorder almost exclusively occurs in children. As a general rule, the diagnosis should not be made in adults unless there had been recurrent bouts in childhood. The ocular paresis often outlasts the headache by days or weeks; after many attacks, a slight mydriasis and some degree of ophthalmoparesis may remain permanently. We and others have encountered instances of gadolinium enhancement of the proximal, cisternal portion of the third nerve during and after an attack. However, in adults the syndrome of headache, unilateral ophthalmoparesis, and loss of vision may have more serious causes, including temporal (cranial) arteritis.
In another entity that is more clearly allied with migraine than the ophthalmoplegic variety above, retinal, or ocular migraine, there are purely monocular visual symptoms of scintillations or scotoma (in contrast to the often reported unilateral but actually asymmetric homonymous nature of these symptoms). The visual loss can be quite severe or complete but is transient and recovers fully. Often in our experience, there is no headache but if one is present, it is of the typical migraine type, not ocular pain. In some cases of uniocular visual disturbance with scotoma, fortuitous examination during an attack may reveal attenuation of the retinal arterioles as noted by Berger and colleagues. Most often, there are no funduscopic changes. Either the retinal or the ciliary circulation is probably involved. Knowledge of this syndrome in a young healthy person may prevent excessive evaluation and unnecessary treatment, although antiphospholipid antibody syndrome and other hypercoagulable states are considerations. In older persons, carotid disease and giant cell arteritis merit investigation.
Hemiplegic Migraine (Familial Hemiplegic Migraine)
In the disorder hemiplegic migraine, a condition mostly of infants and children (rarely adults), there are episodes of unilateral paralysis that may long outlast the headache. Other unusual clinical features have been unilateral massive brain swelling with recovery, putatively in some cases triggered by minor head injury.
Families have been described in which this condition is the result of a mutation in an ion channel (familial hemiplegic migraine; alternating hemiplegia of childhood). Of the known loci, which together account for more than half of cases, the most common one is in the gene coding for the P/Q-type calcium channel α subunit (CACNA1A). A second locus is in the gene for the Na+/K+-adenosine triphosphatase (ATPase) channel (ATP1A2) and a rarer subtype is caused by mutations in a sodium channel α-subunit gene (SCNA1). These, however, do not account for all cases, indicating that other mutations will inevitably be discovered. It is reasonable to surmise that many of the nonfamilial cases of hemiplegic migraine are also caused by these mutations.
By their nature, these channelopathies would be expected to have clinical and genetic overlap with other neurologic diseases. Indeed, there are shared traits between some of the genetic forms of familial hemiplegic migraine and both episodic and degenerative cerebellar diseases (Goadsby, 2007). Ducros and colleagues have found a variety of other neurologic features in these families, including persistent cerebellar ataxia and nystagmus in 20 percent; others had attacks of coma and hemiplegia from which they recovered. Also notable because of genetic overlap are an acetazolamide-responsive ataxia that has in common other mutations in the CACNA1A gene, and the cerebrovascular disorder known as CADASIL, discussed in Chap. 33, which, in rare families, presents with hemiplegic migraine but instead is related to the Notch3 gene on the same chromosome (19).
Complicating the situation is the undoubted existence of sporadic migraine with transient hemiplegia that has no familial trait (see further on under Transient Ischemic Attacks and Stroke with Migraine). Neurologic symptoms lasting more than an hour or so should prompt investigation for alternative causes, but none may be found. Instances of hemiplegic migraine may account for some of the inexplicable strokes in young women and older adults of both sexes, as also discussed further on. The treatment of these conditions is discussed in a later section.
In some individuals, migraine attacks, for unaccountable reasons, may increase in frequency for several months. As many as three or four attacks may occur each week, leaving the scalp on one side continuously tender. When this occurs for more than half of the days in a month, the International Headache Society terms the condition chronic migraine.
An even more difficult clinical problem is posed by migraine that lapses into a debilitating condition of severe continuous headache (status migrainosus; defined by the Headache Society as lasting greater than 72 h). The pain is initially unilateral, later more generalized, more or less throbbing, but with a constant superimposed ache and is disabling; vomiting or nausea is common at the outset but abates. The absence of prior headaches should raise concern about a more serious cause. Status migrainosus sometimes follows a head injury or a viral infection, but most cases have no explanation.
Relief is often sought by increasing the intake of ergot or serotonin agonist preparations or even opioids, often to an alarming degree, but with only temporary relief, serving at times to perpetuate the condition. In the diagnosis of such persistent cases, the possibility should be considered that migraine has been complicated by this type of overuse of symptomatic medications with subsequent (“rebound”) worsening of headache. This cycle may produce a transformation of previously intermittent migraine into a low grade continuous headache with superimposed migrainous exacerbations. Narcotic addiction is another worry. In cases of status migrainosus, it is our practice to discontinue narcotic medications, and administer several of the following: intravenous hydration, metoclopramide, rapidly acting nonsteroidal anti-inflammatory drugs, magnesium, corticosteroids, or dihydroergotamine intravenous infusion in selected patients (see further on for details of treatment). In all likelihood, the patient has already been treated unsuccessfully with several medications and furthermore, the widely used serotonin agonist (“triptan”) medications are less likely to be helpful at this later stage of migraine.
Migraine-Like Headaches With CSF Pleocytosis
An intriguing problem arises in the patient with migraine who is found to have a slight lymphocytic pleocytosis in the spinal fluid. Most of these cases in our experience have proved to be simply instances of aseptic meningitis that have precipitated migraine in susceptible individuals. In others, a few cells are found in the spinal fluid during an attack of migraine without obvious explanation; probably a minor cellular reaction of 3 to 10 white blood cells (WBCs)/mL may be innocuous if there is no fever or meningismus.
A more extensive syndrome was described by Bartleson, Swanson, and Whisnant under the title “A migrainous syndrome with cerebrospinal fluid pleocytosis.” A subsequent series by Berg and Williams introduced the acronym HaNDL (headache with neurological deficits and CSF lymphocytosis). The most extensive report was by Gomez-Aranda and colleagues, who described 50 adolescents and young adults, predominantly males, who developed multiple widely separated episodes of transient neurologic deficits lasting hours, accompanied by migraine-like headaches, sometimes with slight fever but no stiff neck. One-quarter of this group had a history of past migraine and a similar number had a viral-like illness within 3 weeks of the neurologic problem. The CSF contained from 10 to 760 lymphocytes per cubic millimeter, and the total protein was elevated. The transient neurologic deficits were mainly sensorimotor, often involving the hand and lips, and aphasia; only 6 patients had visual symptoms. The patients were asymptomatic between attacks and in none did the entire illness persist beyond 7 weeks. We have observed several cases, all in otherwise healthy middle-aged men and we found corticosteroids to be helpful.
It is important to exclude an immune reaction to nonsteroidal anti-inflammatory medications or to intravenous immunoglobulin, which are among the agents that cause otherwise unexplained aseptic meningitis and headache but generally not with migraine features.
The causation and pathophysiology of the HaNDL syndrome and its relation to migraine are obscure but may relate to a hypothesized neurogenic inflammation basis of migraine discussed further on. The distinction between this syndrome and the recurrent aseptic meningitis of Mollaret and other chronic meningitic syndromes as well as cerebral vasospasm or vasculitis is difficult (see “Chronic Persistent and Recurrent Meningitis” in Chap. 31).
Migraine Following Head Injury
In addition to acute and chronic forms of generalized post-traumatic headache, cranial trauma of almost any degree may precipitate a migraine in persons prone to the condition. A particularly troublesome variant occurs in a child or adolescent who, after a trivial or mild head injury, may lose vision, suffer severe headache or be plunged into a state of confusion, with belligerent and irrational behavior that lasts for hours or several days before clearing. The possible relationship to familial hemiplegic migraine and channelopathy has been mentioned earlier. In yet another variant, there is an abrupt onset of either one-sided paralysis or aphasia after virtually every minor head injury (we have seen this condition several times in college athletes) but without visual symptoms and little or no headache. Although a family history of migraine is frequent in such cases, there has been no history of hemiplegia in other family members. Of course, more treacherous conditions such as carotid artery dissection and subdural hematoma can simulate post-traumatic migraine.
Migraine in Young Children
This may present special difficulties in diagnosis, as a young child’s capacity for accurate description is limited. Instead of complaining of headache, the child appears limp and pale and complains of abdominal pain; vomiting is more frequent than in the adult, and there may be slight fever. Recurrent attacks were referred to in the past by pediatricians as the “periodic syndrome” as discussed in an earlier section. Another variant in the child is episodic vertigo and staggering (paroxysmal disequilibrium) followed by headache, probably a type of basilar migraine (see Watson and Steele). Also, there are puzzling patients with bouts of fever or transient disturbances in mood (“psychic equivalents”) and abdominal pain (abdominal migraine), that had been attributed to migraine.
Infants and young children may have attacks of hemiplegia (without headache), first on one side then the other, every few weeks. Recovery is usually complete, and arteriography in one child, after more than 70 attacks, was normal. Alternating hemiplegia of childhood may terminate in a dystonic state. There is probably a relationship of this condition to familial hemiplegic migraine (see earlier). One advantage of considering such attacks as migrainous is that it may protect some patients from repeated diagnostic procedures and surgical intervention; but, by the same token, it may delay appropriate investigation and treatment.
There are many causes of headache during pregnancy, as discussed further on, but among the most frequent and important is migraine. During pregnancy, migraines tend to abate, although there are notable exceptions, especially in the third trimester. It is not unusual to hear reports of auras dissociated from headache during pregnancy but, a marked change of headache pattern during pregnancy should lead to consideration of alternative diagnoses such as toxemia or cerebral venous sinus thrombosis. Nevertheless, migraine may make its first appearance during pregnancy, particularly in the first trimester. The causes of headache in a single-center study of pregnant women are given by Robbins and colleagues as detailed further on, who emphasize that migraine remains the most common, followed by a number of hypertensive disorders.
The treatment of migraine during pregnancy presents special issues that are discussed further on.
Transient Ischemic Attacks and Stroke With Migraine
Migraine complicated by stroke
Rarely, migrainous neurologic symptoms, instead of being transitory, leave a prolonged or even permanent deficit (e.g., homonymous hemianopia), indicative of an ischemic stroke (See Also Chap. 33.). A small number of these are attributed to migrainous infarction rather than being attributable to conventional mechanisms of stroke. Platelet aggregation, edema of the arterial wall, increased coagulability, dehydration from vomiting, and intense, prolonged spasms of vessels have all been implicated (on rather uncertain grounds) in the pathogenesis of arterial occlusion and strokes that complicate migraine (Rascol et al).
Furthermore, attacks of migraine, particularly with prominent neurologic symptoms, instead of beginning in childhood, may have their onset later in life, and Fisher provided support for the hypothesis that some of the transient aphasic, hemianesthetic, or hemiplegic attacks of later life may be of migrainous origin (“late life migraine accompaniments”). With careful questioning, many of these patients with TIA syndromes will recall a history of migraine headaches in youth.
The reported incidence of stroke complicating migraine has varied. At the Mayo Clinic, in a group of 4,874 patients, ages 50 years or younger with a diagnosis of migraine, migraine equivalent, or vascular headache, 20 patients had migraine-associated infarctions (Broderick and Swanson). Caplan described 7 patients in whom attacks of migraine were complicated by strokes in the vertebrobasilar territory. A study by Wolf and colleagues collected 17 instances of stroke and migraine. Most had a prolonged aura, either visual, sensory, or aphasic and over two-thirds of the strokes, demonstrated by diffusion restriction on MRI, were in the posterior circulation territory and occurred in younger women. There is, nonetheless, a paucity of useful pathology by which to interpret the mechanism of migraine-associated stroke. The uncertain but potential role of antimigraine medications in producing stroke is discussed further on in the section on treatment. Estrogen medications have also been implicated in stroke in some women migraineurs. The complex relationship between acute stroke and the use of triptans or ergots for the treatment of migraine is addressed in a later section.
In children and young adults with the mitochondrial disease MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and in adults with the rare cerebral vasculopathy CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), migraine may be a prominent feature. Chapter 33 addresses these issues further.
The special problem of focal cerebral disorders associated with segmental or diffuse vasospasm, including the form that follows treatment with the “triptan” (serotonin agonist) drugs and Call-Fleming syndrome, is discussed further on in the section on treatment and under “Diffuse and Focal Cerebral Vasospasm” in Chap. 33.
Epidemiologic association between migraine and stroke
A separate set of observations, mainly epidemiologic, pertain to the risk of strokes, particularly in women with migraine. Despite some variability in conclusions between studies, meta-analyses have suggested that there is a two-fold increase of lifetime incidence of ischemic stroke in individuals with migraine and aura (see, e.g., Spector et al). The risk may increase with increasing migraine attack frequency and particularly with oral contraceptive use and smoking, which together may confer a ninefold increase in risk. For example, in the Northern Manhattan Study by Monteith and colleagues, migraine was associated with future stroke but only in smokers. There may be a similar increase in cardiovascular events later in life but the evidence for this is uncertain and difficult to disengage from confounding risk factors. A meta-analysis of case control and cohort studies conducted by Schüks and colleagues were unable to demonstrate an increased risk for cardiovascular events. Other investigators, again depending on various population databases and few patient level studies, have come to the opposite conclusion (Bigal et al) and suggested that all cause mortality is increased in migraine patients (Gudmundsson et al). There are also emerging but tentative connections between genetic variants and shared risks for stroke and migraine.
The issue of oral contraceptives as a risk for stroke in migraineurs is a more complicated matter that has not been entirely resolved except that the risk may be greater in women who have migraine with aura. The pills are not entirely interdicted in migraineurs but several guidelines suggest against the use of oral contraceptives if there is migraine with aura. Perhaps lower estrogen compounds are advisable in migraine without aura as formulations with high estrogen concentrations have been associated with clotting in the venous circulation.
Finally, there has long been discussion of an association between migraine and patent foramen ovale. A few physicians in the past favored a causal role and advocated closure of the foramen in an attempt to alleviate migraine but several trials have failed to sustain this concept. Migraine with aura has been especially associated with an open foramen. However, large cross-sectional (Rundek et al) and case-control (Garg et al) studies have not affirmed these associations and the issue, while still under discussion, has been of waning interest.
Imaging changes in migraine
There are cerebral imaging changes in migraineurs that are suggestive of small ischemic lesions. A number of cross-sectional population studies, such as the ones by Kurth and colleagues, Scher et al, and Kruit and coworkers, have indicated that MRI changes in both the deep and subcortical white matter are more frequent in women migraine patients who experienced auras than in those without auras and in the general population. A high frequency of migraine headaches is also associated in some studies with an increased number of white matter lesions including, according to some observers, lesions in the cerebellar white matter.
The implications of these frequently encountered small white matter lesions in migraineurs that are familiar to neurologists are unclear. The findings are a cause for neurological consultation, sometimes with the question of multiple sclerosis. Several studies indicate that migraineurs with these changes have no greater cognitive decline over time than those in the general population. In discussion with patients, we tend to underemphasize these lesions and the risk of stroke but point out that the importance of the usual stroke risk factors: smoking, hypertension, hyperlipidemia, and cardiac rhythm abnormalities.
So far, it has not been possible to determine from the many clinical observations and investigations, a unifying theory as to the cause of migraine. Tension and other emotional states, which are claimed by some migraineurs to precede their attacks, are so inconsistent as to be no more than potential aggravating factors. Clearly, an underlying genetic factor is implicated, although it is expressed in a recognizable mendelian pattern in only a small number of families (see above). How this genetic predisposition is translated periodically into a regional neurologic deficit, unilateral headache, or both is unknown. For many years, our thinking about the pathogenesis of migraine was dominated by the views of Harold Wolff and others—that the headache was caused by the distention and excessive pulsation of branches of the external carotid artery. Certainly, the throbbing, pulsating quality of the headache and its relief by compression of the common carotid artery supported this view, as did the early observation of Graham and Wolff that the headache and amplitude of pulsation of the extracranial arteries diminished after the intravenous administration of ergotamine.
The importance of vascular factors continues to be emphasized by more recent findings, but not in the way envisaged by Wolff. For example, in a group of 11 patients with classic migraine, Olsen and colleagues, using the xenon inhalation method, noted a regional reduction in cerebral circulation spreading forward from the occipital region during the period when neurologic symptoms appear. They concluded that the reduction in blood flow was consistent with the cortical spreading depression syndrome described below. In a subsequent study, Woods and colleagues described a patient who, during positron emission tomography (PET), fortuitously had an attack of common migraine with blurred vision. Sophisticated measurements showed a reduction in blood flow that started in the occipital cortex and spread slowly forward on both sides, in a manner much like spreading cortical depression (see below) and Cutrer and colleagues, using perfusion-weighted MRI, corroborated the finding of diminished occipital cerebral blood flow during the aura. However, a study using single-photon emission computed tomography (SPECT) in 20 patients during and after attacks of migraine without aura disclosed no focal changes of cerebral blood flow; also, no changes occurred after treatment of the attacks with 6 mg of subcutaneous sumatriptan (Ferrari et al, 1995).
In reference to the extracranial vessels, Iversen and associates, by means of ultrasonography, documented a dilatation of the superior temporal artery on the side of the migraine during the headache period. The same dilatation in the middle cerebral arteries has been inferred from observations with transcranial Doppler insonation. The complication of cerebral infarction is also in keeping with a vascular hypothesis, but it involves only a tiny proportion of migraineurs. The vascular hypothesis for migraine must be regarded as uncertain, but, clearly, there is frequently a reduction in posterior cortical blood flow during an aura. What is not established is whether the blood flow changes are fundamental or simply the result in a reduction in cortical activity. The original opinion expressed by Wolff that a vascular element is responsible for the cranial pain of migraine is also unconfirmed.
The relationship between the vascular changes and evolving neurologic symptoms of migraine are noteworthy. Lashley, who as noted earlier (see Fig. 9-1) plotted his own visual aura, calculated that the cortical impairment progressed at a rate of 2 to 3 mm/min over the surface of the brain. The site of activity putatively begins in one occipital lobe and extends forward slowly (2.2 mm/min) as a wave of “spreading oligemia” that does not respect arterial boundaries (Lauritzen and Olesen). Both of these events are intriguingly similar to the above-mentioned phenomenon of “spreading cortical depression,” observed by Leão in experimental animals. He demonstrated that a noxious stimulus applied to the rat cortex was followed by vasoconstriction and slowly spreading waves of inhibition of the electrical activity of cortical neurons, moving at a rate of approximately 3 mm/min. Lauritzen and Olesen attribute both the aura and spreading oligemia to the spreading cortical depression, and considerable work since then has corroborated this idea. These observations, however, apply only to the aura.
An alternative, but not necessarily exclusive hypothesis links the aura and the painful phase of migraine through a neural mechanism originating in the trigeminal nerve as proposed by Moskowitz. This is based on the innervation of extracranial and intracranial vessels by small unmyelinated fibers of the trigeminal nerve that subserve both pain and autonomic functions (the “trigeminovascular” complex). This model provides an explanation for migraine pain as originating in the trigeminal ganglion. Activation of these fibers releases substance P, calcitonin gene-related peptide (CGRP), and other peptides into the vessel wall, which serves to sensitize the trigeminal system to the pulsatility of cranial vessels, and to increase their permeability, thereby promoting an inflammatory response. The small molecules released from nerve endings adjacent to the cortex would then incite spreading depression in this model. Against this hypothesis is the occurrence of headache as often as not on the side opposite the side of generation of the aura and the lack of clinical effect of drugs that work in this experimental model. Most likely, both neural and vascular mechanisms are operative and they interact.
In part to address the action of the serotonin agonist drugs on migraine (see below), a body of evidence has been assembled that serotonin (5-HT) acts as a humoral mediator in the neural and vascular components of migraine headache. Serotonin is discharged from platelets at the onset of headache and the headache is reduced by the injection of 5-HT. This led to the development by Humphrey of sumatriptan, which acted selectively on 5-HT1B/D receptors so as to reduce side effects. This was the forerunner of the large group of “triptans.” More recently, nitric oxide generated by endothelial cells has been implicated as the cause of the pain of migraine headache, but the reason for its release and the relationship to changes in blood flow is unclear.
Blau and Dexter and Drummond are confident that the presence or absence of headache does not depend solely on extracranial vascular factors. These authors point to their findings that occlusion of blood flow through the scalp or common carotid circulation fails to alleviate the pain of migraine in one-third to one-half the patients. Lance and Goadsby have has suggested that the trigeminal pathways are in a state of persistent hyperexcitability in the migraine patient and that they discharge periodically, perhaps in response to hypothalamic stimulus acting on the endogenous pain control pathways. This is in keeping with current theories regarding the trigeminovascular complex discussed earlier, as well as with evolving ideas on central sensitization to pain because of repeated noxious stimulation from one body region that may produce a type of centrally mediated allodynia. The role of alternative factors in migraine has been reviewed in the monograph by Lance and Goadsby.
The foregoing observations leave a number of questions unanswered. Is one to conclude that migraine with and without aura are different diseases, involving extracranial arteries in one instance and intracranial ones in another? Is the circulatory change the primary cause of headache, or is it a secondary or coincidental phenomenon? Is diminished neuronal activity (spreading depression) the primary cause of neurologic symptoms (it seems so) and headache (unclear), and is the diminished regional blood flow secondary to reduced metabolic demand? Why are the posterior portions of the brain (visual auras) so often implicated (perhaps because of richer trigeminal innervation of the posterior vessels)? The neural mechanisms that underlie these changes and precisely what is altered by the genetic predisposition to migraine are unresolved. No final reconciliation of all these data is possible and migraine remains incompletely explained.
Migraine with aura should occasion no difficulty in diagnosis if a proper history is obtained. Most often, the symptoms begin as “positive,” that is, scintillation, paresthesia, as opposed to the later “negative” scotoma, numbness, aphasia, or paresis. The difficulties come from a lack of awareness that a progressively unfolding neurologic syndrome may be migrainous in origin and may occur without headache. Furthermore, recurrent migraine headaches take many forms, some of which may prove difficult to distinguish from the other common types of headache, and it should be recognized that migraine headaches need not be severe or disabling. Some of these problems merit elaboration because of their practical importance.
The neurologic part of the migraine syndrome may resemble a transient ischemic attack, focal epilepsy, the clinical effects of a slowly evolving hemorrhage from an arteriovenous malformation, or a thrombotic or embolic stroke. It is the pace of the neurologic symptoms of migraine that distinguish it from epilepsy and most cases of stroke. Furthermore, the positive rather than ablative nature of the symptoms assists in distinguishing it from the usual stroke syndromes.
Recurrent painful ophthalmoplegic cranial neuropathy (formerly ophthalmoplegic migraine, mentioned earlier) may suggest a carotid-cavernous or supraclinoid aneurysm. Transient monocular blindness from carotid stenosis is infrequent in the age group affected most by migraine, but the antiphospholipid syndrome, which has some ill-defined relationship to migraine, does cause episodic unilateral visual loss in this group and should be sought as the explanation for transient monocular blindness with or without headache.
One accepts that the headache of migraine may be almost exclusively on one side of the head but the invariant occurrence of migraine-like headache on the same side of the head increases the likelihood of an underlying arteriovenous malformation (AVM) or other structural lesion. R.D. Adams, who studied more than 1,200 patients with AVM found that the headaches, which occurred in more than 30 percent of these individuals, usually did not include the other features of either migraine or cluster headache. However, in about 5 percent, the headaches were associated with visual aura, making them indistinguishable from migraine with aura. In most, the AVM was in the occipital region and on the side of the headache. Approximately half of the patients with AVM and migraine had a family history of migraine. It is unclear to us if AVM can be regarded as an acknowledged cause of recurrent migraine-like headache. It is, of course, possible that given the ubiquity of migraine in the population, that the association is coincidental.
This topic may be divided into two parts—control of the individual acute attack, and prevention that includes both the use of medications and of lifestyle modifications. The time to initiate treatment of an acute attack is during the neurologic (visual) prodrome or at the very onset of the headache (see below). If the headaches are mild, the patient may already have learned that aspirin, acetaminophen, or another nonsteroidal anti-inflammatory drug (NSAID) will suffice to control the pain. Insofar as a good response may be obtained from one type of NSAID and not another, it may be advisable to try two or three preparations in several successive attacks of headache and to use moderately high doses if necessary. The combination of aspirin or acetaminophen, caffeine, and butalbital, although popular with some patients, is usually incompletely effective if the headache is severe and is also capable of causing dependence. Numerous other medications have proved effective and each has had a period of popularity among neurologists and patients.
Because of the differing modes of absorption the ideal timing differs for administration of each type of preparation. The ostensible goal is attain a high concentration of the drug at the onset of headache. For severe attacks of migraine headache, sumatriptan or one of the other serotonin agonist “triptans” in this class (e.g., zolmitriptan, rizatriptan, naratriptan, almotriptan, eletriptan, and frovatriptan), or the ergot alkaloids, ergotamine tartrate, and particularly dihydroergotamine (DHE), are the effective forms of treatment and are best administered early in the attack, ideally just after a visual aura or at the onset of headache. Patients with waning visual auras should be advised to wait to self-administer subcutaneous serotonin agonists until the headache begins. Clinical experience and the study by Bates and colleagues suggests that the subcutaneous triptans are ineffective in preventing headache if given during the aura; they are however, probably safe (see below). In contrast, the slightly slower acting nasal spray or the even slower acting oral formulations are often ineffective if given too long after the start of headache. Patients have therefore learned to administer the nasal and oral preparations during the aura and the subcutaneous drugs as close to the onset of headache as possible.
A single 4- or 6-mg dose of sumatriptan or its equivalent, given subcutaneously, is an effective and well-tolerated treatment for migraine attacks (see Subcutaneous Sumatriptan Study cited in the references). When successful, it eliminates or reduces the accompanying symptoms of nausea, vomiting, photophobia, and phonophobia. An advantage of the serotonin agonist drugs, aside from their relative safety, is the ease of self-administration using prepackaged injection kits, thus avoiding frequent and inconvenient visits to the emergency department. Sumatriptan can also be given orally in a 25-, 50-, or 100-mg tablet and as a nasal spray (20 mg per spray), zolmitriptan in a 2.5- or 5-mg tablet or 5-mg nasal spray, and rizatriptan in a 5- or 10-mg dose tablet, repeated, if needed, in 2 h. For oral preparations, latency for headache relief is longer than with subcutaneous injection or inhalation. If one serotonin agonist is found to be ineffective, another drug or an alternative route of administration, such as intranasal, may be tried. These medications are summarized in Table 9-2.
Table 9-2TRIPTANS FOR ORAL USE
A large and often cited meta-analysis of the available drugs in 53 separate trials conducted by Ferrari and colleagues (2001) found modest differences in overall efficacy between drugs. Loder has given a tabulated comparison of the main drugs for migraine and a review of their use in routine situations.
Ergotamine is an equally effective agent, but its peripheral and coronary vasoconstricting side effects, including nausea, have reduced its use. This is an alpha-adrenergic agonist with strong serotonin receptor affinity and vasoconstrictive action. The drug is taken as an uncoated 1- to 2-mg tablet of ergotamine tartrate, held under the tongue until dissolved (or swallowed), or in combination with caffeine. Repeat use is not advisable as it may lead to prolonged or daily headache. A single oral dose of promethazine 50 mg, or of metoclopramide 20 mg, given with the ergotamine, allays the potential nausea and vomiting from ergotamine and may have independent effects on reducing the severity of headache. Patients in whom vomiting prevents oral administration may be given ergotamine by rectal suppository or DHE by nasal spray or inhaler (one puff at onset and another at 30 min) or can learn to give themselves a subcutaneous injection of DHE (usual dosage, 1 mg). Caffeine, 100 mg, is thought, on slim evidence, to potentiate the effects of ergotamine and other medications for migraine. When ergotamine is administered early in the attack, the headache will be abolished or reduced in severity and duration in 70 to 75 percent of patients.
An important problem pertains to the risk of stroke from serotonin agonists in patients with prolonged visual aura or other focal neurologic symptoms associated with the headache. What evidence exists suggests the risk of stroke is low or nonexistent as, for example, in the epidemiologic study by Hall and colleagues. As a matter of course, however, serotonin agonists and ergots are generally avoided if there is an ongoing and prolonged aura of any type, including visual, but particularly with hemiparesis, aphasia, or features such as vertigo, drowsiness, or diplopia, referable to the basilar artery. Not all experts agree with this proscription and some small series, among them 13 patients reported by Klapper and colleagues, have found triptans safe to use if a headache with neurologic signs has commenced, but this issue has not been resolved. As previously noted, although this class of drugs may not be helpful during the visual aura, they also seem to do no harm (see Bates et al).
Rare cases of severe but reversible cerebral vasospasm have been reported after the use of ergotamine or a serotonin agonist drug, but most of these patients in fact had not had neurologic features as part of their initial headache syndrome. Of particular danger, however, is the often unnoticed, concurrent use of other sympathomimetic drugs such as phenylpropanolamine as in one of the cases described by Singhal and colleagues and by Meschia and associates (see discussion of Call-Fleming syndrome, “Diffuse Vasoconstriction,” “Diffuse and Focal Cerebral Vasospasm” in Chap. 33). Cerebral hemorrhage is another rare complication of serotonin agonist use that possibly relates to hypertension induced by triptans or ergots. Ergot drugs and triptans are contraindicated in symptomatic and asymptomatic coronary artery disease and poorly controlled hypertension.
For severely ill patients who arrive in the emergency department or physician’s office, having failed to obtain relief from a prolonged headache with the above medications, Raskin (1986) has found metoclopramide 10 mg IV, followed by DHE 0.5 to 1 mg IV every 8 h for 2 days, to be effective. We also use this approach as well as intravenous magnesium infusions, starting with 1 g, in cases of status migrainosus. The administration of intravenous DHE can be combined with a lidocaine infusion, this combination having not been exposed to a rigorous clinical trial. The potential success of metoclopramide alone should not be dismissed, as we and others have occasionally found that the headache abates after this initial injection. A wide array of other drugs including almost all of the conventional nonsteroidal anti-inflammatory medications has been recommended as adjunctive therapy, for example, prochlorperazine, ketorolac, and intranasal lidocaine. Each of these drugs, given alone, is effective in alleviating the headache in about half of patients, emphasizing the need for blinded placebo-controlled trials for any drug that is introduced for the treatment of headache.
Intravenous and oral corticosteroids have been found anecdotally to be useful in refractory cases and as a means of terminating migraine status. In a randomized trial of intravenous dexamethasone 10 mg in an emergency department setting, Friedman et al found no benefit. As an alternative to steroids and more commonly used nonsteroidal agents, Weatherall and colleagues used intravenous aspirin (lysine acetylsalicylate, 1 g, repeated up to five times) with reasonably good effect in inpatient management of migraine and other headache disorders. We have determined that this agent is difficult to obtain from our hospital pharmacies.
If, in an individual attack, all of the foregoing measures fail, it may be reasonable to resort briefly to narcotics, which usually give the patient a restful, pain-free sleep. Halfway measures at this point are usually futile. However, the use of narcotics as the mainstay of acute or prophylactic therapy is to be avoided. As mentioned above, if the pain does not abate in 12 to 24 h, corticosteroids in any of several regimens may be added and continued for several days.
Based on the action of certain peptides in the trigeminovascular complex, novel antagonists of CGRP have been investigated, and while symptomatically equivalent to triptans (Olesen and colleagues and also Ho et al), they have been largely abandoned because of liver toxicity with frequent use. Drugs of this type as well as inducible nitric oxide synthase (iNOS) inhibitors and receptor blockers that work by a different mechanism than do the serotonin agonists may be alternatives in the future.
In individuals with frequent migrainous attacks, efforts at prevention are worthwhile. The survey by Lipton and colleagues, found approximately one-fourth of patients were appropriate for some form of prophylactic treatment on the basis of the frequency and severity of their headaches, usually more than one severe episode per week. The most effective agents have been beta-adrenergic blockers, certain antiepileptic drugs, and tricyclic antidepressants. Often, comorbidities such as depression, hypertension, epilepsy, or coronary artery disease guide the choice among these three classes of drugs. Some headache specialists have expressed the opinion that amitryptiline may be more effective if headaches are very frequent and that propranolol is more effective if severity of headaches is the concern. Ziegler and colleagues found propranolol and amityrptiline to be equally effective as preventive measures.
Some success has been obtained with propranolol, beginning with 10 to 20 mg two to three times daily and increasing the dosage gradually to as much as 240 mg daily, probably best given as a long-acting preparation in the higher dosage ranges. Under-dosing is a major reason for ineffectiveness. If propranolol is unsuccessful or not tolerated, one of the other beta-blockers, specifically those that lack agonist properties—atenolol (40 to 160 mg/d), timolol (20 to 40 mg/d), or metoprolol (100 to 200 mg/d)—may be effective. Many practitioners have found that particularly young patients do not tolerate the fatigue and other side effects of these medications.
Alternatives, depending upon other comorbidities, are an antiepileptic medication, or our preference, a tricyclic antidepressant. Valproic acid 250 mg taken three to four times daily, other antiepileptic drug such as topiramate, or amitriptyline, 25 to 125 mg nightly may be tried. The newer antidepressants (e.g., specific serotonin reuptake inhibitors) are not as effective and may even cause headache in our experience. If these three main approaches are unsuccessful, calcium channel blockers (e.g., verapamil, 320 to 480 mg/d; nifedipine, 90 to 360 mg/d) are also reportedly effective in decreasing the frequency and severity of migraine attacks in some patients, but there is typically a lag of several weeks before benefit is attained and our success with them has been limited. Indomethacin, 150 to 200 mg/d; and cyproheptadine, 4 to 16 mg/nightly are found to be helpful in some patients and may be particularly useful in preventing predictable attacks of perimenstrual migraine.
A typical experience is for one of these medications to reduce the number and severity of headaches for several months and then to become less effective, whereupon an increase in the dosage, if tolerated, may help; or one of the many alternatives can be tried. The newest putative treatment for chronic or frequently repeating headaches, both migraine and tension, is the injection of botulinum toxin (Botox) into sensitive temporalis and other cranial muscles. Elimination of headaches for 2 to 4 months has been reported—a claim that justifies further study. Similarly, injection blockade of one or both greater occipital nerves or upper cervical roots has reportedly been helpful. Surgical decompression of sensory nerves in the scalp and related techniques have also been advocated but without documentation.
Methysergide, an ergot derivative that was more widely used in the past, in doses of 2 to 6 mg daily for several weeks or months had been effective in the prevention of migraine. Retroperitoneal and pulmonary fibroses are rare but serious complications so that the drug is no longer easily available in the United States or Canada. Some clinicians have used oral methergine as a surrogate but apparently with disappointing results according to our colleagues.
Some patients allege that certain items of food induce attacks (chocolate, peanuts, hot dogs, smoked meats, oranges, and red wine are the ones most commonly mentioned), and it is obvious enough that they should avoid these foods if possible. Limiting caffeinated beverages may be helpful. In certain cases, the correction of a refractive error, an elimination diet, or behavioral modification is said to have reduced the frequency and severity of migraine and of tension headaches. However, the methods of study and the results have been so poorly controlled that it is difficult to evaluate them. All experienced physicians appreciate the importance of helping patients rearrange their schedules with a view to controlling tensions and hard-driving lifestyles. There is no single program to accomplish this. Psychotherapy has not been helpful, or at least one can say that there is no evidence of its value. The claims for sustained improvement of migraine with chiropractic manipulation are similarly unsubstantiated and do not accord with our experience. Meditation, acupuncture, and especially biofeedback, which has shown benefit in reasonably conducted trials, all have their advocates, but again, the results, while not to be entirely discounted, are uninterpretable.
This is a group of relatively uncommon syndromes that may be allied with migraine but respond very well and specifically to indomethacin both acutely and as prophylaxis, so much so that some authors have defined a category of indomethacin-responsive headaches. These include orgasmic migraine, chronic paroxysmal hemicrania (see further on), hemicrania continua, exertional headache, hypnic headache, brief head pains (jabs and jolts and “ice-pick” headaches), and some instances of premenstrual migraine, (which respond to many nonsteroidal anti-inflammatory agents). These are summarized in Table 9-3 and discussed further on.
Table 9-3INDOMETHACIN RESPONSIVE HEADACHES ||Download (.pdf) Table 9-3INDOMETHACIN RESPONSIVE HEADACHES
Valsalva related headaches
Primary headache associated with sexual activity*
Primary exertional (exercise induced, weight lifters) headache*
Primary cough headache
Chronic paroxysmal hemicrania
Episodic paroxysmal hemicrania
“Jabs and jolts”
Idiopathic stabbing (ice pick) headache
This type of headache has been described in the past under a variety of names, including paroxysmal nocturnal cephalalgia, migrainous neuralgia, histamine cephalalgia (Horton’s headache), and others. Kunkle and colleagues, who were impressed with the characteristic temporal “cluster pattern” of the attacks, coined the term in current use—cluster headache. This headache pattern occurs predominantly in adult men (age range: 20 to 50 years; male-to-female ratio approximately 5:1) and is characterized by a severe consistent unilateral orbital localization. The pain is felt deep in and around the eye, is very intense and nonthrobbing as a rule, and often radiates into the forehead, temple, and cheek—less often to the ear, occiput, and neck. Its denominative feature is the nightly recurrence, between 1 and 2 h after the onset of sleep, or several times during the night for several or more consecutive days; thus “cluster.” Less often, it occurs during the day or early evening, unattended by aura or vomiting. The headache has been called the “alarm clock headache” because it may recur with remarkable regularity each night for periods extending as long as many weeks, followed thereafter by complete freedom for many months or even years. However, in approximately 10 percent of patients, the headache becomes chronic, persisting over days, months, or even years.
There are several associated vasomotor phenomena by which cluster headache can be identified: a blocked nostril, rhinorrhea, injected conjunctivum, lacrimation, miosis, and a flush and edema of the cheek, all lasting on average for 45 min (range: 15 to 180 min). Some of our patients, when alerted to the sign, also report a slight ptosis on the side of the orbital pain; in a few, the ptosis has become permanent after repeated attacks. The homolateral temporal artery may become prominent and tender during an attack, and the skin over the scalp and face may be hyperalgesic.
Most patients arise from bed during an attack and sit in a chair and rock or pace the floor, holding a hand to the side of the head. The pain of a given attack may leave as rapidly as it began or may fade away gradually. Almost always the same orbit is involved during a cluster of headaches as well as in recurring bouts. During the period of freedom from pain, alcohol, which commonly precipitates headaches during a cluster, no longer has the capacity to do so. The picture of cluster headache, including the patient’s nocturnal behavior in response to it, is usually so characteristic that it cannot be confused with any other disease, although those unfamiliar with it may entertain a diagnosis of migraine, trigeminal neuralgia, carotid aneurysm, or temporal arteritis.
A somewhat similar syndrome is produced by the Tolosa-Hunt syndrome of eye pain and ocular motor paralysis caused by dural granuloma at the orbital apex (see further on) and the paratrigeminal syndrome of Raeder, which consists of paroxysms of pain somewhat like that of tic douloureux in the distribution of the ophthalmic and maxillary divisions of the fifth nerve, in association with unilateral Horner syndrome (ptosis and miosis but with preservation of facial sweating). Loss of sensation in a trigeminal nerve distribution and mild weakness of muscles innervated by the fifth nerve are often added. Raeder syndrome is now recognized as a heterogeneous syndrome, some cases being cluster and others caused by a structural lesion in or near the carotid siphon.
Trigeminal Autonomic Cephalgias (Cluster Variants)
Cases of paroxysmal pain behind the eye or nose or in the upper jaw or temple—associated with blocking of the nostril or lacrimation and described in the past under the titles of sphenopalatine (referred to as Sluder’s sphenopalatine neuralgia), petrosal, vidian, and ciliary neuralgia—probably represent variants of cluster headache. A similar head pain may occasionally be confined to the lower facial, postauricular, or occipital areas. Ekbom distinguished yet another “lower cluster headache” syndrome with infraorbital radiation of the pain, an ipsilateral partial Horner syndrome, and ipsilateral hyperhidrosis. There is no evidence to support the separation of these neuralgias as distinct entities, and they have collectively been called trigeminal autonomic cephalgias. They are important, however, because of the frequency of underlying intracranial lesions. In other words, these are not always primary headache disorders. Favier and colleagues collected 4 of their own cases and 27 from the literature to emphasize the range of underlying diseases, including intracranial aneurysms, peritentorial or parasellar meningiomas, or other tumors and nasopharyngeal cancers surrounding the carotid artery. We have encountered a case of Wegener granulomatosis of the soft palate that presented as a paroxysmal trigeminal autonomic neuralgia. The headache syndrome disappeared with cyclophosphamide treatment of the underlying granulomatous disorder.
Chronic paroxysmal hemicrania was the name given by Sjaastad and Dale to a primary headache consisting of rapidly repetitive unilateral form of headache that resembles cluster headache in many respects but has several distinctive features. These are of much shorter duration (2 to 45 min) than cluster and usually affect the temporoorbital region of one side, accompanied by conjunctival hyperemia, rhinorrhea, and in some cases a partial Horner syndrome. Even periorbital ecchymosis may accompany a severe attack. Unlike cluster headache, however, the paroxysms occur many times each day, recur daily for long periods (the patient of Price and Posner had an average of 16 attacks daily for more than 40 years), and, most important, respond dramatically to the administration of indomethacin, 25 to 50 mg tid. Unlike cluster headache, chronic paroxysmal hemicrania is more common in women than in men (ratio of 3:1).
The acronym SUNCT (short-lasting unilateral neuralgiform attacks with conjunctival injection and tearing), another primary headache, has been applied to an episodic condition with attacks of even briefer duration, but otherwise similar to paroxysmal hemicrania in which the supraorbital or temporal pain lasts up to 4 min or so and is frequent; it does not usually respond to indomethacin.
A similar hemicrania but without autonomic features, may be symptomatic of lesions near the cavernous sinus (mainly pituitary adenoma) or in the posterior fossa, but most cases are idiopathic. The typical episode of pain lasts approximately 20 min. Also known is a recurrent nocturnal headache in elderly individuals (“hypnic headache”), as described further on.
The relationship of cluster headache and all of its variants to migraine remains conjectural. No doubt the headaches in some persons have some of the characteristics of both, hence the terms migrainous neuralgia and cluster migraine (Kudrow). Lance and others, however, have pointed out differences that seem important to us: flushing of the face on the side of a cluster headache and pallor in migraine; increased intraocular pressure in cluster headache, normal pressure in migraine; increased skin temperature over the forehead, temple, and cheek in cluster headache, decreased temperature in migraine; and notable distinctions in sex distribution, age of onset, rhythmicity, and other clinical features, but prominently by differences among them in response to specific treatments. Cluster may be triggered in sensitive patients by the use of nitroglycerin and, as mentioned, by alcohol.
The cause and mechanism of the cluster headache syndrome are unknown. Gardner and coworkers originally postulated a paroxysmal parasympathetic discharge mediated through the greater superficial petrosal nerve and sphenopalatine ganglion. These authors obtained inconsistent results by cutting the nerve, but others (Kittrelle et al) reported that application of cocaine or lidocaine to the region of the sphenopalatine fossa (via the nostril) consistently aborts attacks of cluster headache. Capsaicin, applied over the affected region of the forehead and scalp, may have the same effect. Stimulation of the ganglion is said to reproduce the syndrome. Kunkle, on the basis of a large personal experience, concluded that the pain arises from the internal carotid artery, in the canal through which it ascends in the petrous portion of the temporal bone. In the course of an arteriogram, during which a patient with cluster headaches fortuitously developed an attack, Ekbom and Greitz noted a narrowing of the artery that was interpreted as being caused by swelling of the arterial wall, which, in turn, compromised the pericarotid sympathetic plexus and caused the Horner syndrome. This remains to be confirmed.
The cyclic nature of the attacks has been linked to a hypothalamic mechanism that governs the circadian rhythm. At the onset of the headache, the region of the suprachiasmatic nucleus appears to be active on PET (May et al). Hypothalamic activation has also been found in migraine, SUNCT, chronic paroxysmal hemicrania, and hemicrania continua. Moreover, stimulation of the hypothalamus has proved effective, although highly experimental, in stopping chronic cluster headache and SUNCT (see Leone et al and Bartsch et al).
Much was made in the past of the fact that cluster headaches could be reproduced by the intravenous injection of 0.1 mg histamine, but the effect was probably nonspecific. Goadsby has reviewed the pathophysiology of the cluster headache syndrome.
Treatment of Cluster Headache
Inhalation of 100 percent oxygen via mask for 10 to 15 min at the onset of cluster headache may abort the attack, but this is not always practical. Termination of a cycle of cluster can also be achieved with verapamil, starting with 80 mg qid and increasing the dose over days, but electrocardiogram (ECG) monitoring is recommended in the older individual. The usual nocturnal attacks of cluster headache can be treated with a single anticipatory dose of ergotamine at bedtime (2 mg orally) or with possibly lesser efficacy, an equivalent dose of serotonin agonist. Intranasal lidocaine or sumatriptan (or zolmitriptan as for migraine, see above) can also be used to abort an acute attack. In other patients, ergotamine given once or twice during the day, before an attack of pain is expected, has been helpful.
With regard to prevention of cluster headache, if ergotamine and sumatriptan are ineffective or become ineffective in subsequent bouts, many headache experts prefer to use verapamil, up to 480 mg/d. Ekbom introduced lithium therapy for cluster headache (600 mg, up to 900 mg daily), and Kudrow has confirmed its efficacy in chronic cases. Lithium and verapamil may be given together, but lithium toxicity is a frequent problem. A course of prednisone, beginning with 75 mg daily for 3 days and then reducing the dose at 3-day intervals, has been beneficial in many patients. Usually, it can be decided within a week if any one of these medications is effective. In brief, no method is effective in all cases, but the best initial approach probably involves the use of one of the triptan compounds. Rare cases of intractable cluster headache, in which the syndrome persists for weeks or longer without remission, have been treated by partial section of the trigeminal nerve, as described by Jarrar and colleagues, but these ablative measures are now always a last resort, especially when hypothalamic stimulation has been shown to be possibly effective, as mentioned earlier.
Tension-Type Headache (Tension Headache)
This, said to be the most common variety of headache, is usually bilateral, with occipitonuchal, temporal, or frontal predominance, or diffuse extension over the top of the cranium. The pain is usually described as dull and aching, but questioning often uncovers other sensations, such as fullness, tightness, or pressure (as though the head were surrounded by a band or clamped in a vise) or a feeling that the head is swollen and may burst. On these sensations, waves of aching pain are superimposed. These may be interpreted as paroxysmal or throbbing and, if the pain is slightly more on one side, the headache may suggest a migraine without aura. However, absent in tension headache are the persistent throbbing quality, nausea, photophobia, phonophobia, and clear lateralization of migraine. Nor do most tension headaches seriously interfere with daily activities, as migraine does. The onset is more gradual than that of migraine, and the headache, once established, may persist with only mild fluctuations for days, weeks, months, or even years. In fact, this is the only one of the few types of headache that exhibits the peculiarity of being present throughout the day, day after day, for long periods of time for which the term chronic tension-type headache is used. There is often self-acknowledged anxiety and depression, as noted below. Although sleep is usually undisturbed, the headache develops soon after awakening, and the common analgesic remedies have limited effect if the pain is of more than mild to moderate severity.
The incidence of tension headache is certainly greater than that of migraine. However, most patients treat tension headaches themselves and do not seek medical advice. Like migraine, tension headaches are more common in women than in men. Unlike migraine, they infrequently begin in childhood or adolescence but are more likely to arise in middle age and to coincide with anxiety, fatigue, and depression in the trying times of life. In the large series reported by Lance and Curran, about one-third of patients with persistent tension headaches had readily recognized symptoms of depression. They carried out a controlled and blinded trial that demonstrated benefit from amitriptyline even in those patients who were not depressed. In our experience, chronic anxiety or depression of varying degrees of severity is present in the majority of patients with protracted headaches. Migraine and traumatic headaches may, of course, be complicated by tension headache, which, because of its persistence, often arouses fears of a brain tumor or other intracranial disease. However, as Patten points out, not more than one or two patients out of every thousand with tension headaches will be found to harbor an intracranial tumor, and its discovery has been most often incidental (see further on).
In a substantial group of patients with chronic daily headache, the pain, when severe, develops a pulsating quality, to which the term tension-migraine or tension-vascular headache has been applied (Lance and Curran). Observations such as these have tended to blur the sharp distinctions between migrainous and tension headaches in some cases.
For many years, it was thought that tension headaches were a result of excessive contraction of craniocervical muscles and an associated constriction of the scalp arteries. However, it is not clear that either of these mechanisms contributes to the genesis of tension headache, at least in its chronic form. In most patients with tension headache, the craniocervical muscles are quite relaxed (by palpation) and show no evidence of persistent contraction when measured by surface electromyographic (EMG) recordings. Anderson and Frank found no difference in the degree of muscle contraction between migraine and tension headache. However by contrast, using a laser device, Sakai and associates have reported that the pericranial and trapezius muscles are hardened in patients with tension headaches. Nitric oxide has been implicated in the genesis of tension-type headaches, specifically by creating a central sensitization to sensory stimulation from cranial structures. The strongest support for this concept comes from several reports that an inhibitor of nitric oxide reduces muscle hardness and pain in patients with chronic tension headache (Ashina et al). At present, these are interesting but speculative ideas.
Treatment of Tension Headache
Simple analgesics, such as aspirin or acetaminophen or other NSAIDs, may be helpful, if only for brief periods. Persistent or frequent tension headaches respond best to the cautious use of one of several drugs that relieve anxiety or depression such as amitriptyline given as a single dose at night, especially when symptoms of these conditions are present. Stronger analgesic medication should be avoided. Raskin reports success with calcium channel blockers, phenelzine, and cyproheptadine. Ergotamine and propranolol are ineffective unless there are symptoms of both migraine and tension headache. Some patients respond to ancillary measures such as massage, meditation, and biofeedback techniques. Relaxation techniques may be helpful in teaching patients how to deal with underlying anxiety and stress. Gradual withdrawal of daily doses of analgesics, ergotamines, or triptan medications is an important aspect of treating chronic daily headache.
This is a moderately severe cranial pain that remains on one side and may fluctuate in severity. It is accompanied by autonomic features such as conjunctival injection or lacrimation, nasal congestion and runny nose, or ptosis. As mentioned earlier, it is responsive in most instances to indomethacin but escalating doses may be required, or a partial response may be expected from other nonsteroidal agents if gastrointestinal side effects are excessive. The clinical similarities to cluster headache are evident.
New Daily Persistent Headache
This awkward term describes an unremitting generalized headache with a distinct and fairly rapid onset the inception of which can be clearly recalled by the patient. Many cases follow a viral illness, stressful situation or non-cranial surgery as noted in the series reported by Li and Rozen. The IHSS classification requires that it last for over three months. It has a female preponderance but no special clinical, imaging or CSF features. The laterality and cephalic autonomic features of hemicrania continua are lacking. Treatment is largely unsatisfactory but antiepileptic agents may be tried.
HEADACHES ASSOCIATED WITH INCITING EVENTS AND MEDICAL CONDITIONS
In several surveys, headache with onset in the elderly age period was found to be a prominent problem in as many as 1 of 6 persons, and more often to have serious import than headache in a younger population. In a series reported by Pascual and Berciano, more than 40 percent were classified as having tension headaches (women more than men), and there was a wide variety of diseases in the others (posttraumatic headaches, cerebrovascular disease, intracranial tumors, cranial arteritis, severe hypertension, and in our experience, subdural hematomas). Cough-induced headaches and cluster headaches were present in some of the men. New-onset migraine in this age group was a rarity.
Raskin described a headache syndrome in older patients that shares with cluster headache a nocturnal occurrence (hypnic headache). It also may occur with daytime naps. However, it differs in being bilateral and unaccompanied by lacrimation and rhinorrhea. He has successfully treated a number of his patients with 300 mg of lithium carbonate or 75 mg of sustained-release indomethacin at bedtime. The nosologic position of this hypnic headache syndrome is undetermined.
Despite these considerations, the most hazardous cause of headache in the elderly is temporal (cranial) arteritis with or without polymyalgia rheumatica, as discussed further on.
Headache and Other Craniofacial Pain with Psychiatric Disease
The most common cause of generalized persistent headache, both in adolescents and adults, is probably mild depression or anxiety in one of its several forms. A small group of older patients has delusional symptoms involving pain and physical distortion of cranial structures. As the psychiatric symptoms subside, the headaches usually disappear. Odd cephalic pains, for example, a sensation of having a nail driven into the head (clavus hystericus), may occur in hysteria or psychosis and raise perplexing problems in diagnosis. The bizarre character of these pains, their persistence in the face of every known therapy, the absence of other signs of disease, and the presence of other manifestations of psychiatric disease provide the basis for correct diagnosis. Older children and adolescents sometimes have peculiar behavioral reactions to headache: screaming, looking dazed, clutching the head with an agonized look. Usually, migraine is the underlying disorder in these cases, the additional manifestations responding to therapeutic support and suggestion.
Severe, chronic, continuous, or intermittent headaches lasting several days or weeks appear as the cardinal symptom of several cranial posttraumatic syndromes, separable in each instance from the headache that immediately follows head injury that may be due to scalp laceration, cranial or cerebral contusion, or increased intracranial pressure. These cranial pains are also differentiated from the more mundane postconcussive headaches detailed below. The headache of chronic subdural hematoma is deep seated, dull, steady, mainly unilateral and may be accompanied or followed by drowsiness, confusion, and fluctuating hemiparesis. In acute subdural hematomas, we have been impressed with the positional worsening of pain in some patients after lying down or leaning the head to one side. Tentorial hematomas produce the additional feature of pain in the eye. The head injury that gives rise to a subdural hematoma may have been minor, as described in Chap. 34, and forgotten by the patient and family. Typically, the headache increases in frequency and severity over several weeks or months. Patients who have received anticoagulation are particularly at risk. Diagnosis is established by CT or MRI.
Chronic headache is certainly a prominent feature of the postconcussion syndrome, comprising dizziness, fatigability, insomnia, nervousness, irritability, and inability to concentrate. This type of headache and associated symptoms, which resemble the tension headache syndrome, are described fully in Chap. 34, “Craniocerebral Trauma.” The International Headache Society has classified persistence in this context as headache for longer than 3 months after injury. The patient with postconcussion syndrome requires supportive therapy in the form of repeated reassurance and explanations of the benign nature of the symptoms, a program of increasing physical activity, and the use of drugs that allay anxiety and depression. The early settlement of litigation, which is often an issue, works to the patient’s advantage.
Tenderness and aching pain sharply localized to the scar of a long previous scalp laceration or surgical incision represent in a different problem and raise the question of a traumatic neuralgia or neuroma. Tender scars from scalp lacerations may be treated by repeated subcutaneous injections of local anesthetics, which also acts as a diagnostic test.
With whiplash injuries of the neck, there may be unilateral or bilateral retroauricular or occipital pain, probably as a result of stretching or tearing of ligaments and muscles at the occipitonuchal junction or of a worsening of a preexisting cervical arthropathy. Much less frequently, cervical intervertebral discs and nerve roots are involved. However, it is questionable if chronic headache and vague neuropsychiatric symptoms can be attributed to whiplash (see Malleson); nevertheless, the International Headache Society retains post whiplash headache as a category, while noting that it has no typical characteristics.
One should also be alert to headache as a sign of carotid artery dissection after head or neck injury.
It remains a popular notion that headache is a significant symptom in many patients with brain tumor, but it is actually infrequent, particularly as the heralding symptom of a tumor in an adult. While headache is sometimes stated to occur in one-third of brain tumor cases, this is certainly the result of the high frequency of cranial imaging in headache patients. Headache probably only arises if the tumor displaces major cerebral vessels or blocks the flow of CSF, but we have seen exceptions. The pain has no specific features; it tends to be deep seated, usually nonthrobbing (occasionally throbbing), and is described as aching or bursting. However, a major change in the pattern of an accustomed headache syndrome should raise suspicion of a structural lesion in the cranium. Physical activity and changes in position of the head may provoke pain, whereas rest sometimes diminishes it. Nocturnal awakening because of pain occurs in only a small proportion of brain tumor patients and is by no means diagnostic. Most headaches that awaken people at night are cluster-like headaches, hypnic headaches in the elderly, or those caused by caffeine withdrawal. Unexpected forceful (projectile) vomiting may punctuate brain tumor headache in its later stages, particularly in children, or as an early feature if the tumor is in the posterior fossa.
If unilateral, the headache is nearly always on the same side as the tumor. Pain from supratentorial tumors is felt anterior to the interauricular circumference of the skull; from posterior fossa tumors, it is felt behind this line. Bifrontal and bioccipital headaches from tumor coming on after unilateral headaches probably signify the development of increased intracranial pressure or hydrocephalus.
Having stated that headache is not to be equated with brain tumor, one cannot help but be impressed with its frequency in association with colloid cysts, and we have several times stumbled on the diagnosis when an odd, unexplained bilateral headache led to brain imaging. The mechanism of headache in cases of colloid cyst, if such a relationship is valid at all, is not simply one of blocking the flow of CSF at the foramina of Monro, as it is not predicated on the development of hydrocephalus. Restated, the presence of a colloid cyst does not assure that it is explanatory of a headache syndrome; furthermore, many cases of colloid cyst found on imaging or autopsy are not associated with headache. Additionally, Harris described exceptional headaches of paroxysmal type with intra- and periventricular brain tumors, and others have commented on the same type of headache with parenchymal tumors. These are severe headaches that reach their peak intensity in a few seconds, last for several minutes or as long as an hour, and then subside quickly. When they are associated with vomiting, transient blindness, leg weakness causing “drop attacks,” and loss of consciousness, there is a possibility of brain tumor with greatly elevated intracranial pressure. With respect to its onset, this headache almost resembles that of subarachnoid hemorrhage, but the latter is far longer-lasting and even more abrupt in onset. In its entirety, this paroxysmal headache is most typical of the aforementioned colloid cyst of the third ventricle, but it can occur with other tumors as well, including craniopharyngiomas, pinealomas, and cerebellar masses.
Headaches of Temporal Arteritis (Giant Cell Arteritis)
This type of inflammatory disease of cranial arteries is an important cause of headache in older persons (See Also Chap. 33). All of our patients have been older than 55 years of age, most of them older than age 65. From a state of normal health, the patient develops an increasingly intense throbbing or nonthrobbing headache, often with superimposed sharp, stabbing pains. In a few patients the headache has had an almost explosive onset. The pain is usually unilateral, sometimes bilateral, and often localized to the site of the affected arteries in the scalp. The pain persists to some degree throughout the day and is particularly severe at night. It lasts for many months if untreated. The superficial temporal and other scalp arteries are frequently thickened and tender and without pulsation. Jaw claudication and ischemic nodules on the scalp, with ulceration of the overlying skin, have been described in severe cases.
Many of the patients feel generally unwell and have lost weight; some have a low-grade fever and anemia. Usually the sedimentation rate is greatly elevated (>50 mm/h and typically >75 mm/h) but elevation of the C-reactive protein (CRP) level is a more sensitive indicator of this inflammatory condition and is particularly helpful when the sedimentation rate is only mildly elevated. A few patients have a peripheral neutrophilic leukocytosis. Half of patients have generalized aching of proximal limb muscles, reflecting the presence of polymyalgia rheumatica (see Chap. 45, “Polymyalgia Rheumatica”). A relation of temporal arteritis to herpes zoster has been proposed.
The importance of early diagnosis relates to the threat of blindness from thrombosis of the ophthalmic or posterior ciliary arteries. This may be preceded by several episodes of amaurosis fugax (transient monocular blindness). Ophthalmoplegia may also occur but is less frequent, and its cause, whether neural or muscular, is not settled. Masticatory claudication is a specific but not particularly sensitive symptom of cranial arteritis. The large intracranial vessels are occasionally affected, thereby causing stroke. Once vision is lost, it is seldom recoverable. For this reason, the earliest suspicion of cranial arteritis should lead to the administration of corticosteroids and then to biopsy of the appropriate scalp artery. Microscopic examination discloses an intense granulomatous or “giant cell” arteritis. If biopsy on one side fails to clarify the situation and there are sound clinical reasons for suspecting the diagnosis, the other side should be sampled. Arteriography of the external carotid artery branches is probably the most sensitive test but is seldom used, because of its relatively higher risk. Ultrasonographic examination of the temporal arteries may display a dark halo and irregularly thickened vessel walls. This technique has not been incorporated into routine evaluation because its sensitivity has not been established; our own experience suggests that it may miss cases, but it could be useful in choosing the site for biopsy of the temporal artery.
The administration of prednisone, 45 to 60 mg/d in single or divided doses over a period of several weeks, is indicated in all cases, with gradual reduction to 10 to 20 mg/d and maintenance at this dosage for several months or years, if necessary, to prevent relapse. The headache can be expected to improve within a day or two of beginning treatment; failure to do so brings the diagnosis into question. When the sedimentation rate or CRP is elevated, its return to normal, usually over months, is a reliable index of therapeutic response. Whether symptoms or the blood tests are a better guide to reducing the steroid dose is unclear, one should probably be cautious in lowering the medication if the erythrocyte sedimentation rate (ESR) and CRP remain high.
Headaches of Pseudotumor Cerebri (Benign or Idiopathic Intracranial Hypertension)
The headache of pseudotumor cerebri assumes a variety of forms See Chap. 29. Most typical is a feeling of occipital pressure that is greatly worsened by lying down, but many patients have—in addition, or only—headaches of migraine or tension type. Indeed, some of them respond to medications such as propranolol and ergot compounds. None of the proposed mechanisms for pain in pseudotumor cerebri seems to be adequate as an explanation, particularly the idea that cerebral vessels are displaced or compressed, as neither has been demonstrated. It is worth noting that facial pain may also be a feature of the illness, albeit rare. Chapter 29 has a more complete description of the clinical features and treatment.
After successful treatment for pseudotumor, some patients have persistent headaches that have the flavor of migraine or tension headache.
Low-Pressure and Spinal Puncture Headache
These are commonly known to neurologists, as noted earlier in this chapter. They occur after lumbar punctures in approximately 5 percent of procedures. The headache is associated with the greatly reduced pressure of the CSF compartment and probably caused by vertical traction on cranial blood vessels. Neck pain may be a prominent, or the only, feature. Assuming the supine position almost immediately relieves the cranial pain and eliminates vomiting, but a blood-patch procedure may be required in persistent cases. In a limited number of cases, success has been obtained by the use of intravenous caffeine injections. The diagnosis is evident either from a lumbar puncture that demonstrates low or zero pressure or perhaps more definitely, by MRI with gadolinium, which has characteristic enhancement of the pachymeninges (dura). The condition and its treatment are discussed in Chaps. 2 and 29 “Lumbar Puncture Headache” and “Spontaneous Intracranial Hypotension.”
Menstrual (Catamenial) Migraine and Other Headaches Linked to the Hormonal Cycle
The relation of headache to a drop in estradiol levels during the late luteal phase of ovulation was mentioned in “Migraine” above. There it was also indicated that the mechanism is probably more complex. In practice, factors such as sleep deprivation are probably important in triggering perimenstrual headaches. Premenstrual headache, taking the form of migraine or a combined tension-migraine headache, usually responds to the administration of an NSAID begun 3 days before the anticipated onset of the menstrual period; oral sumatriptan (25 to 50 mg qid) and zolmitriptan (2.5 to 5 mg bid) are also equally effective. Manipulation of the hormonal cycle with danazol (a testosterone derivative) or estradiol has also been effective but is rarely necessary.
The management of migraine during pregnancy poses special problems because one wishes to restrict exposure of the fetus to medications. Beta-adrenergic compounds and tricyclic antidepressants may be used safely in the small proportion of women whose headaches persist or intensify during pregnancy. From a limited registry of patients who were given sumatriptan during pregnancy, and from several small trials summarized by Fox and colleagues, no teratogenic effects or adverse effects on pregnancy arose, but serotonin agonist drugs should be used advisedly until their safety is further confirmed. Ergots (DHE) are obviously interdicted because of their capacity to precipitate uterine contractions or labor. For those women who use antiepileptic drugs as a means of headache prevention, it is recommended that the drugs be stopped prior to pregnancy or as soon as it is known that pregnancy has begun.
In the special circumstance of true and debilitating status migrainosus during pregnancy, infusions of magnesium and metoclopramide (in doses previously mentioned in this chapter) are often used but repeated administration and monitoring of blood pressure and tendon reflexes may be needed. This should probably precede resorting to opioids, which may nevertheless become necessary in some cases. In all instances of headache in late pregnancy, the possibilities of toxemia and cerebral venous thrombosis should be considered.
Cough and Exertional Headache
A patient may complain of very severe, transient cranial pain on coughing, sneezing, laughing heartily, lifting heavy objects including weight lifting, stooping, and straining at stool. Pain is usually felt in the front of the head, sometimes occipitally, and may be unilateral or bilateral. As a rule, it follows the initiating action within a second or two and lasts a few seconds to a few minutes. The pain is often described as having a bursting quality and may be of such severity as to cause the patient to cradle his head in his hands, thereby simulating the headache of acute subarachnoid hemorrhage.
Most often this syndrome is a benign idiopathic state that recurs over a period of several months to a year or two and then disappears. Many decades ago, Symonds emphasized the benignity of the condition. In a report of 103 patients followed for 3 years or longer, Rooke found that additional symptoms of neurologic disease developed in only 10. The cause and mechanism have not been determined. During the headache, the CSF pressure is normal. Bilateral jugular compression may induce an attack, possibly because of traction on the walls of large veins and dural sinuses. In a few instances, we have observed this type of headache after lumbar puncture or after a hemorrhage from an arteriovenous malformation.
Patients with cough or strain headache will only occasionally be found to have serious intracranial disease; when present, particularly if a first attack, subarachnoid hemorrhage may be suspected. In other infrequent cases, this type of headache has been traced to lesions of the posterior fossa and foramen magnum, arteriovenous malformation, subdural hematoma, Chiari malformation, or tumor. It may be necessary, therefore, to supplement the neurologic examination by appropriate lumbar puncture, CT and MRI. Far more common, of course, are the temporal and maxillary pains that are caused by dental or sinus disease, which may also be worsened by coughing.
A special variant of exertional headache is “weight-lifter’s headache.” It occurs either as a single event or repeatedly over a period of several months, but each episode of headache may last many hours or days, again raising the suspicion of subarachnoid hemorrhage. The pain begins immediately or within minutes of heavy lifting. If the pain resolves in an hour or less and there is no meningismus or sign of bleeding on the CT, we have foregone lumbar puncture and angiography but have suggested that weight lifting not be resumed for several weeks. Athletes and runners in general seem to suffer exertional headaches quite often in our experience, and the episodes usually have migrainous features.
Indomethacin is usually effective in controlling exertional headaches; this has been confirmed in controlled trials. Useful alternatives are NSAIDs, ergot preparations, and propranolol. In a few of our patients, lumbar puncture appeared to immediately resolve the problem in some inexplicable way.
Chiari Malformation and Headache
All manner of headache has been attributed to Chiari type I malformation (with tonsils descended at least 3 mm below the lip of the foramen magnum), but with limited justification. However, some instances of exertional and Valsalva-induced suboccipital pain can be attributed to this developmental abnormality. In the survey by Pascual and colleagues of 50 patients with Chiari type I malformations, approximately a quarter described a fairly specific pattern of pain consisting of bursting, dull, throbbing, or lancinating discomfort for seconds to far longer following Valsalva-related activities, either in the occipital or frontal region and radiating to one or both shoulders. Only the degree of tonsillar descent correlated with the presence of exertional headache and skull abnormalities such as basilar impression were not clearly associated with this type of headache. It follows that suboccipital decompressive operations for headache in this condition should be undertaken only selectively. Chiari malformation is discussed further in Chap. 37.
Headaches Related to Sexual Activity
Lance (1976) described 21 cases of this type of headache, 16 in males and 5 in females. The headache took one of two forms: one in which pain typical of tension headache developed as sexual excitement increased, and another in which a severe, throbbing, “explosive” headache occurred at the time of orgasm and persisted for several minutes or hours (orgasmic headache). The latter headaches were of such abruptness and severity as to suggest a ruptured aneurysm but the neurologic examination was negative in every instance, as was arteriography in 7 patients who were subjected to this procedure. In 18 patients who were followed for a period of 2 to 7 years, no other neurologic symptoms developed. Characteristically, the headache occurred on several consecutive occasions and then disappeared. In cases of repeated coital headache, indomethacin has been effective. Of course, so-called orgasmic headache is not always benign; a hypertensive hemorrhage, rupture of an aneurysm or vascular malformation, carotid artery dissection, or myocardial infarction may occur during the exertion of sexual intercourse. While there is no authoritative direction, it is justified to perform a spinal tap if a sexual-related headache is the first occurrence of headache in a patient’s history.
This is a severe headache of very abrupt onset and numerous causes, most being less serious than the nature of the symptoms suggest. Of course, the headache of subarachnoid hemorrhage caused by rupture of a saccular (berry) aneurysm is among the most abrupt and dramatic of cranial pains (see Chap. 33). It was in relation to headaches of this nature that the term thunderclap was introduced by Day and Raskin. They attributed the symptoms to an unruptured cerebral aneurysm but the term is now used to denote headache of this description from various causes.
Patients have offered colorful descriptions, such as “being kicked in the back of the head.” Thunderclap headache, as pointed out by Dodick, has been a symptom of pituitary apoplexy, cerebral venous thrombosis, cervical arterial dissection, nonaneurysmal perimesencephalic hemorrhage, or hypertensive crisis (Table 9-4). To this list should be added diffuse idiopathic arterial spasm (Call-Fleming syndrome; see “Diffuse and Focal Cerebral Vasospasm” in Chap. 33) and cerebral vasospasm as the result of the administration of sympathomimetic or serotonergic drugs, including cocaine and the triptan group of medications for the treatment of migraine. The coital and exertional headaches described above may also be considered of this nature. Recurrent thunderclap pain may be particularly indicative of multifocal or diffuse vasospasm, as pointed out by Chen and colleagues, who found this vasculopathy in 39 percent of their patients with recurrent thunderclap pain.
Table 9-4CAUSES OF THUNDERCLAP HEADACHE ||Download (.pdf) Table 9-4CAUSES OF THUNDERCLAP HEADACHE
Cerebral venous thrombosis
Diffuse cerebral vasospasm (Call-Fleming syndrome)
Cocaine and adrenergically active drugs
Perimesencephalic non-aneursymal subarachnoid hemorrhage
Because the pain of thunderclap headache may be indistinguishable from that caused by subarachnoid hemorrhage, even to the extent of being accompanied by vomiting and acute hypertension, the diagnosis is clarified after lumbar puncture and cerebral imaging, and the pain resolves in hours or less. Most cases turn out to be idiopathic. Wijdicks and colleagues confirmed that thunderclap headache is usually a benign condition; among 71 patients followed for more than 3 years they found no serious cerebrovascular lesions. For this reason, these idiopathic thunderclap headaches have been presumed by some workers to be a form of migraine (“crash migraine”). This opinion is based in part on a history of preceding or of subsequent headaches and migrainous episodes in affected individuals; however, in our experience not all of such patients have had migraine in the past. There is a notable tendency for thunderclap headaches to recur as mentioned above.
An intense, generalized, throbbing headache may occur in conjunction with flushing of the face and hands and numbness of the fingers (erythromelalgia). Episodes tend to be present on awakening from sound sleep. This condition, called erythrocyanotic, has been reported in a number of unusual settings: (1) in mastocytosis (infiltration of tissues by mast cells, which elaborate histamine, heparin, and serotonin); (2) with carcinoid tumors; (3) with serotonin-secreting tumors; (4) with some tumors of the pancreatic islets; and (5) with pheochromocytoma. Seventy-five percent of patients with pheochromocytoma reportedly have vascular-type headaches coincident with paroxysms of hypertension and release of catecholamines (Lance and Hinterberger) but the flushing phenomenon has been rare in our experience.
Headache Related to Various Medical Diseases
A cardinal feature of meningitis of varied causes is headache. When accompanied by fever and stiff neck, the diagnosis is almost assured. However, severe headache may occur with a number of infectious illnesses caused by banal viral infections, by organisms such as Mycoplasma, and particularly by influenza. There is often accompanying neck pain and slight stiffness. The suspicion of meningitis is raised, even subarachnoid hemorrhage, but there is no reaction in the CSF (“meningism”). The mild aseptic meningitis that accompanies HIV seroconversion may also be accompanied by headache. When persistent and moderately severe, the headache may be classified with “new daily persistent headache” described above.
Approximately 50 percent of patients with chronic and essential hypertension complain of headache, but the relationship of one to the other is probably coincidental. Minor elevations of blood pressure may be a result rather than the cause of headaches. Severe (accelerated) hypertension, with diastolic pressures of more than 120 mm Hg is, however, associated with headache, and measures that reduce the blood pressure relieve the cranial pain. In preeclampsia, the headaches occur at minor degrees of hypertension or normal levels in a woman who has otherwise low blood pressure. Abrupt elevations of blood pressure, as occur in patients who take monoamine oxidase inhibitors and then ingest tyramine-containing food, can cause headaches that are severe enough to simulate subarachnoid hemorrhage. However, it is the individual with moderately severe hypertension and frequent severe headaches that typically confronts the practitioner. In some of these patients, the headaches are of the common migrainous or tension type, but in others, they defy classification. The acute headache of pheochromocytoma correlates with the rate of increase of blood pressure rather than its absolute value. Curiously, headaches that occur toward the end of renal dialysis or soon after its completion are associated with a fall in blood pressure (as well as a decrease in blood sodium levels and osmolality).
Headaches frequently follow a seizure, having been recorded in half of one large series of epileptic patients analyzed by Schon and Blau but the pain was infrequently severe. In migraineurs, the postseizure headache may reproduce a typical migraine attack.
Experienced physicians are aware of many other conditions in which headache may be a principal symptom. These include fevers of any cause, carbon monoxide exposure, chronic lung disease with hypercapnia (headaches often nocturnal or early morning), sleep apnea, hypothyroidism, thrombocythemia, Cushing disease, withdrawal from corticosteroid medication or alcohol, mountain (altitude) sickness, exposure to nitrates, cyanotic heart disease, occasionally in adrenal insufficiency, and acute anemia with hemoglobin well below 10 g.
No attempt is made here to discuss the symptomatic treatment of headache that may accompany these many medical conditions. Obviously, the guiding principle is to address the underlying disease.
Headache Related to Diseases of the Cervical Spine
Headaches that accompany diseases of the upper cervical spine are well recognized, but their mechanism is obscure and their frequency possibly overestimated. Recent writings have focused on a wide range of causative lesions, such as apophyseal (facet) arthropathy, C2 dorsal root entrapment, calcified ligamentum flavum, hypertrophied posterior longitudinal ligament, and rheumatoid arthritis of the atlantoaxial region. As summarized by Bogduk and Govind, the most credible evidence for this group of disorders comes from systematic injection of anesthetics into cervical structures and effecting complete relief of headache. Even this is not uniformly successful in patients whose cranial pain has been attributed to a cervicogenic mechanism. CT and MRI have divulged a number of these abnormalities. One special variety is discussed further below, under “‘Third Occipital Nerve’ Headache,” and further in Chap. 10.
Trigeminal Neuralgia (Tic Douloureux)
This is a common disorder of middle age and later life, consisting of paroxysms of intense, stabbing pain in the distribution of the mandibular and maxillary divisions (rarely the ophthalmic division) of the fifth cranial nerve (See Chap. 44). The pain seldom lasts more than a few seconds or rarely a minute or two, but it is often so intense that the patient winces involuntarily; hence the term tic. It is uncertain whether the tic is reflexive or quasivoluntary. The paroxysms recur frequently, both day and night, for several weeks or months at a time. Another characteristic feature is the initiation of a jab or a series of jabs of pain by stimulation of certain areas of the face, lips, or gums, as in shaving or brushing the teeth, or by movement of these parts in chewing, talking, or yawning, or even by a breeze—the so-called trigger factors. Sensory or motor loss in the distribution of the fifth nerve cannot be demonstrated, though there are minor exceptions to this rule. In addition to the paroxysmal pain, some patients complain of a more or less continuous discomfort, itching, or sensitivity of restricted areas of the face, features regarded as atypical even though not infrequent.
In studying the relationship between stimuli applied to the trigger zones and the paroxysms of pain, touch and possibly tickle are more likely to be precipitants rather than painful or thermal stimulus. Usually a spatial and temporal summation of impulses is necessary to trigger a paroxysm of pain, which is followed by a refractory period of up to 2 or 3 min.
The diagnosis of tic douloureux rests on the strict clinical criteria enumerated above, so that the condition can be distinguished from other forms of facial and cephalic neuralgia and pain arising from diseases of the jaw, teeth, or sinuses. Most cases of trigeminal neuralgia have no obvious cause (idiopathic), in contrast to symptomatic trigeminal neuralgia, in which paroxysmal facial pain is because of involvement of the fifth nerve by some other disease: multiple sclerosis (may be bilateral), aneurysm of the basilar artery, or tumor (acoustic or trigeminal schwannoma, meningioma, epidermoid) in the cerebellopontine angle. Each of the forms of symptomatic trigeminal neuralgia may give rise only to pain in the distribution of the trigeminal nerve, or it may produce a loss of sensation as well.
Vascular Loop as a Cause of Trigeminal Neuralgia
It has become apparent that a proportion of ostensibly idiopathic cases are caused by compression of the trigeminal roots by a small tortuous branch of the basilar artery. This was originally pointed out by Dandy and brought to greater attention by Jannetta, who has observed it frequently and has devised a procedure that is now widely used to relieve the pain by decompression of the trigeminal root. The offending small vessel is removed from contact with the proximal portion of the nerve (see below). The tortuous vessel can often be visualized by special MRI sequences or by MR angiography but these vessels can be found asymptomatic patients as well. This and other disorders of the fifth nerve, some of which give rise to facial pain, are discussed in Chap. 44.
Carbamazepine is effective in 70 to 80 percent of patients (600 to 1,200 mg/d), but half become tolerant over a period of several years. Other antiepileptic drugs such as phenytoin (300 to 400 mg/d), valproic acid (800 to 1,200 mg/d), clonazepam (2 to 6 mg/d), gabapentin (300 to 900 mg/d or more), pregabalin (150 to 300 mg/d), and carbamazepine in combination with other medications, suppress or shorten the duration and severity of the attacks in most patients for varying times. Baclofen may be useful in patients who cannot tolerate carbamazepine or gabapentin, but it is most effective as an adjunct to one of the anticonvulsant drugs. Capsaicin applied locally to the trigger zones or the topical instillation in the eye of an anesthetic has been helpful in some patients. By temporizing and using these drugs, one may permit a spontaneous remission to occur in perhaps 1 in 5 patients over a year or two.
Many patients with intractable pain, however, come to vascular surgery or a surgical form of root destruction. The vascular decompression procedure, which requires a posterior fossa craniotomy but leaves no sensory loss, has been the most consistent approach. Barker and colleagues reported that 70 percent of 1,185 patients were relieved of pain by repositioning a small branch of the basilar artery that was found to compress the fifth nerve, and this benefit persisted with a recurrence rate of less than 1 percent annually for 10 years. The procedure has been done sometimes without confirmation of a vascular loop by vascular imaging.
A procedure employed more in the past but still finds use, was stereotactically controlled thermocoagulation of the trigeminal roots (Sweet and Wepsic). In recent years, there has been a preference for microvascular decompression on the basis of its sparing of sensation, especially late in the course of the illness (Fields). Several forms of stereotactic radiation are less intrusive alternatives, but their full effect is not evident for months. In practice, an antiepileptic medication is often required for some period of time after any of these procedures, and it must be reinstituted when symptoms reoccur, as they often do.
This syndrome is much less common than trigeminal neuralgia but resembles the latter in many respects. The pain is intense and paroxysmal; it originates in the throat, approximately in the tonsillar fossa, and is provoked most commonly by swallowing but also by talking, chewing, yawning, laughing, etc. The pain may be localized in the ear or radiate from the throat to the ear, implicating the auricular branch of the vagus nerve. For this reason, White and Sweet suggested the term vagoglossopharyngeal neuralgia. This is the main craniofacial neuralgia that may be accompanied by bradycardia and even by syncope, presumably because of the triggering of cardioinhibitory reflexes by afferent vagal pain impulses. There is no demonstrable sensory or motor deficit.
Rarely, tumors, including carcinoma, lymphoma or epithelioma of the oropharyngeal-infracranial region or peritonsillar abscess may give rise to pain that is clinically indistinguishable from glossopharyngeal neuralgia.
For idiopathic glossopharyngeal neuralgia, a trial of carbamazepine, gabapentin, pregabalin, or baclofen may be useful. If these are unsuccessful, the conventional surgical procedure had been to interrupt the glossopharyngeal nerve and upper rootlets of the vagus nerve near the medulla but recent observations suggest that a vascular decompression procedure similar to the one used for trigeminal neuralgia and directed to a small vascular loop under the ninth nerve relieves the pain in a proportion of patients.
Cranial Herpes Zoster and Postherpetic Neuralgia
The common pain and herpetic eruption caused by herpes zoster infection of the gasserian ganglion are practically always limited to the first division (herpes zoster ophthalmicus). Ordinarily, the rash appears within 4 to 5 days or less after the onset of the pain, thereby making the clinical diagnosis difficult; however, treatment should be instituted (see below) based on the clinical likelihood of zoster infection. If the eruption does not appear, some cause other than herpes zoster will almost invariably declare itself; nevertheless, a few cases have been reported in which the characteristic location of pain with serologic evidence of herpes zoster infection was not accompanied by skin lesions.
The acute discomfort associated with the herpetic eruption usually subsides after several days or weeks, or it may linger for several months. It is mostly in the elderly that the pain becomes chronic and intractable. Usually it is described as a constant burning, with superimposed waves of stabbing pain, and the skin in the territory of the preceding eruption is exquisitely sensitive to the slightest tactile stimuli, even though the threshold of pain and thermal perception is elevated. This unremitting postherpetic neuralgia of long duration represents one of the most difficult pain problems with which the physician must deal. Some relief may be provided by application of capsaicin cream, use of a mechanical or electrical cutaneous stimulator, or administration of one of the antiepileptic drugs.
Neuralgia associated with a vesicular eruption caused by the herpes zoster virus may affect the external auditory meatus and pinna and sometimes of the palate and occipital region—with or without deafness, tinnitus, and vertigo—is combined with facial paralysis. This syndrome, since its original description by Ramsay Hunt, has been known as geniculate herpes, and also Ramsay Hunt syndrome (see also Chap. 44). It is clear that the skin of the external ear canal, tympanic membrane and in some patients, the skin behind the ear are supplied by somatic sensory branches that travel with the chorda tympani and greater superficial petrosal nerves and have their cell bodies in the geniculate ganglion.
Treatment with acyclovir, along the lines indicated in Chap. 32, will shorten the period of eruption and the acute pain, but the drug does not prevent its persistence as a chronic pain. There is little data upon which to judge the utility of corticosteroids but they are generally not used (whereas they do provide benefit in Bell’s palsy and antiviral agents are not clearly useful).
Antidepressants such as amitriptyline and fluoxetine are helpful in some patients, and Bowsher has suggested, on the basis of a small placebo-controlled trial, that treatment with amitriptyline during the acute phase may prevent persistent pain. The use of preemptive measures, such as gabapentin or pregabalin administered at the outset, may be effective but a properly performed clinical trial is lacking. The addition of amitriptyline up to 75 mg at bedtime has proved to be a useful measure. Probably equivalent results are obtained by a combination of valproic acid and an antidepressant, as reported by Raftery. King has reported that two 325-mg aspirin tablets crushed and mixed with cold cream or chloroform (15 mL) and spread over the painful zone on the face or trunk relieved the pain for several hours in most patients with postzoster neuralgia. Ketamine cream has been suggested as an alternative. Extensive trigeminal rhizotomy or other destructive procedures should be avoided, as these surgical measures are not for long successful and may lead to a superimposed diffuse refractory dysesthetic component on the original neuralgia (anesthesia dolorosa).
Under the heading of “primary trochlear headache,” Yanguela and colleagues have described a periorbital pain that emanates from the superomedial orbit in the region of the trochlea (the pulley of the superior oblique muscle). Most of their patients were women. The pain was worsened by adduction and (paradoxically for the superior oblique) upgaze of the globe on the affected side, in the direction of action of the superior oblique muscle. The authors describe a diagnostic method of examination that begins by having the patient look downward so that the trochlea can be palpated and compressed; the patient then looks upward, eliciting or exaggerating the pain, while the examiner continues compression. Injection of the trochlea with corticosteroids relieved the pain in almost all of these patients. The authors made a distinction between primary trochlear headache and “trochleitis,” which seems to us an ambiguous difference. There is no limitation of ocular movement or autonomic change and imaging of the orbit is normal. This syndrome, with which we have no experience, brings to mind the entity of the Brown syndrome of trochlear entrapment with diplopia and pain (Chap. 13). The above authors were also of the opinion that the trochlea may be a trigger point for migraine.
Pain localized in and around one ear is occasionally a primary complaint. It is commonly the incipient symptom of Bell’s palsy or an outbreak of shingles but there are a number of different causes and mechanisms. During neurosurgical operations in awake patients, stimulation of cranial nerves V, VII, IX, and X causes ear pain, yet interruption of these nerves usually causes no or limited demonstrable loss of sensation in the ear canal or the ear itself (superficial sensation in this region is supplied by the great auricular nerve, which is derived from the C2 and C3 roots). The neurosurgical literature cites examples of otalgia that were relieved by section of the nervus intermedius (sensory part of VII) or of nerves IX and X. In otalgic cases, one is also prompted to search for a nasopharyngeal tumor, vertebral artery aneurysm or dissection or to anticipate an outbreak of zoster as mentioned. Formerly, lateral sinus thrombosis was a common cause in children. When these possibilities are eliminated by appropriate studies, there always remain examples of primary idiopathic otalgia, lower cluster headache, and glossopharyngeal neuralgia. Some patients with migraine have pain centered in the ear region and occiput, but we have never observed a trigeminal neuralgia in which the ear was the predominant site of pain. Occasionally, temporomandibular joint disease is the cause (see below).
Paroxysmal pain may occur in the distribution of the greater or lesser occipital nerves (suboccipital, occipital, and posterior parietal areas). While tenderness may be localized to the region where these nerves cross the superior nuchal line, there is only questionable evidence of an occipital nerve lesion at this site. The finding of hypesthesia in the distribution of the occipital nerves makes the possibility of an entrapment neuropathy more convincing. Carbamazepine or gabapentin may provide some relief. Blocking the nerves with lidocaine may abolish the pain and encourage attempts to section one or more occipital nerves or the second or third cervical dorsal root, but the results of the sectioning procedure have had variable success, and several such patients who had these procedures were later referred to us with disabling anesthesia dolorosa. Experts advise repeated injections of local anesthetic agents and the use of steroids, botulinum toxin, and analgesic and anti-inflammatory drugs. The pain at times may be difficult to distinguish from that arising in the upper three cervical facet joints, one type of which is discussed below. The approach of treating migraine by injection of the occipital nerves, mentioned earlier, is controversial.
“Third Occipital Nerve” Headache
This condition, a unilateral occipital and suboccipital ache, may be a prominent symptom in patients with neck pain, particularly after neck injuries (a prevalence of 27 percent, according to Lord et al). Bogduk and Marsland attribute it to a degenerative or traumatic arthropathy involving the C2 and C3 facet joints with impingement on the “third occipital nerve” (a branch of the C3 dorsal ramus that crosses the dorsolateral aspect of the facet joint. Elimination of the neck pain and headache by percutaneous blocking of the third occipital nerve near the facet joint under fluoroscopic control is diagnostic and temporarily therapeutic. More sustained relief (weeks to months) has been obtained by radiofrequency coagulation of the nerve or steroid injections in and around the joint. NSAIDs also may provide some relief.
Carotidynia and Extracranial Artery Dissection
Carotidynia was coined by Temple Fay in 1927 to designate a special type of cervicofacial pain that could be elicited by pressure on the common carotid arteries of patients with atypical facial neuralgia. Compression of the artery in the neck in these patients, or mild electrical stimulation at or near the bifurcation, produced a dull ache that was referred to the ipsilateral face, ear, jaws, and teeth or down the neck. This type of carotid sensitivity occurs as part of cranial (giant cell) arteritis and of the rare condition known as Takayasu arteritis (Chap. 33), and during attacks of migraine or cluster headache. It has also been described with displacement of the carotid artery by tumor and dissecting aneurysm of its wall; among these causes, the last is of greatest concern. The idiopathic variety of carotidynia may have to do with a swelling or inflammation of the tissue surrounding the carotid bifurcation, a change that has been demonstrated on MRI by Burton and colleagues, but the problem has been seen most frequently in migraineurs.
Roseman has described a variant of carotidynia that has a predilection for young adults. This syndrome takes the form of recurrent, self-limited attacks of pain and tenderness at the carotid bifurcation lasting a week or two. Dissection of the carotid artery, as discussed below, is always a concern. During the attack, aggravation of the pain by head movement, chewing, and swallowing is characteristic. This condition is treated with simple analgesics. Yet another possible variety of carotidynia appears at any stage of adult life and recurs in attacks lasting minutes to hours in association with throbbing headaches indistinguishable from common migraine (Raskin and Prusiner). This form responds favorably to the administration of ergotamine and other drugs that are effective in the treatment of migraine.
Although most pain of carotid or vertebral artery dissection is localized to the site of injury in the anterior or posterior neck, Arnold and colleagues have emphasized the frequency with which ipsilateral headache, and not neck pain, was the sole feature. Some had a paroxysmal (“thunderclap”) onset but most had throbbing and progressive pain over days, sometimes bilaterally. The combination of focal neck pain and localized headache over an eye is particularly suggestive of carotid dissection and, of course, if there are corresponding symptoms of fluctuating or static regional brain ischemia, Horner syndrome, or lower cranial nerve palsies, the diagnosis is likely.
Temporomandibular Joint Pain (Costen Syndrome)
This is a form of craniofacial pain from dysfunction of one temporomandibular joint. Malocclusion because of ill-fitting dentures or loss of molar teeth on one side with alteration of the normal bite may lead to distortion of and ultimately degenerative changes in the joint and to pain in front of the ear, with radiation to the temple and over the face (see Guralnick et al). Most patients, according to Scrivani and colleagues report deviation of the mandible to the affected side on jaw opening and clicking noises emanating from the joint. Locking of the jaw in either the open or closed position is another feature. The diagnosis is supported by the findings of tenderness over the joint, crepitus on opening the mouth, and limitation of jaw opening. The favored diagnostic maneuver involves palpating the joint from its posterior aspect by placing a finger in the external auditory meatus and pressing forward. The diagnosis can be made with some confidence only if this entirely reproduces the patient’s pain. CT and plain films are rarely helpful, but effusions have been shown in the joints by MRI. Management consists of careful adjustment of the bite by a dental specialist. Small doses of amitriptyline at bedtime may be helpful. In our experience, most of the putative diagnoses of Costen syndrome that reach the neurologist have been uncertain, and the number of headaches and facial pains that are attributed to “temporomandibular joint dysfunction” is probably excessive, especially if judged by the response to treatment. The temporomandibular joint may also be the source of pain when involved with rheumatoid arthritis and other connective tissue diseases.
Facial Pain of Dental or Sinus Origin
Maxillary and mandibular discomfort is a common effect of nerve irritation from deep caries, abscess, dental pulp degeneration, or periodontal disease. The pain of dental nerve origin is usually most severe at night, slightly pulsating, and often associated with local tenderness at the root of the tooth in response to heat, cold, or pressure. The diagnosis can be confirmed by infiltrating the base of the tooth with lidocaine, and the pain is eradicated by proper dental management.
Trigeminal neuritis following dental extractions or oral surgery is another vexing problem. There may be sensory loss in the tongue or lower lip and weakness of the masseter or pterygoid muscle.
Sometimes the onset of “atypical facial pain” (see below) can be dated to a dental procedure such as tooth extraction, and, as usually happens, neither the dentist nor the neurologist is able to find a source for the pain or any malfunction of the trigeminal nerve. Roberts and coworkers, as well as Ratner and associates, have pointed out that residual microabscesses and subacute bone infection account for some of these cases. They isolated the affected region by using local anesthetic blocks, curetted the bone, and administered antibiotics, following which the pain resolved. The removed bone fragments showed vascular and inflammatory changes and infection with oral bacterial flora, but there was no control material.
Facial Pain of Uncertain Origin (Idiopathic, “Atypical” Facial Pain)
There remains, after all the aforementioned facial pain syndromes, a fair number of patients with pain in the face for which no cause can be found. These patients are most often young women, who describe the pain as constant and unbearably severe, deep in the face, or at the angle of cheek and nose, and unresponsive to all varieties of analgesic medication. Because of the failure to identify an organic basis for the pain, one is tempted to attribute it to psychologic or emotional factors. Depression of varying severity is found in some. Some such patients, with or without depression, respond to tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRI) medications. Differentiated from this group is the condition of trigeminal neuropathy with facial numbness, described in Chap. 44.
Facial pain of the “atypical type,” like other chronic pain of indeterminate cause, requires close observation of the patient, looking for lesions such as nasopharyngeal carcinoma or apical lung carcinoma to become apparent. The pain can be managed by the conservative methods outlined in the preceding chapter and not by destructive surgery. Antidepressants may be helpful, especially if the patient displays obsessive characteristics in relation to the pain; some European neurologists favor clomipramine for various facial and scalp pains.
Other Rare Types of Facial Pain
Neuralgia may arise in the terminal branches of the trigeminal, ciliary, nasociliary, and supraorbital nerves; some of which have already been mentioned. Some of these are vague entities at best and merely descriptive terms given to pains localized around the eye and nose. The Tolosa-Hunt syndrome of pain behind the eye and granulomatous involvement of some combination of cranial nerves III, IV, VI, and ophthalmic V, responsive to steroids, is discussed in Chap. 44.
A kind of reflex sympathetic dystrophy of the face is postulated as another rare form of persistent facial pain that may follow dental surgery or penetrating injuries to the face. It is characterized by severe burning pain and hyperpathia in response to all types of stimuli. Sudomotor, vasomotor, and trophic changes are lacking, unlike causalgia that affects the limbs. Nevertheless, this form of facial pain is said to respond to repeated blockade or resection of the stellate ganglion.
Under the title of neck–tongue syndrome, Lance and Anthony have described the occurrence of a sharp pain and tingling in the upper neck or occiput with numbness of the ipsilateral half of the tongue on sudden rotation of the neck. They attribute the syndrome to stretching of the C2 ventral ramus, which contains proprioceptive fibers from the tongue; these fibers run from the lingual nerve to the hypoglossal nerve and thence to the second cervical root.
A problem that has gone by the self-evident name burning mouth syndrome (stomatodynia) occurs mainly in middle-aged and older women, as commented in Chap. 11. The tongue or other oral sites may be most affected or the entire oral mucosa may burn. A few patients are found to have diabetes, vitamin B12 deficiency, or Sjögren syndrome as possible causes. A hint to the last diagnosis is the inability to feel food in the mouth. The oral mucosa is normal when inspected, and no one treatment has been consistently effective, but gabapentin combined with antidepressants or clonazepam may be tried (see the review by Grushka et al). One of our patients with a limited form of this condition, which affected only the upper palate and gums, benefited from dental nerve blocks with lidocaine.
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