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Headache is probably the most common human malady and the most prevalent neurological symptom associated with any disease. As a symptom for which medical advice is sought. Headache is a major social and economic burden for society and is a leading cause for the use of over-the-counter medications. Although headache is usually a benign, primary medical disorder, it can be secondary-that is, a symptom of a serious and life-threatening disease.

According to The International Headache Society (IHS) headache may be associated with trauma, vascular disorders, nonvascular intracranial disorders, substance use or withdrawal, noncephalic infections, metabolic disorders, disorders of facial or cranial structures, and cranial neuralgias and headaches for which no clear classification has yet been determined.

Foremost in diagnosis is the determination of whether the headache is secondary or primary in nature. This determination can be facilitated by a specific approach to clinical history taking that attempts to define the headache's duration, cause, location, and character. The patient's response to the question of duration (i.e., "How long have you had the headache?") may tell immediately whether the headache is chronic, lasting years and suddenly becoming worse (e.g., tension-type headache); whether it is a chronic paroxysmal headache (e.g., migraine), occurring perhaps weekly for several years; or whether it is the first attack of this type of headache that the patient has experienced. A headache that began five to six weeks before consultation and has increased in severity may imply increased intracranial pressure. Headache of so-called thunderclap onset may indicate a sentinel headache caused by subarachnoid hemorrhage. Headache that occurs on waking may occur in such diverse conditions as cluster headache, migraine, hypertension, cerebral neoplasia, and cerebrovascular disease.

The question of causation (i.e., "What do you think is causing the headache?") may elicit key points, such as headache precipitated by activity, straining, increased blood pressure, or sudden head turning, all of which may indicate increased intracranial pressure. Headache occurring during sexual intercourse should alert the physician to the possibility of subarachnoid hemorrhage, but it may turn out to be coital cephalalgia. A relation to stress, fatigue, concentration, social problems, excitement, hunger, attitude, eating chocolate, and use of oral contraceptives or estrogens may indicate a migraine syndrome. A history of fever or the ingestion of exogenous toxins, caffeine, alcohol, tobacco, and nitrates suggests headache of chemical, toxic, or metabolic origin.

The question of location (i.e., "Where is the headache?") is important. Headache caused by infratentorial disease will most often be localized to the occipital region. The frontal region is usually involved if the problem is supratentorial. However, pain from infratentorial structures may be referred to frontal regions and vice versa. For example, structural lesions obstructing the circulation of cerebrospinal fluid in the infratentorial ventricular system can also produce frontal headache secondary to hydrocephalus of the lateral ventricles. A hemicranial localization of the pain may suggest migraine. A pulsatile retroorbital pain may indicate an expanding aneurysm around the circle of Willis, arterial dissection, cluster headache, or inflammatory lesions of the orbital structures. Chronic pain experienced over the vertex or in a hatband distribution may suggest muscle contraction headache.

The question of the headache's character (i.e., "What is the headache like?") is the most difficult for the patient to answer and for the examiner to interpret. For example, although headache severity is a subjective response, information on increasing or decreasing severity is very valuable. Headache of a pulsatile nature (i.e., strictly timed with the pulse) is highly indicative of a vascular origin. A throbbing pain that is not timed with the pulse is less specific. Stabbing, ice pick-like pains may be of vascular origin; when localized behind the eye, such pain may suggest cluster headache or structural disease. Steady pain is less likely to be vascular in origin but can be if it is localized. Steady pain of increasing severity over weeks, if generalized, may indicate increasing intracranial pressure. Another characteristic feature of intracranial pressure is the expanding nature of headache enhanced by activities such as bending, stooping, coughing, defecation, and sexual intercourse. A constant viselike gripping pain or a dull-pressure pain may indicate tension-type headache.

Symptoms that are specifically associated with each headache type are important diagnostic aids. Visual symptoms are common features of migraine and may include scintillating phenomena, teichopsia, hemianopsia field defect, scotoma, and photophobia. Complaints of rapid and progressive impairment of vision may occur in association with papilledema caused by a mass or increased intracranial pressure of some other cause. Persistent visual field defects, a serious complication in patients with temporal arteritis, may be heralded by local temporal pain on the affected side. Another visual symptom of potentially serious significance is diplopia, particularly when it is persistent.

Vomiting is a potentially serious symptom. Vomiting often accompanies severe migraine headache; if it alleviates the headache, it can be a diagnostic feature of migraine. On the other hand, projectile vomiting associated with headache may indicate increased intracranial pressure, or it can be a symptom of a systemic disorder associated with headache, such as fever, toxic reactions, allergic reactions, and sunstroke.

Headache with persistent symptoms of paresis, paralysis, ataxia, or sensory disturbance may indicate structural lesions and should always be regarded as serious. On the other hand, episodic recurrence of such symptoms may indicate that the associated headache is a subclassification of migraine.

Direct questions should be asked about any soreness, tenderness, and stiffness of the head and neck structures. The vascular headache of temporal arteritis may be associated with soreness and tenderness over one temple. Dysfunctional temporomandibular joints may be painful. Localized facial pain may be a symptom of sinusitis. Neck stiffness and soreness may be an early sign of meningeal irritation or, in rare instances, herniation of the cerebellar tonsils. Pain and discharge from the ear may indicate infection. A bloody aural discharge occurs after head injury or skull fracture with complicating hemorrhage. Ocular symptoms often associated with head pain include photophobia during migraine, lacrimation during cluster headache, and red eye with local pain in acute glaucoma or iritis. Nasal symptoms include nasal stuffiness associated with vascular headache of migraine type, particularly cluster headache. A nasal discharge may also be associated with cluster headache or sinusitis.

The importance of a painstaking history cannot be emphasized enough, because at the end of the clinical examination, the physician is often left solely with historical features with which to make the diagnosis of headache. Nevertheless, a negative examination is as important to the diagnosis of primary headache as a positive examination is to the diagnosis of headache from an intracranial neoplasm. There are almost always positive findings to be made in the examination of a patient with headache-for example, the behavioral reaction of the patient to pain. A patient who complains of severe headache but is sitting up and discussing it in an animated fashion usually has a less serious cause of the pain than a patient who is lying motionless in a darkened room or is vomiting. Although most patients with head pain usually lie still, patients who have meningeal irritation caused by subarachnoid hemorrhage or infection may exhibit extreme restlessness, the bedclothes being found awry with the patient sprawled across the bed.

Appropriate and thorough examination of the head and neck may reveal that the cause of the headache is an abnormality of pericranial structures. Key structures likely to be involved in the differential diagnosis of headache are the temporomandibular joint, sinuses, teeth, and muscles of the head and neck. Trapezius muscle spasm can be a direct cause of head pain or secondary to intracranial mischief. Testing for nuchal rigidity should always be done. Tenderness of the superficial temporal artery is the hallmark of arteritis. Tenderness of the internal carotid artery occurs in carotidynia. Headache can be a presenting symptom of acute glaucoma, which can cause rapidly progressive blindness. Enlargement of lymph nodes in the occipital canal can compress the occipital nerve and produce a pulsatile headache. Infection in the bone or scalp causing localized headache is usually accompanied by enlargement of regional nodes. Tubercular nodes (e.g., tuberculous cervical lymphadenitis) can be associated with a painful ophthalmoplegia or Tolosa-Hunt syndrome. Blood in the external acoustic meatus can accompany headache from an intracranial hematoma secondary to head injury, and a boggy mass in the region of the temporal muscle can accompany headache from an extradural hematoma.

Auscultation of the neck may reveal bruits of atherosclerotic origin in the extracranial arteries. Auscultation of the eyes may reveal the bruit of a cavernous sinus fistula. Auscultation of the head may reveal the bruit of an arteriovenous malformation.

A dermatologic examination can sometimes be helpful in the diagnosis of headache and head pain. Rashes-particularly on the head and neck-may indicate that a systemic disease, such as herpes zoster or herpes simplex, is causing the headache. The skin directly over temporal arteritis may be edematous and inflamed. The skin of patients with migraine may be pale, cold, and clammy in a hemifacial distribution.

An elevated temperature may indicate a systemic cause of the headache and is experienced on occasion by some patients with acute migraine. The measurement of blood pressure is vital to the differential diagnosis of headache and should be recorded from both arms and in erect and supine positions because postural hypotension can produce a characteristic low-pressure headache.

A complete neurologic examination is important, particularly when the history suggests involvement of the central nervous system and when full examination of other systems has been unrevealing. Symptoms of confusion or depression of consciousness indicate a high probability of a serious neurologic lesion. Ophthalmoscopic examination is vital, especially to evaluate the optic disk for papilledema, which indicates increased intracranial pressure. Bitemporal field deficit in a patient with severe frontotemporal headache can be caused by an expanding pituitary adenoma. Scotomas or hemianopic field defects may indicate brain tumor, arteriovenous malformation, or expanding aneurysm. Ischemia and hemorrhagic cerebrovascular disease both present with headache and visual field defects-symptoms that also commonly occur in migraine, complicating the differential diagnosis.

Ophthalmoplegia should always be considered significant. Ophthalmoplegic migraine is rare, but unilateral third nerve palsies and bilateral sixth nerve palsies are frequently related to aneurysms of the cerebral vasculature or to increased intracranial pressure and brain herniation. Unilateral ophthalmoplegia and sensory loss in the first division of the fifth cranial nerve in association with unilateral retro-orbital headache may be caused by a superior orbital fissure syndrome, painful ophthalmoplegia, or Tolosa-Hunt syndrome. Unilateral Horner's syndrome and headache may indicate carotid artery dissection. Miosis and excessive sweating may indicate posttraumatic dysautonomic cephalalgia.

If symptoms and signs emerge that indicate structural lesions within the CNS, neurologic examination should be intensified to localize lesions and identify a cause.

The general diagnostic categories into which headache may fall include the following: (1) secondary headache with symptoms and signs of a systemic disorder, (2) primary headache with symptoms and signs of a CNS disorder, and (3) primary headache without neurologic deficits.

Varieties of headache secondary to a systemic disorder include headache of intracranial origin (produced by systemic conditions, such as acute pressor reaction or fever), extracranial secondary headache (e.g., sinusitis and temporomandibular joint problems), and nonmigrainous vascular headache (e.g., simple intracranial vasodilatation secondary to toxic or metabolic factors).

Patients with headache and associated neurologic deficit can be placed in three general subcategories, including (1) intracranial nonvascular headache, (2) nonmigrainous vascular headache, and (3) primary headache of migraine type [see Primary Headaches, Migraine, below]. The more serious and life-threatening causes of headache fall within the diagnostic conditions of the first two categories.

The major differential diagnoses in cases of migraine with neurologic deficit include arteriovenous malformations; transient ischemic attacks; and stroke resulting from cerebrovascular disease, symptomatic epilepsy, and neoplasia. Subarachnoid hemorrhage with vasospasm, though rare, should also be considered. In younger persons, the most likely structural lesion is an arteriovenous malformation. In cases of migraine headache accompanied by third, fourth, or sixth cranial nerve paresis (either as a prodrome or during the headache phase), the differential diagnosis includes aneurysmal dilatation of the cerebral arteries, particularly the internal carotid artery or the posterior communicating artery. Visual field defects that occur during migraine can also be presenting symptoms of atherosclerotic disease of the extracranial cerebral vasculature, cardiogenic embolism, ischemic optic neuropathy, antiphospholipid antibody syndrome, and temporal arteritis.

The headache of increased intracranial pressure is usually generalized, with a so-called expanding quality. Although episodic at first, the headache progresses over a short time to become more frequent and then continuous. Such headaches occur in the early morning and may awaken the patient from sleep. They worsen with actions that further increase pressure, such as bending, stooping, and the Valsalva maneuver. Associated features include spontaneous vomiting. Physical examination may reveal papilledema, visual loss, false localizing ocular paresis (e.g., sixth nerve palsy), and neurologic abnormalities caused by direct lesion involvement of brain structures.

Idiopathic intracranial hypertension, also known as pseudotumor cerebri, may present in a similar manner. It is caused by elevation of CSF pressure without structural disease and is associated with obesity, thyroid and parathyroid disease, hypoadrenalism, iron deficiency anemia, and the use of certain drugs (e.g., tetracycline, vitamin A, and oral contraceptives). Visual loss is often severe; occasionally, it is an indication for emergency optic nerve sheath decompression to prevent permanent damage. Otherwise, treatment consists of regular spinal tap and drugs, such as acetazolamide or, if symptoms are severe, glucocorticoids, in an attempt to reduce head pain and protect vision as a temporary measure. Over the long term, weight loss alone may result in cure.

The primary headaches include migraine with and without aura, cluster headache, tension-type headache, and conversion headache . The differential diagnosis of primary headache is most difficult when the headache presents for the first time in an elderly patient, in which case intensive investigation may be necessary.

Estimates of the prevalence of migraine have varied widely. Recent epidemiological studies have estimated that in the United States, migraine occurs in 18 percent of women and six percent of men. It peaks in prevalence in persons 30 to 45 years of age. The prevalence in children is 2. 5 percent from seven to nine years of age, 4.6 percent from 10 to 12 years of age, and 5. 3 percent from 13 to 15 years of age. Previous studies generally found that in adults, migraine with aura is less prevalent than migraine without aura. However, the true prevalence rates of migraine with aura are difficult to assess by standard epidemiological means; it can be difficult to distinguish aura symptoms on the basis of questionnaires, and subject recall of symptoms may be less than perfect. Given these limitations, the overall prevalence of migraine with aura is probably around four percent-distinctly less than the prevalence of migraine without aura in women and about equal to that in men.

Migraine is now generally considered a unique brain response with a threshold and multiple trigger factors. Migraine attacks constitute a symptom of disordered brain function, just as a seizure can be symptomatic of a functional disturbance or structural abnormality in the brain. Insight into what formulates the threshold for the migraine attack should provide evidence of the true cause of migraine, which is as yet unknown. From the observation of spreading oligemia in migraine attacks, it has been suggested that Leao's spreading cortical depression can account for the clinical symptoms of migraine with aura. This theory suggests that the migraine attack is initiated by a burst of neuronal activity, resulting in a slow neuronal depolarization, which may spread into contiguous brain regions in a manner resembling spreading cortical depression; however, this theory requires more clinical proof. Slow direct current shifts have yet to be seen in the human brain in vivo because there are no electrophysiological techniques to detect such phenomena. Magnetoencephalographic measurements made in the occipital cortex of patients with migraine have been shown to be similar to magnetoencephalographic measurements of spreading cortical depression in the animal brain. There is some electrophysiological, hemodynamic, and metabolic evidence that brain function of migraine-susceptible persons differs from normal function between attacks. Taken together, these studies are persuasive that a state of central neuronal hyperexcitability may exist between migraine attacks, particularly in the occipital cortex.

The headache of a migraine attack is attributed to activation of the trigeminovascular system. The mechanisms remain to be determined but may be related to cortical events (see below). It is known that during a migraine attack, peptides are released locally from sensory axons (involving an axon reflex) of the trigeminal nerve. These sensory axons supply certain extracranial arteries, meningeal tissues, dural arteries, and the dural sinuses. The neuropeptide release may produce a pain-sensitive state (i.e., neurogenic inflammation) and promote local vasodilatation . Calcitonin gene-related peptide is released into the jugular vein during a migraine attack, and this release is blocked by the antimigraine drug sumatriptan . Sumatriptan, acting presynaptically, blocks the neuropeptide-mediated inflammatory response after trigeminal stimulation and may also block transmission in trigeminal neurons. The direct vasoconstrictive action of sumatriptan may be another mechanism by which this drug alleviates headache. Alternatively, it may be that the trigeminal system is activated centrally rather than peripherally. Recent evidence from positron emission tomographic measurements supports the theory of activation of pontomesencephalic centers, where serotoninergic and noradrenergic systems exert an influence on trigeminal and central pain pathways.

The most frequently encountered migraine syndromes include typical headache without aura of neurologic deficit (previously termed common migraine) and headache associated with aura of neurologic deficit (previously termed classic migraine). Patients can have migraine headache both with and without neurologic aura at any time during the natural history of their disorder. They may also suffer neurologic deficit of migraine type without headache (migraine sine hemicrania).

In migraine with aura, visual disturbances account for well over half of the transient neurologic manifestations. Most often, these disturbances consist of positive phenomena, such as stars, sparks, photopsia, complex geometric patterns, and fortification spectra. These positive phenomena may leave in their wake negative phenomena, such as scotoma or hemianopsia. The symptoms are characteristically slow in onset and progression; however, onset can occasionally be abrupt. Visual symptoms sometimes progress to visual distortion or misperception, such as micropsia or dysmetropsia. The patterns of symptoms indicate the spread of neurologic dysfunction from the occipital cortex into the contiguous regions of the temporal or parietal lobes.

Somatosensory symptoms are the second most common manifestations and are characteristically distributed around the hand and lower face. Less frequently, the symptoms include aphasia, hemiparesis, or clumsiness on one side. In most cases, a slow, marching progression is characteristic. The anatomic distribution of the neurologic deficit often overrides vascular boundaries. Some patients experience visual distortions of body image (i.e., metamorphopsia) and other visual illusions that occur in the Alice in Wonderland syndrome. Transient global amnesia can occur as a migraine aura but only in rare instances.

The aura usually lasts approximately 30 minutes before subsiding and is followed by a brief interlude of normality before the onset of headache that is unilateral or bilateral, pulsating, moderate to severe in intensity, and exacerbated by physical activity. In some instances, the aura continues into the headache phase. The headache may subside in as little as six hours or may last as long as three days. The longer duration is more typical of the headache of migraine without aura, which has similar features to migraine with aura but is characteristically moderate to severe in intensity and more prolonged in duration.

Before attacks of migraine both with and without aura, a prodrome of behavioral changes may occur, which may include depression, anxiety, elation, increased sensitivity to external stimuli, and increased or decreased libido. In many instances, the characteristics of a person's prodrome are stereotypical, producing similar changes before each attack. Associated symptoms of both types of migraine include nausea, vomiting, photophobia, and phonophobia. In the 24 hours after the attack subsides, a spectrum of behavioral changes may arise, ranging from depression to exhilaration.

Migraine attacks both with and without aura may have characteristic triggers, including certain foods (e.g., chocolate, blue cheese, and alcohol), erratic mealtimes, sleep loss, acute stress, exercise, atmospheric pressure change, and the use of certain drugs, such as nitroglycerin and oral contraceptives. Menstruation is a common trigger. When migraine occurs only at the time of menses, it is termed menstrual migraine. Such patients may also suffer ovulatory migraine, and they are more likely to have experienced their first migraine in the year of menarche and to cease having attacks during pregnancy. Menopause is often a time of severe and frequent migraine attacks, which later resolve. It is helpful in the management of the disorder to distinguish between triggers that are time-locked to a single attack and triggers that increase the frequency and severity of attacks. As an example of the latter, use of oral contraceptives may precipitate migraine for the first time, increase the frequency of attacks, and even convert migraine without aura to migraine with aura.

Hemiplegic migraine Transient hemiparesis associated with a migraine attack was first described by Liveing in 1873. In 1910, Clarke published the first report of hemiplegic migraine occurring in a family. Hemiplegic migraine also has been described in children. The IHS classifies hemiplegic migraine under migraine with typical aura or migraine with prolonged aura. Familial hemiplegic migraine is also classified as a subgroup of migraine with aura; the working definition includes the criteria for migraine with aura with hemiplegic features that may be prolonged, along with at least one first-degree relative having identical attacks.

Attacks are characterized by episodic hemiparesis or hemiplegia. In most attacks, the arm and leg are involved, often combined with face and hand paresis. Isolated facial and arm paresis occurs less often. The progression of the motor deficit is slow, with a spreading or marching quality. In most cases, symptoms are accompanied by homolateral sensory disturbance, particularly of hand and lower-face distribution, also with a slowly spreading or marching quality. Infrequently, the hemiparesis may alternate from side to side, even during an attack. Myoclonic jerks have been reported but are rare. Visual disturbance taking the form of hemianopic loss or typical visual aura is common, but homolateral or contralateral localization of the visual disturbance is uncertain. When dysphasia occurs, it is more often expressive than receptive. The neurologic symptoms last 30 to 60 minutes and are followed by severe pulsating headache that affects one side or both sides of the head. Nausea, vomiting, photophobia, and phonophobia are associated features. In severe cases, the aura persists throughout the headache phase. Uncommon manifestations of severe hemiplegic migraine attacks include fever, drowsiness, confusion, and coma, all of which may be prolonged (i.e., from days to weeks).

Familial hemiplegic migraine, which has an autosomal dominant inheritance pattern, is characterized by the same neurologic features as the nonfamilial form, with identical features occurring in at least one other first-degree relative. Additional neurologic deficits described with the disorder include a syndrome of progressive cerebellar disturbance, dysarthria, nystagmus, and ataxia. Retinitis pigmentosa, sensory neural deafness, tremor, dizziness, and oculomotor disturbances with nystagmus have also been described. These neurologic deficits are present between attacks and are not part of the aura.

The complications of hemiplegic migraine, though rare, can be serious. True migraine-induced stroke occurs when a typical migraine aura with hemiparesis persists after the attack; imaging studies of the brain show cerebral infarction appropriate to the neurologic deficit. In rare instances, severe hemiplegic migraine leads to persistent minor neurologic disorders; the cumulative effects of repeated attacks may produce profound multifocal neurologic damage or even dementia.

Familial hemiplegic migraine has been recently mapped to chromosome 19. The most likely location for the gene is a 30 cM interval between microsatellite markers D19S216 and D19S215, which also encompasses the probable position of a disease termed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoen cephalopathy, or CADASIL.

Basilar migraine The concept of basilar artery migraine was first proposed in 1961 by Bickerstaff, whose attention was drawn to the syndrome when he saw, within a short period of time, two patients with identical symptoms explicable only on the basis of an abnormality of basilar artery circulation. One patient was a boy 14 years of age whose symptoms lasted a few hours and were repeated on numerous occasions. The other patient was an elderly man whose symptoms progressed rapidly to coma and death; autopsy revealed infarction of the brain stem and occipital cortex caused by thrombotic occlusion of the basilar artery. Thus, it was by clinical analogy between the structural lesion in the basilar artery and the symptoms of basilar artery territory ischemia that basilar artery migraine was first described.

Basilar migraine is an episodic disorder. Over one third of patients experience the first attack in their second decade, whereas about two thirds experience the first attack in their second or third decade. The condition occurs frequently in children. However, a small number of cases appear for the first time in patients older than 50 years. The condition may occur in combination with other forms of migraine, though basilar migraine remains dominant. Bickerstaff initially noted a predominance of teenage girls in his basilar artery migraine population, but subsequent experience revealed that in females, the incidence of basilar migraine was similar to that of other forms of migraine. Sometimes, when basilar artery migraine starts in the teenage years, the frequency of the attacks diminishes with age and the syndrome is replaced in the adult years by other forms of migraine.

In most cases, the aura lasts five to 60 minutes, but it can last up to three days. Visual symptoms commonly occur first, predominantly in the temporal and nasal fields of vision. Visual disturbances may consist of blurred vision, teichopsia, scintillating scotoma, graying of vision, or total loss of vision. These features may start in one visual field and then become bilateral. When vision is not completely obscured, diplopia may occur, usually as a sixth nerve weakness.

Vertigo and gait ataxia are the next most common symptoms. The ataxia can be independent of vertigo. Tinnitus may accompany vertigo. Dysarthria is as common as ataxia and vertigo. Tingling and numbness, in a typical hand and lower-face spreading pattern (as seen in migraine with aura), are usually bilateral and symmetric but may alternate sides in a hemidistribution. Occasionally, dysesthesias extend to the trunk. Bilateral motor weakness occurs in over 50 percent of cases.

Impairment of consciousness in some form is common, often resembling sleep from which patients can be easily aroused by stimulation, only to return to the same state. In rare instances, this impaired consciousness progresses to stupor and then prolonged coma. Other forms of altered consciousness include amnesia and syncope. Drop attacks with very transient loss of consciousness may occur as part of the full clinical syndrome but are rare.

Headache occurs in almost all patients. In most, it has an occipital location; has a throbbing, pounding quality; and is accompanied by severe nausea and vomiting. It is unusual for the headache to be unilateral or localized to the more anterior parts of the cranium. Photophobia and phonophobia occur in one third to one half of patients.

There is an association between recurrent vertigo and basilar migraine. The vertigo usually starts in preschoolers and progresses into the teens. Abrupt attacks of rotational sensation occur, lasting seconds to minutes, accompanied by loss of balance, pallor, and vomiting. The disorder is self-limiting but may be a precursor to migraine or a migraine equivalent, because many sufferers subsequently develop migraine with or without aura.

Seizures have been observed in association with basilar migraine, and electroencephalographic changes without seizures may occur with attacks of typical basilar artery migraine.²³ These cases may have a good response to anticonvulsant agents. The EEG findings between attacks are usually spike and slow-wave complexes. During an attack, there are diffuse high-voltage slow waves and associated spikes with sharp waves and diffuse beta activity. It is controversial whether the association between seizures and basilar migraine is primarily one of a migraine syndrome with secondary epileptic features resulting from functional change caused by repeated migraine auras or one of a primarily basilar migraine attack that evokes epileptogenic features on the EEG and clinical seizures.

Ophthalmoplegic migraine An attack of migraine headache can be accompanied by third, fourth, or sixth cranial nerve paresis ipsilateral to the side of the headache, beginning either as an aura or during the headache phase. In most cases, the ocular palsy involves the third nerve; the sixth and fourth nerves are involved only in rare instances. The ophthalmoplegia is at first transient, but after repeated episodes, it can become permanent. The mechanisms involved in the production of ophthalmoplegic migraine remain speculative. The major differential diagnosis is aneurysmal dilatation of the cerebral arteries-particularly the internal carotid artery or the posterior communicating artery. As a strict rule, all cases should be promptly evaluated. The diagnosis of ophthalmoplegic migraine has become an even greater rarity since brain imaging has become available, which suggests that many earlier cases were misdiagnosed.

Retinal migraine Retinal migraine occurs more frequently than ophthalmoplegic migraine (i.e., approximately one in 200 migraine sufferers). However, persons who experience homonymous field defects are often diagnosed with monocular migraine because the temporal hemifields of vision are larger than the nasal hemifields. The term anterior visual pathway migraine is actually preferred, because the disorder is not limited to the retina. Typically, visual disturbances identical to migraine with aura occur in a monocular distribution, which may include complete monocular visual loss. There is often a previous history of migraine with or without aura. Headache may or may not follow. Episodes can be precipitated by postural change or exercise.

The mechanism of anterior visual pathway migraine is uncertain, but retinal vasospasm has been observed in certain cases. Although permanent visual field loss is unusual, persons who experience frequent episodes of anterior visual pathway migraine should probably receive prophylactic therapy. The diagnosis of this disorder should be one of exclusion because the condition is relatively rare, and monocular visual loss can be a presenting syndrome of serious vascular or other structural disease.

Stroke The coincidence of migraine and stroke is one of the most intriguing and perplexing problems for the diagnostician. Early epidemiological studies that addressed an association between migraine and stroke defined the relative risk of thrombotic stroke as nearly two times greater for women with migraine, but the significance of these studies is difficult to judge. More recently, in a rigorous case-control study, there was no overall association between migraine and ischemic stroke. However, women younger than 45 years with migraine were shown to have a four times greater risk of stroke than women without migraine; the risk was further increased in women with migraine who smoked.

When the study was extended to a larger population, the results were confirmed and strengthened. In this extended study, the risk of stroke in women younger than 45 years was three times greater for women with migraine without aura and six times greater for women with migraine with aura, compared with control subjects. In young women with migraine who smoked, the stroke risk was approximately 10 times greater than that of young nonsmoking women without migraine and more than three times greater than that of young women without migraine who smoked. For young women with migraine taking oral contraceptives, the risk of stroke was 14 times greater than that of control subjects and four times greater than that of young women taking oral contraceptives who did not suffer from migraine. There was a dose-effect relation between risk of stroke and the dose of estrogen: the odds ratio was 4.8:1 for pills with 50 mg of estrogen, 2.7:1 for pills with 30 to 40 mg of estrogen, 1.7:1 for pills with 20 mg of estrogen, and 1:1 for progestogen. In none of these cases was the stroke induced by a migraine attack. Although these risk figures are startlingly high compared with those of control subjects, it must be remembered that the absolute risk of stroke for young women with migraine translates to around 19 per 100,000 per year, which is a low stroke risk. Nevertheless, these data provide another compelling argument against smoking and dictate a review of contraceptive methods for young women with migraine.

Epilepsy The reported frequency of migraine among patients with epilepsy varies from 8.4 to 23 percent. The frequency of epilepsy among patients with migraine ranges from one to 17 percent. Such data suggest that there is no conclusive evidence of any relation between the two disorders other than random coincidence. Nevertheless, in a recent study, three percent of a cohort of adult patients with epilepsy experienced seizures during or immediately after migraine. Furthermore, the genetic relation between migraine and epilepsy (which has always been controversial) was clarified in a 1993 study by Ottman, Hong, and Lipton, who collected data on the prevalence of migraine in patients with epilepsy and in relatives with and without epilepsy. Of the probands, 24 percent had a migraine history; 26 percent of relatives with epilepsy had a migraine history. However, 15 percent of relatives who did not have epilepsy had a migraine history. The cumulative incidence of migraine was also higher in patients with epilepsy (24 percent) and relatives with epilepsy (23 percent), compared with relatives without epilepsy; and the risk of migraine for the first two groups was twice as high as that for the third group. There also appears to be a high incidence of migraine in persons with certain forms of epilepsy, such as benign rolandic epilepsy, benign occipital epilepsy, and corticoreticular epilepsy with absence.

Psychiatric disorders and personality traits There is a high incidence of neuroticism in migraine sufferers. However, the stereotype of the rigid, obsessive migraine personality could well be a selection bias of a migraine subtype seen more frequently in the clinical population. A few studies have been made of migraine and psychiatric disorders. Recent epidemiological studies have shown a major comorbidity with depression. Although this association with depression may represent a psychological reaction to frequent and disabling migraine attacks, depression carries with it a major risk for migraine, raising the possibility that there is a shared genetic or environmental risk between the disorders. A common abnormality of brain function may be responsible-for example, dysregulation of the central serotoninergic system. Increased risk for episodes of mania, anxiety, and panic disorder have also been reported, together with an increased prevalence of illicit drug use and nicotine dependence. Perhaps the most disturbing feature of this report was the increased lifetime prevalence of suicidal ideation and suicide attempts independent of depression.

The goals of migraine treatment are alleviation of the symptoms of an acute attack and prevention of further attacks, either by behavioral or pharmacological means. The behavioral approach commonly involves regular sleep and meals and avoidance of initiating factors. Family-related or work-related stresses and emotional problems are often unavoidable and are best managed by stress-coping or relaxation techniques. Pharmacological treatments for migraine are available .

Analgesic drugs During prolonged, severe attacks of migraine, the patient's judgment may be impaired, with consequent uncertainties as to the type of drug to be used or the amount to be taken. Family or friends should be instructed in the use of medications for acute cases of migraine. Mild or moderate attacks should be treated with simple analgesic drugs or nonsteroidal anti-inflammatory drugs (NSAIDs).

Aspirin, acetaminophen, propoxyphene, codeine, and certain NSAIDs are all superior to placebo in relieving the pain of migraine. Effervescent formulations are more effective because they are absorbed more rapidly. Because gastric stasis often accompanies migraine attacks, metoclopramide, a drug that increases gut motility and promotes gastric emptying, enhances the effectiveness of analgesic drugs. However, metoclopramide should be used sparingly in adults and should not be used at all in young patients, because it can cause dystonia. When nausea and vomiting are prominent, suppository preparations of analgesic and antiemetic drugs can be given. The most frequently used antiemetic drugs are perphenazine, prochlor perazine, and chlorpromazine.

Ergot preparations For many years, ergotamine tartrate was the drug of choice for treatment of moderate to severe acute migraine attacks. However, controlled trials have proved that ergotamine is effective in only half of patients when given orally, sublingually, rectally, or nasally. The addition of caffeine enhances the absorption and possibly the vasoconstrictive activity of ergotamine. Because absorption of ergotamine and related drugs is variable, the drug should be given by a route acceptable to the patient, and the dosages should be increased to find a single, effective dose as early as possible for subsequent attacks. Ergotamine is best absorbed rectally. An antiemetic drug (best given by suppository) may be needed together with ergotamine. Dihydroergotamine, which is available for parenteral administration in the United States, is also effective in migraine attacks. Patients can be instructed to self-administer dihydroergotamine subcutaneously. Ergot preparations are vasoconstrictors and should not be given to patients with vascular disease.

Sumatriptan Sumatriptan is a serotonin receptor agonist that recently was proved to be effective in migraine. Sumatriptan is effective when administered subcutane ously during an attack of migraine. Subcutaneous administration of 6 mg of sumatriptan reduces migraine within two hours in up to 86 percent of patients. Nausea and vomiting are effectively relieved in most patients. Unfortunately, headache can recur in up to 46 percent of patients within 24 hours, probably because of the short half-life of the drug.

When sumatriptan is given orally in a dose of up to 100 mg, headache and associated symptoms are relieved within four hours in 75 percent of patients. The usual dose is 25 mg. As with subcutaneous administration, headache recurrence is a problem.

The side effects of subcutaneous and oral sumatriptan are similar. Most of the side effects are mild to moderate in intensity, are short-lived, resolve spontaneously, and do not change with repeated use of sumatriptan. The most common side effects are injection-site reaction after subcutaneous administration; sensations of flushing, heat, and tingling; and neck pain with stiffness. Three to five percent of patients experience chest tightness, heaviness, pressure, tingling, and pain. The cause of the chest symptoms is unknown, but in rare instances, coronary vasospasm has undoubtedly occurred. For patients who are likely to have unrecognized coronary artery disease (e.g., postmeno pausal women, men older than 40 years, and patients with risk factors for coronary artery disease), the first dose of sumatriptan should be given under medical supervision. Sumatriptan is contraindicated in patients with a history of myocardial infarction, symptomatic ischemic heart disease, Prinzmetal's angina, and hypertension.

Symptomatic treatment in the emergency department Migraine attacks that are severe, prolonged, and unresponsive to self-administered medication may be treated in the clinic or emergency department. Patients with such attacks should be treated with dihydroergotamine given intravenously or intramuscularly or with sumatriptan given subcutaneously. If these drugs fail, the preferred regimens are metoclopramide (10 mg I.V.), prochlorperazine (10 mg I.V.), or chlorpromazine administered in three intravenous injections of 0.1 mg/kg given 15 minutes apart. In addition to dystonia and tardive dyskinesia, the side effects of the three drugs are drowsiness, nausea, vomiting, dizziness, and hypotension, all of which are infrequent. The mechanism by which these dopamine antagonists relieve headache remains to be determined.

Major narcotic analgesic drugs-particularly meperidine-are used in the emergency treatment of migraine attacks. The use of meperidine should be limited to patients who have attacks that do not respond to antimigraine preparations and patients in whom antimigraine drugs are contraindicated (e.g., those with peripheral vascular or coronary artery disease and pregnant women).

Acute attacks may be so frequent and the patient's pain so severe and continuous that hospitalization is needed. In these patients, it may be effective to administer dihydroergotamine intravenously for three to four days, discontinue all other drugs, and administer intravenous fluids.

Preventive treatment should be considered only when attacks of migraine occur more than two or three times a month, when the attacks are severe and limit normal activity, when the patient is unable to cope with the attacks, when symptomatic therapies have failed or have had serious side effects, and when attempts at nonpharmacological prevention have failed. Several points should be considered before preventive therapy is initiated. Some form of contraception-preferably barrier contraception rather than an oral contraceptive (which may trigger headache)-should be advised in women of childbearing age. Costs of drugs should always be considered because prolonged treatment may be required.

Each medication should be given for a period adequate enough for its effectiveness to be determined. In patients with frequent migraine, this is usually two to three months. Preventive treatment is usually continued for six months or longer and gradually withdrawn after the frequency of headaches diminishes. Serotonin-influencing drugs were the first to be used effectively for migraine prevention . Methysergide is more effective than amitriptyline but it is not used much because it can cause retro peritoneal, cardiac valvular, and pleural fibrosis. Methysergide is contraindicated in patients with vascular disease because of its vasoconstricting action. Amitriptyline is a very useful drug for preventing migraine, especially in patients with depression or tension-type headaches, though its beneficial effect in migraine is independent of its antidepressant activity.

Beta₂-adrenergic antagonist drugs have proved effective in preventing migraine in numerous clinical trials. They should be considered the treatment of choice for preventing migraine, especially in patients with stress-related attacks. However, these drugs are effective in only up to 65 percent of treated patients and are contraindicated in patients with bronchospasm, congestive heart failure, cardiac arrhythmias, and a history of depression. Beta₂-receptor antagonists with partial agonist activity are ineffective.

Despite initial enthusiasm for the use of calcium channel blocking agents to prevent migraine, their impact has been unimpressive. Verapamil is probably used the most. In general, the calcium channel blockers may decrease the frequency of attacks, but they have little effect on their severity. It may take weeks to months before an effect is noted, which reduces patient compliance. The vasodilatory action of calcium channel blockers sometimes causes severe headache that is indistinguishable from migraine.

NSAIDs have been used in satisfactorily controlled trials . Aspirin is also effective in preventing migraine. However, because of gastrointestinal ulceration and hemorrhage, prolonged prophylaxis with NSAIDs should be avoided. No comparison has been made of the relative effectiveness of the various classes of NSAIDs, but it is reasonable to change to another class if one has proved ineffective.

Valproic acid was recently introduced as preventive therapy for migraine, but it is only moderately effective in preventing migraine and reducing the frequency, severity, and duration of severe attacks. The mechanism of action of valproic acid is not known.

Menstrual migraine (i.e., an attack occurring only in association with menses) is frequently refractory to treatment. Women with menstrual migraine may benefit from preventive treatment limited to the period of menses. If they are already receiving prophylactic treatment, an increased dose at time of menses may be beneficial. The use of percutaneous estradiol gel applied just before and throughout menses may reduce the frequency of headache. Patients already taking oral contraceptives who continue taking them throughout the menstrual cycle may experience fewer attacks.

The mechanisms by which ovarian hormones influence migraine remain to be determined, but an abrupt fall in serum estrogen concentrations before the onset of an attack appears to be a critical factor. The currently used low-dose estrogen oral contraceptive formulations are associated with a haphazard occurrence of attacks during the cycle, probably because of fluctuating serum estrogen concentrations. Thus, treatment strategies are aimed at preventing either a fall or a substantial fluctuation in serum estrogen levels. Women already taking estrogen who have frequent migraine attacks may improve if the hormone is either stopped or increased.

Cluster headache is a disorder that occurs six times more often in men than in women, usually beginning in the third or fourth decade of life. Attacks occur during defined periods that may last weeks to months and may return within a span of one or more years. Not infrequently, the cluster periods resume according to well-defined cycles that may be associated with seasons. As time passes, the cluster periods become longer and merge into one another as the duration of remission shortens, so that subjects enter a stage termed chronic cluster headache-clearly a misnomer. When headaches occur in a cluster, there are usually several clear-cut triggers of an attack (the most common being alcohol and nitro glycerin), all of which appear to have vasodilator properties.

The causes of cluster headache remain to be determined. Paresis of the sympathetic nerve fibers that traverse the cavernous sinus to innervate orbital and retro-orbital structures appears to play an important role. Indeed, after severe and frequent attacks, persons may be left with permanent sympathetic palsy. In addition, the trigeminal system must transmit the pain, which probably originates in dilated and sensitized arteries and veins. A relapsing and remitting venous inflammatory process of unknown cause has been suggested as the underlying basis of cluster headache.

Cluster headache attacks are characteristically unilateral and periocular, though they may also occur in frontal, temporal, or maxillary locations. The pain is almost always excruciating and is usually described as boring, knifelike, or burning. The pain is accompanied by conjunctival injection, lacrimation, rhinorrhea, and miosis. The attacks are relatively short, lasting from 15 minutes to three hours. They may recur numerous times during the day but usually only two or three times. Cluster headache attacks often wake the patient during the night. These clinical features of cluster headache are so stereotypical that the diagnosis can be made on their basis alone without resorting to other investigations.

Cluster headache sufferers do not search for a quiet environment to relax. They tend to pace the floor and bang their heads against hard surfaces, hoping to relieve the excruciating pain. In rare instances, patients with cluster headache are photophobic, phonophobic, or both and require a dark room to alleviate the pain.

One hundred percent oxygen is effective in about 70 percent of patients when it is delivered in a tight-fitting face mask at 7 L/min for 10 minutes. Ergotamine nasal spray may provide rapid benefit.

Dihydroergotamine given subcutaneously is also effective. Two percent lidocaine intranasal drops (or occasionally lidocaine gel) is sometimes beneficial in acute cluster attacks. The patient's head should be kept back and tilted toward the side of the headache when the lidocaine anesthetic is applied. Subcutaneous administration of sumatriptan is very effective in treatment of acute episodes of cluster headache. Sumatriptan has a rapid onset of action, making it ideal for the treatment of severe cluster headaches of short duration. If treatment fails or medications are contraindicated, acute intravenous glucocorticoids or intramuscular meperidine may be indicated. Finally, hospital admission and the use of intravenous dihydroergotamine may be indicated in intractable cases.

Prevention of attacks during the cluster period is almost always indicated because of the severity of pain. Preventive treatment is probably best achieved by a short course of glucocorticoids (e.g., prednisone, 60 mg/day), usually for two weeks and then tapered over 10 days. However, this strategy cannot be repeated regularly. Verapamil (up to 80 mg four times a day) or lithium carbonate (300 mg three times a day) can be given. Alternatively, 0.5 to 1 mg of ergotamine may be given in suppository form at night and may be very effective. There is no published experience of the use of sumatriptan as a preventive treatment of cluster headache. Although it may have a similar action to ergotamine, it has a much shorter half-life and may have less utility for this purpose.

Chronic paroxysmal hemicrania is a primary headache so rare that it will probably never be diagnosed in a nonspecialist setting, but it demands mention because it resembles aspects of cluster headache. The pain is similar in intensity and location to cluster headache, but the attacks are short (rarely longer than 30 minutes) and very frequent (up to 30 times a day). The disorder is also distinct from cluster headache because it rarely occurs in men and is entirely resolved by use of indomethacin. The condition also needs to be differentiated from other rare headache forms that occur around the eye, such as the cluster-tic syndrome and the SUNCT syndrome (short-lasting, unilateral, neuralgiform headache with conjunctival injection and tearing). Hemicrania continua, a controversial primary headache, is also selectively responsive to indomethacin.

Tension-type headache is typically pressing or tightening in quality, mild to moderate in intensity, and bilateral in location and does not worsen with physical activity. Phonophobia, photophobia, or both are occasionally present, but nausea is absent. An attack may last hours to days. If tension-type headache occurs more than 15 days a month for six months, the condition is termed chronic as opposed to episodic tension-type headache. Whereas almost 60 percent of the population may suffer episodic ten sion-type headache in any one year, the chronic form is present in fewer than three percent.

The mechanisms of tension-type headache remain to be determined. The previous term for this disorder, tension headache, was coined because the pericranial and pericervical muscles were thought to be involved (i.e., muscle contraction headache). Indeed, this may still be the cause in some cases. Recent neurophysiological studies have found an abnormality of a temporalis muscle reflex that indicates a brain stem origin of disinhibited muscle contraction.

Episodic tension-type headache can pose a problem in differential diagnosis. Some authorities consider that the distinction between episodic tension-type headache and migraine without aura is unwarranted, whereas others disagree. The distinction is even more difficult in the context of the so-called mixed headaches, in which attacks of migraine with aura occur against a background of chronic tension-type headache. Contemporary headache specialists call this chronic daily headache, with the hallmark of the condition being its development over time (maturational migraine) from an earlier and unequivocal diagnosis of episodic migraine. So-called chronic daily headache, as yet unrecognized in the IHS classification, is compounded by the frequent use of analgesic and sedative medications, which some experts consider to be instigators of the condition.

An exacerbation of episodic tension-type headache is best treated by bed rest and complete relaxation. Precipitating factors should be sought, and reassurance and psychological support should be provided for the patient. Gentle massage of the head and neck area and application of hot packs to these areas are physical maneuvers that may be helpful in alleviating some of the pain. In view of the risk of analgesic addiction in patients with chronic headache, only minor analgesics should be used. If the patient has consistently used scheduled analgesics, such as codeine, the pain of an acute exacerbation of severe muscle contraction headache may not respond to anything but parenteral narcotics. Accordingly, instead of pursuing this line of treatment, it is preferable to treat the patient with tranquilizers that are also neuromuscular relaxants, such as diazepam, which may have the added beneficial effect of causing drowsiness and sleep. Muscle relaxants are occasionally effective in acute exacerbations. NSAIDs, such as naproxen and ibuprofen, are useful alternative analgesics that are effective in some patients.

For the management of chronic tension-type headache, a similar pain strategy is employed. In this instance, it is better to avoid tranquilizers and to try preventive measures with pharmacotherapy but only if behavioral measures, such as regular sleep and effective stress-coping, have failed. The tricyclic antidepressants, such as amitriptyline, are the most effective preventive drugs.

Conversion headache is one of the most difficult forms of headache to diagnose; indeed, a long delay in diagnosis is almost a diagnostic feature. Most cases have an abrupt onset followed by exacerbations and remission. The incidence in men and that in women are nearly identical. Conversion headache occurs predominantly in adults 18 to 30 years of age, but it can be observed at all ages. The character of conversion headache often cannot be differentiated from that of other types of headache. In addition, major abnormalities in mental status are seldom found in patients with conversion reaction. Laboratory, electrophysiological, and radiologic studies are normal. The usual duration is from months to years, but in most cases, diagnosis is made within one year of initial presentation. Conversion headache is rarely relieved by medication.

On examination, the major abnormalities are behavioral in nature. Patients may have a total indifference to their symptomatology despite bitter complaints of pain. In addition, symptoms may be overdramatized, particularly when they are of an unusual description. Patients may exhibit extreme passivity or express hostile denials when they are asked about possible emotional problems. The psychiatric examination rarely reveals serious psychiatric disease, but the personality profile may indicate that the patient is an immature, dependent person.

The IHS has classified miscellaneous headaches under primary headaches even though less is known about the mechanisms of miscellaneous headaches than about the other primary headache syndromes. Notable characteristics of the miscellaneous headaches include a resemblance of the head pain to that of serious structural disorders; thus, miscellaneous headaches require special mention and often good clinical judgment as to the extent into which they are investigated.

Idiopathic stabbing pain includes the syndromes of so-called ice-pick headache and so-called jabs and jolts. Transient stabs or series of stabs of head pain lasting fractions of a second occur at irregular intervals of hours to days. Patients with migraine, cluster headache, and chronic paroxysmal hemicrania are predisposed to this condition . An important differential diagnosis is the sentinel headache of subarachnoid hemorrhage, which most often can be discriminated from idiopathic stabbing pains by a history of past events in the case of subarachnoid hemorrhage.

External compression headache is a constant pain resulting from external pressure applied to the site from which it originates, usually by stimuli such as swim goggles. The pain is mediated by the trigeminal or occipital nerves.

As the name implies, cold stimulus headache results from exposure of the head to low temperatures. This includes a generalized headache from exposure of the bare head to subzero weather or from diving into cold water. Ingestion of a cold stimulus, best typified by ice-cream headache, produces a more focused and more severe pain, usually frontal or retropharyngeal in location.

Benign cough headache is a bilateral headache of sudden onset lasting less than a minute that is precipitated by coughing. It can be diagnosed only after structural lesions, especially posterior fossa space-occupying lesions, have been excluded.

In contrast to the benign cough headache, benign exertional headache is brought on by physical effort, lasts minutes, and has a throbbing, pounding quality. It too has the important differential diagnosis of intracranial mass.

Headache associated with sexual activity, which is often known as benign coital cephalalgia, can take three forms. In one form, the headache has a sudden onset precisely at the time of orgasm. In another form, the headache can begin gradually during sexual excitement and then intensify at the time of orgasm. The headache of sudden onset is explosive in chararacter, and the headache of gradual onset is a dull ache. In both headaches, but more commonly in the one of sudden onset, the headache occurs at the time of masturbation, a historical feature that may be helpful in distinguishing it from subarachnoid hemorrhage. Curiously, these headaches may occur with a clusterlike periodicity. The third type of headache associated with sexual activity is postural headache, resembling intracranial hypotension. Unlike the other types, which are short-lived, the postural headache may persist for days. The mechanisms of these headaches remain to be determined. The conditions usually spontaneously remit; however, if preventive management is desired, propranolol may be tried. Propranolol has been successful in some cases, perhaps by preventing an increase in blood pressure at orgasm.