HEADACHE, INCLUDING MIGRAINE 1

HEADACHE, INCLUDING MIGRAINE AND CLUSTER HEADACHE

Few of us are spared the experience of head pain. As many as 90% of individuals have at least one headache per year. Severe, disabling headache is reported to occur at least annually by 40% of individuals worldwide. A useful classification of the many causes of headache is shown in . Headache is usually a benign symptom, but occasionally it is the manifestation of a serious illness such as brain tumor, subarachnoid hemorrhage, meningitis, or giant cell arteritis. In emergency settings, approximately 5% of patients with headache are found to have a serious underlying neurologic disorder. Therefore, it is imperative that the serious causes of headache be diagnosed rapidly and accurately.

PAIN-SENSITIVE STRUCTURES OF THE HEAD

Pain is most commonly due to tissue injury resulting in stimulation of peripheral nociceptors in an intact nervous system. Pain can also result from damage to or anomalous activation of pain-sensitive pathways of the peripheral or central nervous system. Headache may originate from either or both mechanisms. Relatively few cranial structures are pain-sensitive: the scalp, middle meningeal artery, dural sinuses, falx cerebri, and the proximal segments of the large pial arteries. The ventricular ependyma, choroid plexus, pial veins, and much of the brain parenchyma are pain-insensitive. Electrical stimulation of the midbrain in the region of the dorsal raphe has resulted in migraine-like headaches. Thus, whereas most of the brain is insensitive to electrode probing, a site in the midbrain represents a possible source of headache generation. Sensory stimuli from the head are conveyed to the central nervous system via the trigeminal nerves for structures above the tentorium in the anterior and middle fossae of the skull and via the first three cervical nerves for those in the posterior fossa and the inferior surface of the tentorium.

Headache can occur as the result of (1) distention, traction, or dilation of intracranial or extracranial arteries; (2) traction or displacement of large intracranial veins or their dural envelope; (3) compression, traction, or inflammation of cranial and spinal nerves; (4) spasm, inflammation, or trauma to cranial and cervical muscles; (5) meningeal irritation and raised intracranial pressure; or (6) other possible mechanisms such as activation of brainstem structures.

GENERAL CLINICAL CONSIDERATIONS

The quality, location, duration, and time course of the headache and the conditions that produce, exacerbate, or relieve it should be carefully reviewed. Ascertaining the quality of cephalic pain is occasionally helpful for diagnosis. Most tension-type headaches are described as tight "bandlike" pain or as dull, deeply located, and aching pain. Jabbing, brief, sharp cephalic pain, often occurring multifocally (ice pick-like pain), is the signature of a benign, nondescript disorder. A throbbing quality and tight muscles about the head, neck, and shoulder girdle are common nonspecific accompaniments of vascular headaches.

Pain intensity rarely has diagnostic value, although from the patient's perspective, it is the single aspect of pain that is most important. Although meningitis, subarachnoid hemorrhage, and cluster headache produce intense cranial pain, most patients entering emergency departments with the most severe headache of their lives usually have migraine. Contrary to common belief, the headache produced by a brain tumor is not usually distinctive or severe.

Data regarding location of headache may be informative. If the source is an extracranial structure, as in giant cell arteritis, the correspondence with the site of pain is fairly precise. Inflammation of an extracranial artery causes pain and exquisite tenderness localized to the site of the vessel. Lesions of paranasal sinuses, teeth, eyes, and upper cervical vertebrae induce less sharply localized pain, but pain that is still referred in a regional distribution. Intracranial lesions in the posterior fossa cause pain that is usually occipitonuchal, and supratentorial lesions most often induce frontotemporal pain.

Duration and time-intensity curves of headaches are diagnostically useful. A ruptured aneurysm results in head pain that peaks in an instant, thunderclap-like; much less often, unruptured aneurysms may signal their presence in the same way. Cluster headache attacks reach their peak over 3 to 5 min, remain at maximal levels for about 45 min, and then taper off. Migraine attacks build up over hours, are maintained for several hours to days, and are characteristically relieved by sleep. Sleep disruption and early morning headaches that improve during the day are characteristics of headaches produced by brain tumors.

The analysis of facial pain requires a different approach. Trigeminal and, less commonly, glossopharyngeal neuralgia are frequent causes of facial pain . "Neuralgias" are painful disorders characterized by paroxysmal, fleeting, often electric shock-like episodes that are frequently caused by demyelinating lesions of nerves (the trigeminal or glossopharyngeal nerves in cranial neuralgias). Certain maneuvers characteristically trigger paroxysms of pain. However, the most common cause of facial pain by far is dental; provocation by hot, cold, or sweet foods is typical. The application of a cold stimulus will repeatedly induce dental pain, whereas in neuralgic disorders, a refractory period usually occurs after the initial response so that pain cannot be repeatedly induced.

The effect of eating on facial pain may provide insight into its cause. Is it the chewing, swallowing, or taste of the food that elicits pain? Chewing points toward trigeminal neuralgia, temporomandibular joint dysfunction, or giant cell arteritis ("jaw claudication"), whereas swallowing and taste provocation point toward glossopharyngeal neuralgia. Pain upon swallowing is common among patients with carotidynia (see below) because the inflamed, tender carotid artery abuts the esophagus during deglutition.

Many patients with facial pain do not experience stereotypic neuralgias; the term atypical facial pain has been used in this setting. Vague, poorly localized, continuous facial pain is characteristic of nasopharyngeal carcinoma; a burning pain often develops as deafferentation occurs and evidence of cranial neuropathy appears. Burning facial pain may also occur with tumors of the fifth cranial nerve (meningioma or schwannoma) or with lesions of the pons that interrupt the dorsal root entry zone of the nerve (multiple sclerosis). In patients with facial pain, the finding of objective sensory loss is an important clue to a serious underlying disorder. Occasionally, the cause of a pain problem cannot be resolved promptly, necessitating periodic follow- up until further signs appear.

CLINICAL EVALUATION OF ACUTE, NEW-ONSET HEADACHE

Patients who present with their first severe headache raise entirely different diagnostic possibilities than those with recurrent headaches over many years. In new-onset and severe headaches, the probability of finding a potentially serious cause is considerably greater than in recurrent headache. When a patient complains of an acute, new-onset headache, a number of causes should be considered including meningitis, subarachnoid hemorrhage, epidural or subdural hematoma, glaucoma, and purulent sinusitis. Clinical features of acute, new-onset headache caused by serious underlying conditions are summarized in .

A complete neurologic examination is an essential first step in the evaluation. In most cases, an abnormal examination should be followed by a computed tomography (CT) or a magnetic resonance imaging (MRI) study. As a screening procedure for intracranial pathology in this setting, CT and MRI methods appear to be equally sensitive. A general evaluation of acute headache might include the investigation of cardiovascular and renal status by blood pressure monitoring and urine examination; eyes by fundoscopy, intraocular pressure measurement, and refraction; cranial arteries by palpation; and cervical spine by the effect of passive movement of the head and imaging.

The psychological state of the patient should also be evaluated since a relationship exists between head pain and depression. Many patients in chronic daily pain cycles become depressed; moreover, there is a greater-than-chance coincidence of migraine with both bipolar (manic depressive) and unipolar major depressive disorders. Drugs with antidepressant actions are also effective in the prophylactic treatment of both tension-type headache and migraine.

Underlying recurrent headache disorders may be activated by pain that follows otologic or endodontic surgical procedures. Treatment of the headache problem is largely ineffective until the cause of the primary problem is addressed. Thus, pain about the head as the result of diseased tissue or trauma may reawaken an otherwise quiescent migrainous syndrome.

Serious underlying conditions that are associated with headache are described below and in.

MENINGITIS

In general, acute, severe headache with stiff neck and fever suggests meningitis. Lumbar puncture is mandatory. Often there is striking accentuation of pain with eye movement. Meningitis is particularly easy to mistake for migraine in that the cardinal symptoms of pounding headache, photophobia, nausea, and vomiting are present

INTRACRANIAL HEMORRHAGE

In general, acute, severe headache with stiff neck but without fever suggests subarachnoid hemorrhage. A ruptured aneurysm, arteriovenous malformation, or intraparenchymal hemorrhage may also present with only headache. Rarely, if the hemorrhage is small or below the foramen magnum, the head CT scan can be normal. Therefore, a lumbar puncture may be required to make the definitive diagnosis of a subarachnoid hemorrhage.

BRAIN TUMOR

Approximately 30% of patients with brain tumors consider headache to be their chief complaint. The head pain is usually nondescript¾an intermittent deep, dull aching of moderate intensity, which may worsen with exertion or change in position and may be associated with nausea and vomiting. This pattern of symptoms results from migraine far more often than from brain tumor. Headache of brain tumor disturbs sleep in about 10% of patients. Vomiting that precedes the appearance of headache by weeks is highly characteristic of posterior fossa brain tumors. A history of amenorrhea or galactorrhea should lead one to question whether a prolactin-secreting pituitary adenoma (or the polycystic ovary syndrome) is the source of headache. Headache arising de novo in a patient with known malignancy suggests either cerebral metastases and/or carcinomatous meningitis. Head pain appearing abruptly after bending, lifting, or coughing can be the clue to a posterior fossa mass (or a Chiari malformation).

TEMPORAL ARTERITIS

Temporal (giant cell) arteritis is an inflammatory disorder of arteries that frequently involves the extracranial carotid circulation. This is a common disorder of the elderly; its annual incidence is 77:100,000 in individuals aged 50 and older. The average age of onset is 70 years, and women account for 65% of cases. About half of patients with untreated temporal arteritis develop blindness due to involvement of the ophthalmic artery and its branches; indeed, the ischemic optic neuropathy induced by giant cell arteritis is the major cause of rapidly developing bilateral blindness in patients over 60 years of age. Because treatment with glucocorticoids is effective in preventing this complication, prompt recognition of this disorder is important.

Typical presenting symptoms include headache, polymyalgia rheumatica, jaw claudication, fever, and weight loss. Headache is the dominant symptom and often appears in association with malaise and muscle aches. Head pain may be unilateral or bilateral and is located temporally in 50% of patients but may involve any and all aspects of the cranium. Pain usually appears gradually over a few hours before peak intensity is reached; occasionally, it is explosive in onset. The quality of pain is only seldom throbbing; it is almost invariably described as dull and boring with superimposed episodic ice pick-like lancinating pains similar to the sharp pains that appear in migraine. Most patients can recognize that the origin of their head pain is superficial, external to the skull, rather than originating deep within the cranium (the pain site for migraineurs). Scalp tenderness is present, often to a marked degree; brushing the hair or resting the head on a pillow may be impossible because of pain. Headache is usually worse at night and is often aggravated by exposure to cold. Reddened, tender nodules or red streaking of the skin overlying the temporal arteries may be found in patients with headache, as is tenderness of the temporal or, less commonly, the occipital arteries.

The erythrocyte sedimentation rate (ESR) is often, though not always, elevated; a normal ESR does not exclude giant cell arteritis. A temporal artery biopsy and the initiation of prednisone at 80 mg daily for the first 4 to 6 weeks should be instituted when clinical suspicion is high. The prevalence of migraine among the elderly is substantial, considerably higher than that of giant cell arteritis. Migraineurs often report amelioration of their headaches with prednisone, so that one must be cautious about interpreting the therapeutic response.

GLAUCOMA

Glaucoma may present with a prostrating headache associated with nausea and vomiting. The history will usually reveal that the headache started with severe eye pain. On physical examination, the eye is often red with a fixed, moderately dilated pupil.

OTHER CAUSES OF HEADACHE

Systemic Illness There is hardly any illness that is never manifested by headache; however, some illnesses are frequently associated with headache. These include infectious mononucleosis, systemic lupus erythematosus, chronic pulmonary failure with hypercapnia (early morning headaches), Hashimoto's thyroiditis, inflammatory bowel disease, many of the illnesses associated with HIV, and the acute blood pressure elevations that occur in pheochromocytoma and in malignant hypertension. The last two examples are the exceptions to the generalization that hypertension per se is a very uncommon cause of headache; diastolic pressures of at least 120 mmHg are requisite for hypertension to cause headache. Persistent headache and fever are often the manifestations of an acute systemic viral infection; if the neck is supple in such a patient, lumbar puncture may be deferred. Some drugs and drug-withdrawal states, e.g., oral contraceptives, ovulation-promoting medications, and glucocorticoid withdrawal, are also associated with headache in some individuals.

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) Headache, clinically resembling that of brain tumor, is a common presenting symptom of pseudotumor cerebri, a disorder of raised intracranial pressure probably resulting from impaired cerebrospinal fluid CSF absorption by the arachnoid villi. Transient visual obscurations and papilledema with enlarged blind spots and loss of peripheral visual fields are additional manifestations. Most patients are young, female, and obese. They often have a history of exposure to provoking agents such as vitamin A and glucocorticoids.

Cough A male-dominated (4:1) syndrome, cough headache is characterized by transient, severe head pain upon coughing, bending, lifting, sneezing, or stooping. Head pain persists for seconds to a few minutes. Many patients date the origins of the syndrome to a lower respiratory infection accompanied by severe coughing or to strenuous weight-lifting programs. Headache is usually diffuse but is lateralized in about one-third of patients. The incidence of serious intracranial structural anomalies causing this condition is about 25%; the Chiari malformation is a common cause. Thus, MRI is indicated for most patients with cough headache. The benign disorder may persist for a few years; it responds dramatically to indomethacin at doses ranging from 50 to 200 mg daily. Approximately half of patients will also show a response to therapeutic lumbar puncture with removal of 40 mL of CSF.

Many patients with migraine note that attacks of headache may be provoked by sustained physical exertion, such as during the third mile of a 5-mile run. Such headaches build up over hours, in contrast to cough headache. The term effort migraine has been used for this syndrome to avoid the ambiguous term exertional headache.

Lumbar Puncture Headache following lumbar puncture usually begins within 48 h but may be delayed for up to 12 days. Its incidence is between 10 and 30%. Head pain is dramatically positional; it begins when the patient sits or stands upright; there is relief upon reclining or with abdominal compression. The longer the patient is upright, the longer the latency before head pain subsides. It is worsened by head shaking and jugular vein compression. The pain is usually a dull ache but may be throbbing; its location is occipitofrontal. Nausea and stiff neck often accompany headache, and occasional patients report blurred vision, photophobia, tinnitus, and vertigo. The symptoms resolve over a few days but may on occasion persist for weeks to months.

Loss of CSF volume decreases the brain's supportive cushion, so that when a patient is upright there is probably dilation and tension placed on the brain's anchoring structures, the pain-sensitive dural sinuses, resulting in pain. Intracranial hypotension often occurs, but severe lumbar puncture headache may be present even in patients who have normal CSF pressure.

Treatment with intravenous caffeine sodium benzoate given over a few minutes as a 500-mg dose will promptly terminate headache in 75% of patients; a second dose given in 1 h brings the total success rate to 85%. An epidural blood patch accomplished by injection of 15 mL of autologous whole blood rarely fails for those who do not respond to caffeine. The mechanism for these treatment effects is not straightforward. The blood patch has an immediate effect, making it unlikely that sealing off a dural hole with blood clot is its mechanism of action.

Postconcussion Following seemingly trivial head injuries and particularly after rear-end motor vehicle collisions, many patients report varying combinations of headache, dizziness, vertigo, and impaired memory. Anxiety, irritability and difficulty with concentration are other hallmarks of this syndrome. Symptoms may remit after several weeks or persist for months and even years after the injury. Postconcussion headaches may occur whether or not a person was rendered unconscious by head trauma. Typically, the neurologic examination is normal with the exception of the behavioral abnormalities, and CT or MRI studies are unrevealing. Chronic subdural hematoma may on occasion mimic this disorder. Although the cause of postconcussive headache disorder is not known, it should not in general be viewed as a primary psychological disturbance. It often persists long after the settlement of pending lawsuits. The treatment is symptomatic support. Repeated encouragement that the syndrome eventually remits is important.

Coital Headache This is another male-dominated (4:1) syndrome. Attacks occur periorgasmically, are very abrupt in onset, and subside in a few minutes if coitus is interrupted. These are nearly always benign events and usually occur sporadically; if they persist for hours or are accompanied by vomiting, subarachnoid hemorrhage must be excluded .