Chapter 205 – Headache and Facial Pain
JOEL M. WEINSTEIN
• Chronic, intermittent, or episodic pain that involves the head, skull, scalp, or face.
• Most headaches fall into specific rubrics (e.g., tension headache, migraine) that involve fairly common patterns of symptoms, such as a tightening band around the head in the late afternoon.
• Most headaches do not reflect serious organic disease.
• Though usually benign, the pain from headaches can be devastating and interfere with routine activities.
Headache and facial pain are among the most common complaints seen in medical practice. From the perspective of the ophthalmologist, the critical tasks are to:
• Diagnose correctly and treat painful intraocular and orbital disorders.
• Recognize various benign syndromes that cause headache and facial pain, including migraines, tension headaches, and cluster headaches.
• Identify the minority of patients who have headache caused by serious intracranial or systemic pathology.
In this chapter a working plan is developed to facilitate the diagnosis of patients in the last two categories. This requires both a knowledge of various nonophthalmological disorders and a new methodology with which to elicit the relevant clinical history.
EPIDEMIOLOGY AND PATHOGENESIS
Headache and facial pain are common symptoms of many processes, some of which are not completely understood. They are seen with great frequency in patients of both sexes, of all ages, and from all around the world. Specific forms of headache have their own prevalence, as described later.
By their nature, headache and facial pain are nonspecific symptoms that may be associated with a variety of disorders. In some of these disorders, visual or neurological signs and symptoms may point to a specific diagnosis. These signs and symptoms are discussed under the appropriate diagnostic headache categories.
DIAGNOSIS AND TESTING
Headaches and facial pain, more than any other disease category, are diagnosed through a thorough and intelligent history taking. Hence, the focus in this chapter is on how to take a good history.
The Art and Science of Taking a Headache History
A thorough history is the key to making the correct diagnosis in a headache patient. In most cases, the history generates a limited list of differential diagnoses that can only occasionally be confirmed by physical examination and ancillary studies. To elicit the pertinent clinical information, patients are given the opportunity to describe the symptom complex in detail. Some measure of knowledgeable guidance is required, however, to extract the relevant clinical details and to avoid irrelevant minutiae.
Some patients who have headache and facial pain enter the medical care system with firm preconceptions about the cause of their pain. For example, many have been told by well-meaning friends or relatives that “sinus headaches” or “eye strain” (e.g., because of uncorrected refractive errors) is the source of their discomfort. These misconceptions are reinforced by the over-the-counter market, which strongly promotes analgesic and sympathomimetic preparations for the treatment of “sinus headaches.” However, it rarely is helpful, and often is counterproductive, to point out these apparent misconceptions at the outset. The relevant objective facts should be elicited in a nonchallenging and supportive manner, and a formulation should be deferred until the end of the examination. It is important to keep these preconceptions in mind, however, because they may color the patient’s description of the symptoms; for example, the patient may try to relate all headaches to reading and overlook other contributory factors. To sort out the multitude of factors that can contribute to or cause headaches, it is essential to obtain a relevant past medical history, a basic neurological review of systems ( Box 205-1 ), and a directed headache history (outlined in the next section and in Box 205-2 ).
Basic Outline of the Headache History
DATE OF ONSET, AGE AT ONSET, AND FREQUENCY OF SYMPTOMS.
The length of time that a patient has suffered from headaches is the first guidepost in differentiating benign headaches from those that signify a progressive neurological or systemic disorder and require further investigation. At one end of the spectrum, a pattern of long-standing intermittent headaches with headache-free intervals recurring over months to years is rarely indicative of serious intracranial or systemic pathology. Most of these patients have vascular or stress-tension headaches. Conversely, the sudden onset of severe and persistent headaches in an otherwise headache-free individual, especially when accompanied by focal neurological signs or symptoms, is clearly a cause for concern. Patients experiencing their first attack of migraine may produce confusion in this regard, however, because the initial episode may be accompanied by focal deficits (e.g., hemianopia) but not by the typical signs and symptoms that characterize most recurrent vascular headache episodes.
Some headaches develop, and perhaps progress, over weeks to months. Although most headaches in this category have a benign
Basic Neurological and Neuromuscular Systems Review
INDICATE WHETHER YOU HAVE EVER HAD ANY OF THE FOLLOWING CONDITIONS (check either yes or no).
Chronic, frequent, or very severe headaches
Loss of consciousness
Trouble with speech or comprehension
Paralysis or weakness of arms or legs
Facial palsy (Bell’s palsy)
Persistent numbness or tingling
Sudden or severe loss of vision
Meningitis or encephalitis
Chronic muscle aches (not caused by injury)
Neck stiffness (not caused by injury)
Unexplained fatigue or loss of energy
Pain in your jaw or tongue with chewing
Unexplained weight loss
Scalp tenderness (e.g., when brushing your hair)
This may be completed in advance and reviewed with the patient at the time of the examination.
cause, such as persistent stress-tension or migraine, this is the group of patients in which serious intracranial or systemic pathology should be suspected and carefully ruled out. Headaches that result from intracranial mass lesions or increased intracranial pressure usually have an insidious onset and occur daily, and there are rarely prolonged headache-free intervals.
Stress-tension headaches are often occipital in location and extend to the posterior neck and shoulders ( Fig. 205-1 ). However, intracranial processes, especially in the posterior fossa, can cause a similar distribution of pain. A band-like distribution of pain, which presumably reflects occipitofrontalis tension, also is quite common in patients who have stress-tension headache. Hemicranial headaches that become holocephalic are generally vascular (i.e., migrainous) in nature. Headaches of dental or sinus origin frequently cause frontal, periorbital, or malar pain.
Persistent and unrelenting pain that lasts for days at a time rarely results from vascular or tension headaches; it should arouse suspicion of intracranial disease, sinus inflammation, cranial arteritis, or carotid dissection.
For a minority of patients with vascular headache syndromes, foods or allergens have been identified that precipitate headaches. These include chocolate, red wine, oranges, and fatty foods. In other vascular headache patients, stress—or, more commonly, relief of prolonged stress—triggers a headache episode. Other triggers for vascular headache include bright lights, exercise, sexual intercourse, and alcohol.
Many patients with vascular headaches have some form of autonomic disturbance that precedes their headache by as much as 24 hours. This may include drowsiness, irritability, insomnia, depression, or hypomania. Unformed visual hallucinations occur in 10–15% of migraineurs; typically, these last 10–40 minutes and are followed almost immediately by headache. It is important to differentiate the migrainous visual prodrome from the hallucinations that may occur as epileptiform phenomena in patients who have more serious intracranial disease (see later).
QUALITY AND SEVERITY OF PAIN.
Both vascular headaches and headaches that result from intracranial masses may vary
Basic Outline of the Headache History
Date of onset/age at onset
Frequency of symptoms
Quality and severity of pain
widely in severity, from mild to excruciating. Pain from vascular headache starts out as a dull ache but frequently becomes pulsatile and often is described as throbbing. It may be alleviated by compression or massage of the external carotid artery; usually, it is exacerbated by physical activity. Cluster headaches characteristically are extremely severe. Stress-tension headaches are seldom severe enough to require bed rest and rarely are described as throbbing. Headache from intracranial hemorrhage typically is quite severe and usually is accompanied by focal signs or other neurological symptoms.
Nausea, photophobia, phonophobia (e.g., aversion to sound, especially loud noises), and drowsiness frequently occur during acute migraine headaches and are useful in differentiating vascular from nonvascular paroxysmal headache syndromes. These symptoms also may occur in acute intracranial processes, however, which must be distinguished on the basis of other signs and symptoms. A detailed review of neurological symptoms should be elicited from all headache patients (see Box 205-1 ), which greatly aids in identifying patients who have intracranial inflammation, hemorrhage, or space-occupying lesions.
DIFFERENTIAL DIAGNOSIS OF HEADACHE SYNDROMES
The International Headache Society (IHS) has classified headache and facial pain disorders and provided diagnostic criteria by which various syndromes can be distinguished (a partial listing is given in Box 205-3 ). Although these criteria are tentative and subject to revision, they provide a useful basis on which to develop a working differential diagnosis. At this time, however, no specific diagnostic tests exist for the three most common headache disorders—migraine, tension headache, and cluster headache. The diagnostic criteria, therefore, are highly dependent on an accurate and reliable history.
The terminology for various migraine syndromes may be somewhat inconsistent in the older literature, but most recent publications utilize the more detailed and specific IHS classification. The IHS classification separates migraine patients into those without and with focal neurological symptoms, or “aura,” preceding the headache (categories 1.1 and 1.2, respectively). Categories 1.3–1.5 include several well-recognized but uncommon clinical syndromes in which various types of focal neurological symptoms may occur either before or during the headache. Prolonged attacks, or attacks that result in permanent ischemic damage to the central nervous system, are defined as complications of migraine under category 1.6. These designations are meant to replace the older terms such as “common migraine” for migraine without aura, “classic migraine” for migraine with homonymous hemianopic visual aura, and “complicated migraine” for headaches with nonvisual neurological symptoms that occur during or after the headache phase.
EPIDEMIOLOGY OF MIGRAINE.
The prevalence of migraine has been estimated across various age ranges and in various ethnic and socioeconomic groups. The prevalence estimates are 5–20% for men and 15–40% for women. The prevalence certainly is lower in children but is still substantial.  Dalsgaard-Nielsen
Figure 205-1 Location of pain for common headache syndromes. Tension headache often is described as a feeling of weight in the head or a band-like sensation around the head. The stabbing nature of trigeminal neuralgia is depicted by zigzag lines.
found an equal prevalence of about 3% for boys and girls at age 7 years, which increased to 15% at age 15 years. The first attack of migraine occurs before age 10 years in about 25% of patients, by age 25 years in about 65%, and by age 40 years in more than 90%. Onset in later life does occur, however, and may be confused with transient cerebral ischemia. The criteria used to differentiate migraine equivalents in older patients from transient cerebral ischemic episodes have been discussed at length by Fisher. 
No consistent relationship to ethnic group, socioeconomic status, or personality profile has been found. However, a familial predisposition for migraine clearly exists. One genetic study found a risk of 70% if both parents were affected and 45% if only one parent was affected. The pattern of inheritance appears to be complex and multifactorial.
CLINICAL FEATURES OF VARIOUS MIGRAINE SYNDROMES
Migraine Without Aura (Common Migraine).
Although common migraine is not preceded by focal neurological symptoms (by definition),   many patients notice autonomic or mood disturbances as long as 24 hours before an impending attack. These include irritability, depression, drowsiness, and hunger (sometimes with a craving for specific foods). Other patients may experience hypomania or elation. These premonitory symptoms presumably arise in the hypothalamus; it is interesting in this regard that similar symptoms may be induced by certain 5-hydroxytryptamine (5-HT) antagonists.
The headache phase of common migraine begins unilaterally in only about 50% of patients, often in the periorbital area, and may or may not progress to become holocephalic. The pain may begin anywhere on the head or face, however, and may be bilateral (often bifrontal) at onset. Although many migraineurs report a strong predilection for episodes to occur repeatedly on the same side, most report occasional episodes on the other side. Frequent episodes that involve only one side should arouse suspicion of a space-occupying lesion. The pain often is described as throbbing, usually builds over 1–2 hours, and typically lasts 4–8 hours; however, attacks that last up to 24 hours are not uncommon. The pain usually is exacerbated by routine physical activity, such as bending or minor exertion. Nausea is a prominent feature in 80–90% of migraineurs, but actual vomiting is relatively uncommon. Photophobia and phonophobia are relatively common, and most patients withdraw to a dark, quiet room and lie still during severe attacks. Drowsiness is common, and many patients find that sleep provides substantial relief.
Migraine With Aura (Classic Migraine).
Migraine with aura is characterized by a prodrome consisting of a completely reversible focal neurological symptom that typically lasts 15–45 minutes.   This prodrome is followed by a headache with a duration and quality similar to that of common migraine. The most common prodrome is, of course, the homonymous scintillating scotoma. Less frequently, the aura may consist of a hemisensory disturbance (paresthesia or numbness that involves one side of the body or face), hemiparesis, or dysphasia.   With the exception of the typical homonymous visual aura described later, patients who have focal neurological defects require a neurological consultation to assist in differentiating migraine from more serious transient cerebral ischemia.
The most common description of the visual aura is the perception of multicolored shimmering (scintillating) lights, beginning in the paracentral area and expanding in a crescent-shaped fashion to obscure a large portion of a homonymous hemifield of both eyes ( Fig. 205-2 ). The borders of the scotoma often have jagged edges (teichopsia, or fortification scotoma, in analogy to a medieval fortress). Although the leading edge of the
Partial Listing of the IHS Classification of Headaches (1988)
1.1 Migraine without aura (“common migraine”)
1.2 Migraine with aura
1.2.1 Migraine with typical aura
1.2.2 Migraine with prolonged aura (aura >60 minutes)
1.2.3 Familial hemiplegic migraine
1.2.4 Basilar migraine
1.2.5 Migraine aura without headache (“migraine equivalent,” “migraine disocie”)
1.3 Ophthalmoplegic migraine
1.4 Retinal migraine
1.5 Childhood periodic syndromes (e.g., “abdominal migraine” and “vomiting attacks”)
1.6 Complications of migraine (including migrainous infarction)
1.7 Migraine not fulfilling any of above criteria (“atypical migraine”)
2.0 TENSION-TYPE HEADACHE
2.1 Episodic tension headache
2.1.1 Episodic tension headache with disorder of pericranial muscles (“myofascial syndrome”)
2.1.2 Episodic tension headache without disorder of pericranial muscles
2.2 Chronic tension-type headache
2.2.1 Chronic tension headache with disorder of pericranial muscles (“myofascial syndrome”)
2.2.2 Chronic tension headache without disorder of pericranial muscles
3.0 CLUSTER-TYPE HEADACHE
3.1 Typical cluster headache
3.2 Chronic paroxysmal hemicrania
3.3 Cluster-headache-like disorders (“atypical cluster”)
4.0 MISCELLANEOUS HEADACHES UNASSOCIATED WITH STRUCTURAL, METABOLIC, OR VASCULAR DISORDERS
4.1 Idiopathic stabbing pains (“icepick headaches”)
For the complete classification, see Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia. 1988;8 (Suppl. 7):1–96.
scotoma may be “positive” (i.e., may have flickering imagery that obscures or replaces the normal visual field), the trailing edge of the scotoma is often “negative” (i.e., displays a relatively dark area that fully or partially obscures the visual surround, as illustrated in Figure 205-2 ). Many patients experience a less dramatic and picturesque variant of progressive homonymous visual loss. Other sensations include a gray, black, or colored haze; the perception of a swirling pool of water; and “television interference” or “snow.” A personal report of a migraine episode is described and illustrated nicely by Sacks. 
It is quite common for patients who have homonymous visual loss of any cause to perceive their deficit incorrectly as monocular and ipsilateral to the visual field defect. In patients who report monocular loss, it is imperative to determine whether each eye was checked separately. In most instances, the patient’s report of a negative scotoma with both eyes open is an indication that the episode of visual loss was homonymous rather than monocular.
Treatment of Migraine With and Without Aura.
The current treatment of migraine has been reviewed in detail, and there are several monographs on the subject.  Many patients find that their migraines, with or without aura, can be aborted if they take aspirin, ibuprofen, or caffeine at the first sign of an attack. If this is not effective, sumatriptan, a 5-HT1 -like agonist, is the most effective agent for terminating an acute migraine attack. The drug may be taken orally or subcutaneously in autoinjectable form. Since the introduction of sumatriptan in 1993, several other triptans have been introduced for oral, nasal, and subcutaneous administration. These preparations have similar actions and side
Figure 205-2 Scintillating scotoma in migraine with aura. The leading edge of the scotoma is “positive” (i.e., it consists of bright flickering imagery that obscures or replaces the normal visual field), whereas the trailing edge of the scotoma often is “negative” (i.e., it displays a relatively dark area that fully or partially obscures the visual surround). The illustration depicts a typical fortification scotoma with sharply angulated borders; many other variants of the migraine scotoma may occur (see text).
effect profiles. Their use is reviewed in detail by Evans and Lipton.
For patients who have frequent attacks or who do not respond to sumatriptan, daily treatment for prophylaxis of headache is warranted. Treatment is highly individualized and may include beta blockers, calcium channel blockers, anticonvulsants, or methysergide. Methysergide must be used with extreme caution because of the potential danger of retroperitoneal fibrosis. Because the migrainous aura is associated with decreased cerebral blood flow, it can sometimes be aborted by using a vasodilator. Agents that have proved effective include isoprenaline (inhalant), nitroglycerin (sublingual), and nifedipine (rapidly absorbed after rupture of an ingested capsule containing a 10?mg dose in liquid form). Current controversies in the treatment of migraine are thoroughly discussed in the review by Evans and Lipton. Topics covered include prophylaxis for recurrent or chronic migraine, treatment of basilar or complicated migraine, and use of oral contraceptives in migraine.
Structural Lesions That Mimic Migraine With Aura.
Rarely, structural disease that involves the occipital region is confused with migraine with visual aura. In particular, arteriovenous malformations (AVMs) of the occipital lobe may cause transient homonymous visual loss with scintillating scotoma and headache. In the vast majority of cases, however, these two syndromes may be differentiated on clinical grounds alone. In two large series of occipital AVMs,  none of the patients had the 15–20 minute visual episodes that are characteristic of classic migraine. The headaches in patients with AVMs were consistently localized to the same side. In addition, the visual phenomena often persist intermittently throughout the headache, unlike classic migraine, in which the visual aura is usually complete before the onset of headache.
Troost and Newton studied 26 patients with occipital AVMs and defined two distinct syndromes of visual loss, both of which were clearly differentiated from migraine. The first group of patients had occipital epileptiform discharges and experienced “elementary visual sensations” similar to those experienced on direct cortical stimulation during neurosurgery. Patients with epileptiform activity that originated in the primary visual cortex (area 17) reported small lights moving through the homonymous hemifield. The lights were sometimes colored but did not scintillate and were not associated with the angular or geometrical figures often perceived during migraine. The duration of these lights was rarely in excess of a few minutes. Epileptiform activity that originated in parastriate visual areas 18 and 19 of
the visual cortex tended to cause photopsias that flickered rapidly but lasted only a few seconds to a few minutes at most. Momentary dimming of the homonymous hemifield was sometimes associated with occipital epileptiform activity. In some cases, visual symptoms were followed by a generalized seizure.
The second syndrome consisted of occipital apoplexy associated with hemorrhage of the AVM. This syndrome is characterized by the sudden onset of severe headache with persistent homonymous hemianopia. Other signs of subarachnoid hemorrhage usually are present, including stiff neck, obtundation, disorientation, and loss of consciousness. These hemorrhages typically are quite large and may cause uncal herniation with compression of the ipsilateral posterior cerebral artery, which results in permanent homonymous field loss.
The vast majority of patients with ophthalmoplegic migraine experienced their first attack in early childhood. Although new cases in adults occur, they are quite rare. Ophthalmoplegic migraine almost always involves the third nerve. Rare cases of sixth nerve involvement, and even rarer cases that involve the fourth nerve, have been reported. Bilateral involvement, either simultaneously or sequentially, is quite rare. In 1960 Walsh and O’Doherty  established specific criteria for ophthalmoplegic migraine:
• A prior history of typical common or classic migraine headaches.
• Ophthalmoplegia that occurs during (or, rarely, just before) an established migraine attack.
• Exclusion of other reasonable causes by clinical and radiological studies.
In addition to these criteria, Daroff pointed out that a characteristic abnormality has been demonstrated in all cases of ophthalmoplegic migraine involving the third nerve in which magnetic resonance imaging (MRI) scanning has been performed: thickening and contrast enhancement of the nerve root as it exits the midbrain. This and other clinical findings led Lance and Zagami to postulate that ophthalmoplegic migraine is a recurrent demyelinating, inflammatory cranial neuropathy.
The headache that occurs in ophthalmoplegic migraine is not always severe. It usually begins ipsilaterally but may become bilateral; it lasts from several hours to days. Rarely, the pupil is spared. The ophthalmoplegia usually resolves completely, but residual ptosis and ophthalmoplegia may be present after repeated attacks. Resolution usually requires several weeks or, less commonly, several months.
The differential diagnosis of painful ophthalmoplegia is discussed at length in Chapter 199 . The diagnosis is suspected when parents of children who have this disorder report prior attacks of migraine-like episodes. In practice, when presented with a patient who is undergoing a first episode of pupil-involving third nerve palsy, it is almost always necessary to rule out a compressive third nerve palsy via neuroimaging studies. In most cases, this requires both MRI and cerebral arteriography to rule out an aneurysm.
The cause of ophthalmoplegic migraine is uncertain. Conflicting evidence has been garnered to support an ischemic cause, possibly related to migrainous involvement of the carotid artery; a compressive mechanism, related to compression of the intracavernous or subarachnoid portion of the third nerve by a swollen intracavernous carotid or basilar artery; and a demyelinating and inflammatory cause. The evidence for these disparate, but perhaps complementary, mechanisms is discussed at length by Miller and by Daroff.
Although most visual symptoms in migraine are hemianopic and cortical in origin, transient (rarely permanent) monocular visual loss is well documented.         Both optic nerve  and retinal     ischemic episodes have been reported in migraine. Visual loss in retinal migraine tends to be shorter than that in the occipital variety, typically lasting 5–15 minutes. In some cases, the amaurosis may occur during, rather than before, the headache phase. Retinal vasospasm has been observed ophthalmoscopically during the attack in several patients. Fisher reviewed 138 cases of amaurosis fugax (most without headache) in 1959, in both older and younger patients, and speculated that as many as 17% might be vasospastic in origin.
There seem to be two categories of young patients who experience amaurosis fugax because of presumed or observed vasospasm. The first group includes individuals who have well-established migraine, with or without prior hemianopic auras, and who develop migraine headaches associated with episodes of amaurosis fugax.     The second group consists of patients with no history of migraine who experience episodes of amaurosis fugax. In this group of patients, either vasospasm has been observed or other reasonable causes of amaurosis fugax have been ruled out (presumed retinal vasospasm).   The mechanism of visual loss in this second group is less clear, and its relationship to the dynamics of migraine is less certain than for the first group. Many of the patients in the second group have antiphospholipid antibodies or other evidence of autoimmune disturbance. Nevertheless, patients in this group, like those in the first, tend to respond well to calcium channel blockers or sometimes to aspirin. It has been suggested that retinal vasomotor instability, as a result of a migraine-like mechanism, may be compounded by interference with prostacycline release at the endothelial cell level (in some cases because of antiphospholipid antibodies). This would account for the beneficial effect of both aspirin and calcium channel blockers. However, nonmigraine diagnoses should be excluded in all patients (young and old) who have amaurosis fugax. These diagnoses include embolic disease from the heart and carotid-ophthalmic system, hypercoagulability and hyperviscosity of various causes, and systemic vasculitides (for a detailed discussion of the differential diagnosis of amaurosis fugax, see Chapter 186 ).
PATHOGENESIS OF MIGRAINE.
Although the pathogenesis of migraine remains uncertain, most researchers believe that the vascular alterations are not primary but result from a complex interplay of neuronal, hormonal, hematological, biochemical, and myogenic factors. The major controversies revolve around the mechanisms by which the prodrome, aura, and headache phases are triggered by the following:
• Primary aberrant neuronal activity.
• Various neuropeptides and vasoactive substances.
• Primary alterations in extra- and intracerebral blood flow.
• A combination of the above three factors.
Although an exhaustive discussion of migraine pathogenesis and the interplay of these mechanisms is beyond the scope of this chapter, the major theories are outlined briefly and illustrated in Figure 205-3 . The interested reader is referred to a thorough account in the excellent clinical text by Lance.
General agreement exists, based on epidemiological evidence, that migraineurs have a genetically determined lower threshold for certain environmental (or internal) triggers that can initiate a peculiar cascade of vascular and neurogenic events and lead to a migraine episode. Migraineurs differ from headache-free controls in several aspects of pain control and cerebrovascular reactivity, including the following:
• Altered hypothalamic and brainstem responses to various stimuli, including dopaminergic agonists.
• Altered intra- and extracranial vascular reactivity to stress, exercise, carbon dioxide, and cold stimuli (e.g., brief headache induced by ice cream is much more common in migraineurs).
• Diminished responses at various central nervous system sites to dopaminergic agents.
• Altered platelet function, especially with regard to 5-HT (or serotonin) release.
Several lines of evidence strongly suggest an important role for 5-HT, a powerful vasoactive substance, in the pathogenesis of migraine.  Various studies have shown the following:
• Typical migraine headaches can be produced by intramuscular injection of reserpine, which releases 5-HT from body stores.
• Urinary metabolites of 5-HT are increased during migraines.
• Incubation of platelets with plasma obtained during (but not after) a migraine attack causes the release of 5-HT by platelets.
Figure 205-3 Proposed pathogenesis of migraine. (Based on Lance JW. Migraine: pathophysiology. In: Mechanism and management of headache, 5th ed. London: Butterworth–Heinemann; 1993:91–116; Lance JW, Lambert GA, Goadsby PJ, Zagami AS. Contribution of experimental studies to understanding the pathophysiology of migraine. In: Sandler MP, Collins GM, eds. Migraine. A spectrum of ideas. Oxford: Oxford University Press; 1990:21–39.)
In addition to the receptors involved in the peripheral effect of 5-HT on cranial blood vessels, 5-HT receptors are also found at several important central nervous system sites. These include sites known to affect intra- and extracranial vascular reactivity, as well as sites that mediate the central gating of pain impulses.
Based on both human data and an experimental model, Lance et al.  proposed the mechanism for the development of migraine outlined here. An inherited migraine threshold renders the migraineur unusually susceptible to fluctuations in cortical or hypothalamic function (signaled by mood changes, excessive thirst, hunger, and the like). Once this threshold is reached, the following sequence of events is activated (see Fig. 205-3 ).
Brainstem nuclei, including the nucleus raphe dorsalis (NRD) and the locus ceruleus (LC), are activated by cortical and hypothalamic events. These pathways employ 5-HT and norepinephrine (NE; noradrenaline), respectively, as neurotransmitters. Stimulation of the LC causes constriction of the cortical microcirculation blood vessels via release of the neurotransmitter NE. Stimulation of the LC, the NRD, or the trigeminal nerve may cause dilatation of the extracranial vasculature.
Cortical ischemia produced by microvascular changes may be accompanied by spreading neuronal depression, associated with focal neurological symptoms (e.g., homonymous hemianopia). This accounts for the migrainous aura, which may occur independently of the headache.
Release of 5-HT and vasoactive peptides at nerve endings on blood vessels may induce a sterile inflammatory response, which results in pain. This response may be perpetuated by local axon reflexes or by a central reflex pathway.
Stimulation of the LC also causes release of NE from the adrenals; NE, or an unknown 5-HT–releasing factor, causes platelets to release 5-HT into the circulation. Free 5-HT causes increased sensitivity of vascular receptors, which potentiates both abnormal vascular reactivity and the painful inflammatory response.
Pain afferents from intra- and extracranial vascular structures synapse on second-order neurons in the spinal nucleus of the trigeminal nerve. Transmission at these neurons is regulated in part by the LC, as well as by other brainstem nuclei. Improper activity of the LC may potentiate transmission of pain impulses at these synapses.
Episodic stress-tension headache is the most common form of headache seen in medical practice. Most patients describe their tension headaches as a mild to moderate “pressing” or “squeezing” sensation, or they may compare the pain to a tight band that encircles the scalp. The pain is generally nonpulsatile and almost always bilateral. It may be bifrontal, bioccipital, or “band-like.” Radiation to the posterior neck is common, as is tightness of the jaw muscles. Nausea, photophobia, and phonophobia are absent or minimal. Unlike migraine, tension headaches are not exacerbated by routine physical activity. Also unlike migraine, tension headaches are not preceded by the prodromal constitutional or focal neurological symptoms noted earlier.
Tension headaches may occur as infrequently as once a year and last only 30 minutes, or they may last all day and occur in an unrelenting daily fashion. Most patients who seek medical attention for their tension headaches have episodes that occur several times weekly or monthly, punctuated by headache-free intervals. The presence of headache-free intervals helps differentiate these headaches from more serious pathological processes, also taking into account the absence of other systemic or neurological symptoms. These patients are often aware of stressful emotional triggers that precipitate their tension headaches; therefore, they can readily identify, if not control, the exacerbating factors. Depression is present in up to one third of patients who experience persistent tension headaches. Many patients with tension headaches also have migraines, but usually they can differentiate the two types of headache on the basis of severity, duration, and associated symptoms.
Some controversy exists about the role of the pericranial musculature in the production of tension headache. Although muscle spasm and tenderness may be the result, rather than the primary cause, of chronic tension headaches in many patients, it appears that distinct myofascial trigger points can be a source of pain in some patients. The myofascial pain syndrome is characterized by reproducible pain on palpation of trigger points. The pain generally is referred to a location somewhere along the band of taut muscle that includes the trigger point, although it
may be at some distance from the trigger point itself. According to Jay, the syndromes of tension headache, myofascial pain syndrome, and fibromyalgia represent a spectrum of severity of the same underlying disorder.
Cluster headaches are perhaps the most painful type of “benign” headache. The pain can be so severe that some patients who have this disorder have reported thoughts of suicide. The pain typically is unilateral and periorbital in location and tends to occur on the same side during each attack; rarely is the opposite side involved. Unlike migraines, cluster headaches are more common in men than in women. In addition, cluster patients, unlike migraineurs, generally are hyperactive during an attack—they often pace the room or rock fitfully in a chair. Sympathetic dysfunction ipsilateral to the pain is common.   Horner’s syndrome may be present during the attack, along with lacrimation, conjunctival injection, nasal congestion, rhinorrhea, and eyelid edema. The Horner’s syndrome may persist, especially after repeated attacks; pharmacological testing reveals a postganglionic localization. Attacks are usually shorter than for migraine and last 15–180 minutes, with an average of about 45 minutes. The attacks cluster in time; characteristically, they occur at least once daily, usually at the same time of day. Nocturnal occurrence is common, and the headache often wakes the patient from sleep. Some patients also find that attacks can be precipitated by alcohol ingestion. As the cluster period progresses, the frequency of episodes may increase to three or more per day. The cluster period typically lasts for 4–12 weeks. The patient is then asymptomatic until the next cluster period, which typically occurs a year or more later, usually at the same time of year.
The treatment of cluster headaches is highly individualized and has been reviewed at length elsewhere. Some of the same agents used for migraine may be used for cluster headache, including sumatriptan for acute attacks and methysergide for short-term use (less than 6 months). In addition, prednisone is often effective in halting bouts of cluster headaches. For more resistant cases, lithium is often useful.
Headache is the most common symptom in temporal arteritis ; this diagnosis should be considered in all adults older than 50 years who have headache or facial pain. All patients in this age group should be asked specifically about symptoms of vasculitis and vascular insufficiency that involve the extracranial carotid circulation. These include the following    :
• The presence of pain or tenderness around the temporal arteries.
• Scalp tenderness.
• Pain with chewing (i.e., jaw or tongue claudication).
• Diplopia, which is generally thought to result from extraocular muscle ischemia rather than from cranial neuropathy.
• Transient visual loss as a result of optic nerve or retinal ischemia.
In addition, many but not all patients who have temporal arteritis have symptoms of more widespread rheumatological involvement (i.e., polymyalgia rheumatica).  These symptoms may be rather nonspecific and include malaise and easy fatigability, weight loss, anorexia, and unexplained fevers, as well as proximal myalgias.
The headache of temporal arteritis classically is located over a branch of the superficial temporal artery and is described as a dull ache that persists throughout the day. It may be accompanied by tenderness of the artery and overlying scalp.   The artery, if severely affected, may be indurated and nonpulsatile. Many patients, however, present with a nonspecific unilateral or bilateral headache.
A sedimentation rate to rule out temporal arteritis should be obtained in all patients older than 60 years who have headache
Warning Signs for Headaches Due to Serious Intracranial or Systemic Pathology
New onset headache in a previously headache-free patient
New pattern or new type of headache
“The worst headache I’ve ever had”
Change in personality or mental status
Focal neurological deficit
Signs of meningeal irritation
Recent head trauma
or facial pain, unless the pain obviously results from another cause. The test is simple and noninvasive and identifies about 90% of patients who have this disorder. The consequences of missing this diagnosis (i.e., bilateral visual loss) can be devastating and are usually avoidable with early diagnosis and aggressive treatment. Temporal artery biopsy should be performed in all patients who have a clinically suggestive history, in view of the consequences of an incorrect diagnosis. Unless otherwise contraindicated, corticosteroid therapy should be instituted, pending results of the biopsy. A thorough discussion of the issues that surround diagnosis and therapy of temporal arteritis can be found in Chapter 197 .
Headache as a Result of Intracranial Processes
Ruling out intracranial pathology should be one of the primary goals of the ophthalmologist when a patient complains of headache. Although myriad intracranial processes can cause headache, most intracranial pain is caused by inflammation or stretching of pain-sensitive structures in the dura and blood vessels. For this reason, the pattern of headache in this class of disorders includes several features that can help distinguish them from more benign causes of headache. Although the complete differential diagnosis of intracranial headache is beyond the scope of this chapter, several warning signs should alert the ophthalmologist to the possibility of a serious neurological problem ( Box 205-4 ):
• A change in the usual pattern of headache. Migraine and tension headaches are extremely common and may preexist in patients who develop serious intracranial pathology. An acute or subacute increase in the intensity and frequency of a well-established headache pattern should arouse suspicion, as should the onset of a new type of headache.
• Headache described as “the worst headache I’ve ever had.” Most patients do not use this characterization without good reason, and it often means that the headache is several orders of magnitude greater than prior headaches.
• Headache triggered by exertion, by coughing or sneezing, or by postural changes, such as bending over. These features often signal irritation or stretching of pain-sensitive intracranial structures.
• Headache accompanied by signs of meningeal irritation, such as stiff neck, nausea, vomiting, or fever.
• Headache accompanied by focal or nonfocal neurological signs (e.g., focal weakness or numbness, aphasia, impaired cognitive function, change in personality).
Negative responses to these “red flags” should provide reassurance against intracranial pathology.
The diagnosis of pain that results from acute sinus inflammation is rarely difficult. Often a prior history of sinus inflammation or respiratory allergies is elicited. In general, the pain is of low to moderate intensity and is present on a daily basis. The pain usually is localized to the frontal or maxillary area, and there is tenderness to percussion over the affected sinus. The pain is often
worsened by bending forward and may be accentuated by blowing the nose or sneezing. Symptoms of nasal “stuffiness” are usually present, and mucopurulent drainage from the nostrils may be seen. If the nasal passages are blocked, use of a nasal decongestant can be useful diagnostically and often results in discharge. In doubtful cases, a simple plain film of the sinuses or an opinion from an otolaryngologist should be obtained.
Tumors, abscesses, and mucoceles that arise in the sinuses and nasopharynx can give rise to facial or periorbital pain. Mucoceles, in particular, tend to cause pain by obstructing sinus ostia. Maxillary (and, less commonly, sphenoid) mucoceles may erode the orbital bones and cause proptosis. Sphenoid mucoceles may invade the orbital apex, which results in ocular motility disturbances or optic neuropathy. Nasopharyngeal carcinoma has a propensity to invade the base of the skull by traveling along neural foramina. These tumors may cause ocular motility disturbances, most commonly sixth nerve palsy; however, their most common neuro-ophthalmological manifestation is facial numbness or pain. Decreased hearing as a result of closure of the eustachian tube also is common. These tumors can be missed easily on plain films and require computed tomography or MRI for early detection.
Orbital Inflammation and Neoplasia
Although the physical examination and differential diagnosis of orbital disease are beyond the scope of this chapter, the classic signs and symptoms should be elicited meticulously whenever orbital disease is suspected (see Chapter 95 ). A presumptive diagnosis of orbital inflammatory or neoplastic disease usually can be made on the basis of a thorough history and examination and is confirmed with radiological studies. Difficulties arise primarily in patients whose signs of orbital disease are minimal. For example, small posterior orbital masses, such as optic nerve sheath meningiomas, may cause little exophthalmos. However, careful testing of visual function, including color vision and pupillary function, almost always demonstrates convincing evidence of a subtle optic neuropathy. Orbital myositis and inflammatory orbital pseudotumor ordinarily cause persistent unilateral pain of moderate to severe intensity, and signs of ocular proptosis or dysmotility usually are present.
Posterior scleritis may be difficult to diagnose. The pain is persistent and often moderately severe. It may be accentuated by eye movement. Quantitative A-scan ultrasonography usually is diagnostic and demonstrates thickening of the affected sclera. B-scan ultrasonography is not quite as sensitive but may be helpful. Though not ordinarily necessary, computed tomography scans generally show thickening and enhancement of the affected posterior sclera.
DIFFERENTIAL DIAGNOSIS OF FACIAL PAIN
Facial pain may arise from a variety of structures of the face and neck, including the sinuses, nasopharynx, teeth and gums, facial muscles, orbit, middle ear, trigeminal nerve, muscles of mastication, and carotid artery and its tributaries. Several syndromes can include ocular or periorbital pain and should be familiar to the ophthalmologist.
Trigeminal Neuralgia (Tic Douloureux)
Trigeminal neuralgia is characterized by sudden, intense jabs of pain that last only a few seconds or less. The pain generally is limited to one of the three divisions of the trigeminal nerve, with the second and third divisions involved most frequently. The pain usually is described as lancinating or “stabbing” in quality; it often recurs in a series of paroxysms that extend over several minutes. Most patients can identify a triggering activity, such as chewing, swallowing, or light touch to a part of the face, that initiates a paroxysm.
Figure 205-4 MRI of spontaneous carotid dissection. A, T2-weighted MRI through the base of the skull demonstrates normal flow void in the right internal carotid (large arrow) and curvilinear high signal intensity in the left internal carotid (small arrow) caused by spontaneous dissection in a 52-year-old hypertensive man. B, Magnetic resonance angiogram in the anterior oblique projection demonstrates an area of narrowing of the internal carotid artery due to dissection (arrow) just distal to the bifurcation.
Raeder’s Paratrigeminal Syndrome
In 1924 Raeder described a series of patients who had oculosympathetic paresis (Horner’s syndrome) and pain in the trigeminal distribution. Raeder’s series actually included two different types of patients. The first group had episodic headaches caused by what is now known as the cluster headache syndrome. The second group had chronic pain in the trigeminal distribution caused by a variety of space-occupying lesions, including tumors of the middle cranial fossa. In this latter group, oculosympathetic paresis resulted from involvement of the sympathetic plexus with the internal carotid artery, either at the base of the skull or in the cavernous sinus. The term “Raeder’s paratrigeminal syndrome” generally should not be used. This avoids confusion between the benign cluster headache syndrome, on the one hand, and potentially lethal skull base tumors or aneurysms, on the other.
All patients with suspected oculosympathetic paresis should undergo a cocaine test for confirmation and a hydroxyamphetamine test for localization (see Chapter 203 ). These tests should be followed by appropriate neuroimaging of either the base of the skull and upper neck (for postganglionic lesions) or the chest and neck (for preganglionic lesions). Trigeminal sensation should be checked in all three divisions. Trigeminal hypesthesia is not a feature of the cluster headache syndrome and should alert the clinician to the possibility of a mass lesion or microscopic infiltration at the skull base. In patients who have facial pain and Horner’s syndrome, the clinician should be particularly aware of the signs and symptoms of dissection of the internal carotid artery. Dysesthesia of the scalp and dysgeusia, or unpleasant taste, are common, along with postganglionic Horner’s syndrome. Although spontaneous dissections occur, most middle-aged or older patients are hypertensive, and most younger patients have had significant neck trauma. The condition usually is diagnosed readily with MRI ( Fig. 205-4 ).
Chronic Paroxysmal Hemicrania
Normally classified as a cluster headache variant, this unusual syndrome is characterized by episodes of multiple, brief “stabbing” pains, typically in the periorbital region. The pain usually
is quite severe and lasts 1–2 minutes, but a series of paroxysms may last up to 45 minutes. Repeated series tend to occur throughout the day, as often as 10–15 times. Episodes are accompanied by hemicranial autonomic dysfunction similar to that seen with cluster headaches. The syndrome often responds to indomethacin 25–50?mg three times daily.
Icepick Headaches (Jabs and Jolts Syndrome)
This syndrome consists of intense stabbing pains that last only a few seconds and typically occur in the periorbital region, forehead, or frontal area. This type of pain is seen in about one third of migraineurs and may accompany a migraine episode or occur independently. When this type of headache occurs independently of migraine episodes, it usually is quite responsive to indomethacin.
1. McQueen J, Loblay RH, Swain AR, et al. A controlled trial of dietary modification in migraine. In: Rose FC, ed. New advances in headache research. London: Smith-Gordon; 1989:235–42.
2. Drummond PD, Lance JW. Neurovascular disturbances in headache patients. Clin Exp Neurol. 1984;20:93–9.
3. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia. 1988;8(Suppl. 7):1–96.
4. Dalsgaard-Nielsen J. Some aspects of the epidemiology of migraine in Denmark. Headache. 1970;10:14–23.
5. Mortimer MJ, Kay J, Jaron A. Childhood migraine in general practice: clinical features and characteristics. Cephalalgia. 1992;12:238–43.
6. Lance JW, Curran DA, Anthony M. Investigation into the mechanism and treatment of chronic headache. Med J Aust. 1965;65:909–14.
7. Fisher CM. Late-life migraine accompaniments as a cause of unexplained transient ischemic attacks. Can J Neurol Sci. 1980;7:9–17.
8. Laurence KM. Genetics of migraine. In: Blau JN, ed. Migraine. Clinical and research aspects. Baltimore: Johns Hopkins University Press; 1987:479–84.
9. Lance JW. Migraine: clinical aspects. In: Mechanism and management of headache, 5th ed. London: Butterworth–Heinemann; 1993:68–90.
10. Evans RW, Lipton RB. Topics in migraine management: a survey of headache specialists highlights some controversies. Neurol Clin. 2001;19:1–21.
11. Solomon S, Cappa KG, Smith CR. Common migraine: criteria for diagnosis. Headache. 1988;28:124–9.
12. Sicuteri F. Prophylactic and therapeutic properties of UML-491 in migraine. Int Arch Allergy. 1959;15:300–7.
13. Hupp SL, Kline LB, Corbett JJ. Visual disturbances of migraine. Surv Ophthalmol. 1989;33:221–36.
14. Corbett JJ. Neuro-ophthalmic complications of migraine and cluster headaches. Neurol Clin. 1983;1:973–5.
15. Iversen HK, Langemark M, Andersson PG, et al. Clinical characteristics of migraine and episodic tension-type headache in relation to old and new diagnostic criteria. Headache. 1990;30:514–9.
16. Miller NR. Migraine. In: Walsh and Hoyt’s clinical neuro-ophthalmology, vol 4, 4th ed. Baltimore: Williams & Wilkins; 1991:2515–74.
17. Sacks O. Migraine aura and classical migraine. In: Migraine. The evolution of a common disorder. Berkeley: University of California Press; 1970:72–117.
18. Lance JW. Migraine: treatment. In: Mechanism and management of headache, 5th ed. London: Butterworth–Heinemann; 1993:116–43.
19. Troost BT, Newton TH. Occipital lobe arteriovenous malformations: clinical and radiologic features in 26 cases with comments on the differentiation from migraine. Arch Ophthalmol. 1975;93:250–6.
20. Bruyn GW. Intracranial arteriovenous malformation and migraine. Cephalalgia. 1984;4:191–207.
21. Walsh JP, O’Doherty DS. A possible explanation of the mechanism of ophthalmoplegic migraine. Neurology. 1960;10:1079–84.
22. Daroff RB. Ophthalmoplegic migraine. Cephalalgia. 2001;1:81.
23. Lance JW, Zagami AS. Ophthalmoplegic migraine: a recurrent demyelinating neuropathy? Cephalalgia. 2001;21:84–9.
24. Glenn AM, Shaw PJ, Howe JW, Bates D. Complicated migraine resulting in blindness due to bilateral retinal infarction. Br J Ophthalmol. 1992;76:189–90.
25. Weinstein JM, Feman SS. Ischemic optic neuropathy in migraine. Arch Ophthalmol. 1982;100:1097–100.
26. Katz B. Bilateral sequential migrainous ischemic optic neuropathy. Am J Ophthalmol. 1985;99:489.
27. Fisher CM. Observation of the fundus oculi in transient monocular blindness. Neurology. 1959;9:333–47.
28. Winterkorn JMS, Kupersmith MJ, Wirtschafter JD, Forman S. Brief report: treatment of vasospastic amaurosis fugax with calcium-channel blockers. N Engl J Med. 1993;329:396–8.
29. Burger SK, Saul RF, Selhorst JB, Thurston SE. Transient monocular blindness caused by vasospasm. N Engl J Med. 1991;325:870–3.
30. Winterkorn JMS, Teman AJ. Recurrent attacks of amaurosis fugax treated with calcium channel blockers. Ann Neurol. 1991;30:423–5.
31. McLean PM, Greco TP. Amaurosis fugax (letter). N Engl J Med. 1994;330(2):144. Comment on: N Engl J Med. 1993;329(6):426–8.
32. Lance JW. Migraine: pathophysiology. In: Mechanism and management of headache, 5th ed. London: Butterworth–Heinemann; 1993:91–116.
33. Lance JW, Lambert GA, Goadsby PJ, Zagami AS. Contribution of experimental studies to understanding the pathophysiology of migraine. In: Sandler MP, Collins GM, eds. Migraine. A spectrum of ideas. Oxford: Oxford University Press; 1990:21–39.
34. Jay GW. Pathophysiology of tension type headache. In: Tollison CD, Kunkel RS, eds. Headache. Diagnosis and treatment. Baltimore: Williams & Wilkins; 1991: 129–42.
35. Jay GW. Myofascial mechanisms in the etiology of chronic daily headache: two syndromes, one entity? Paper presented at the 32nd annual meeting of the American Association for the Study of Headache, Los Angeles, June 1990.
36. Lance JW. Cluster headache. In: Mechanism and management of headache, 5th ed. London: Butterworth–Heinemann; 1993:163–87.
37. Nordborg E, Nordborg C, Malmvall BE, et al. Giant cell arteritis. Rheum Dis Clin North Am. 1995;21(4):1013–26.
38. Keltner JL. Giant-cell arteritis. Signs and symptoms. Ophthalmology. 1982;89: 1101–10.
39. Hellmann DB. Immunopathogenesis, diagnosis, and treatment of giant cell arteritis, temporal arteritis, polymyalgia rheumatica, and Takayasu’s arteritis. Curr Opin Rheumatol. 1993;5:25–32.
40. Miller NR. Giant cell arteritis. In: Walsh and Hoyt’s clinical neuro-ophthalmology, vol 4, 4th ed. Baltimore: Williams & Wilkins; 1991:2601–27.
41. Kyle V, Cawston TE, Hazleman BL. Erythrocyte sedimentation rate and C reactive protein in the assessment of polymyalgia rheumatica/giant cell arteritis on presentation and during follow up. Ann Rheum Dis. 1989;48:667–71.
42. Smith JJ, Wheliss JA. Ocular manifestations of nasopharyngeal tumors. Trans Am Acad Ophthalmol Otolaryngol. 1962;66:659–64.
43. Benson WE. Posterior scleritis. Surv Ophthalmol. 1988;32:297–316.
44. Fromm GH, Terrence CF, Maroon JC. Trigeminal neuralgia. Current concepts regarding etiology and pathogenesis. Arch Neurol. 1984;41:1204–7.
45. Raeder JG. “Paratrigeminal” paralysis of oculopupillary sympathetics. Brain. 1924;47:149–58.
46. Pozzati E, Giuliani G, Poppi M, Faenza A. Long-term follow-up of occlusive cervical carotid dissection. Stroke. 1989;20:412–6.
47. Sjaastad O, Apfelbaum R, Caskey W, et al. Chronic paroxysmal hemicrania (CPH). The clinical manifestations. A review. Ups J Med Sci. 1980;31(Suppl.):27–33.
48. Raskin NH, Schwartz RK. Icepick-like pain. Neurology. 1980;30:203–5.