Chapter 6: Headache & Facial Pain

Headache occurs in all age groups and accounts for 1% to 2% of emergency department evaluations and up to 4% of medical office visits; the causes are myriad (Table 6-1). Although most often a benign condition (especially when chronic and recurrent), headache of new onset may be the earliest or the principal manifestation of serious systemic or intracranial disease and therefore requires thorough and systematic evaluation.

An etiologic diagnosis of headache is based on understanding the pathophysiology of head pain; obtaining a history, with characterization of the pain as acute, subacute, or chronic; performing a careful physical examination; and formulating a differential diagnosis.

PATHOPHYSIOLOGY OF HEADACHE & FACIAL PAIN

PAIN-SENSITIVE STRUCTURES

Headache is caused by traction, displacement, inflammation, or distention of the pain-sensitive structures in the head or neck. Isolated involvement of the bony skull, most of the dura, or most regions of brain parenchyma does not produce pain.

A. Pain-Sensitive Structures Within the Cranial Vault

These include the venous sinuses (eg, sagittal sinus); anterior and middle meningeal arteries; dura at the base of the skull; trigeminal (V), glossopharyngeal (IX), and vagus (X) nerves; proximal portions of the internal carotid artery and its branches near the circle of Willis; brainstem periaqueductal gray matter; and sensory nuclei of the thalamus.

B. Extracranial Pain-Sensitive Structures

These include periosteum of the skull; skin; subcutaneous tissues, muscles, and arteries; neck muscles; second (C2) and third (C3) cervical nerves; eyes, ears, teeth, sinuses, and oropharynx; and mucous membranes of the nasal cavity.

RADIATION OR PROJECTION OF PAIN

1. The trigeminal (V) nerve carries sensation from intracranial structures in the anterior and middle fossae of the skull (above the cerebellar tentorium). Discrete intracranial lesions in these locations can produce pain that radiates in the trigeminal nerve distribution (Figure 6-1).

2. The glossopharyngeal (IX) and vagus (X) nerves convey sensation from part of the posterior fossa; pain originating in this area may also be referred to the ear or throat, as in glossopharyngeal neuralgia.

3. The upper cervical (C2-C3) nerves transmit stimuli from infratentorial and cervical structures; therefore, pain from posterior fossa lesions often projects to the second and third cervical dermatomes (see Figure 6-1).

HISTORY

CLASSIFICATION & APPROACH TO THE DIFFERENTIAL DIAGNOSIS

A. Acute Headache & Facial Pain

Headaches that are new in onset or clearly different from any the patient has experienced previously are commonly a symptom of serious illness and demand prompt evaluation. The sudden onset of “the worst headache I’ve ever had in my life” (classically due to subarachnoid hemorrhage), neck and facial pain (cervical arterial dissection), diffuse headache with neck stiffness and fever (meningitis), and head pain centered about one eye (acute glaucoma) are striking examples. Acute headaches may also accompany more benign processes such as systemic viral infections or other febrile illnesses.

B. Subacute Headache & Facial Pain

Subacute headaches are those that persist or recur over weeks to months. Such headaches may also signify serious medical disorders, especially when the pain is progressive or when it occurs in elderly patients. Patients with subacute headache should be asked about recent head trauma (subdural hematoma or postconcussive syndrome); malaise, fever, or neck stiffness (subacute meningitis); focal neurologic abnormalities or weight loss (primary or metastatic brain tumor); visual changes (giant cell arteritis, idiopathic intracranial hypertension); or medications predisposing to headache (nitrates).

C. Chronic Headache & Facial Pain

Headaches that have recurred over years (eg, migraine or tension-type headaches) usually have a benign cause, although each acute attack may be profoundly disabling. When treating these patients, it is important to determine whether the present headache is similar to those suffered previously or is new—and thus represents a different process.

PRECIPITATING FACTORS

Precipitating factors can provide a guide to the cause of chronic headache. Such factors include: dental surgery; acute exacerbation of chronic sinusitis or hay fever; systemic viral infection; psychologic tension, emotional stress, or fatigue; menses; hunger; fasting; consumption of ice cream or foods containing nitrite (hot dogs, salami, ham, and most sausage), phenylethylamine (chocolate), or tyramine (cheddar cheese); and exposure to bright lights. Precipitation of headache by alcohol is especially typical of cluster headache. Chewing and eating commonly trigger pain associated with glossopharyngeal neuralgia and tic douloureux; jaw claudication is associated with giant cell arteritis or temporomandibular joint dysfunction. Oral contraceptive agents and nitrates may precipitate or exacerbate migraine. Headache may also be provoked by coughing or sneezing, especially in patients with structural lesions in the posterior fossa. Posttraumatic headaches begin within a week of head trauma and are most often migrainous in nature.

PRODROMAL SYMPTOMS (AURAS)

Prodromal symptoms or auras, such as scintillating scotomas or other visual changes, often occur with migraine; they may also occur in patients with seizure disorders and postictal headaches.

CHARACTERISTICS OF PAIN

Headache or facial pain may be described in a variety of ways. Pulsating or throbbing pain is characteristic of migraine. A steady sensation of tightness or pressure is commonly seen with tension-type headache. Neck discomfort may occur in migraine due to the convergence of trigeminal and cervical pain pathways within the brainstem. The pain produced by intracranial mass lesions is typically dull and steady. Sharp, lancinating (stabbing) pain suggests a neuritic cause such as trigeminal neuralgia. Icepick-like pain may be described also by patients with migraine, cluster headache, or giant cell arteritis.

Headache of virtually any description can occur in patients with migraine or brain tumors; therefore, the character of the pain alone does not provide a reliable etiologic guide.

LOCATION OF PAIN

1. Unilateral headache is an invariable feature of cluster headache and occurs in the majority of migraine attacks; most patients with tension-type headache report bilateral pain.

2. Ocular or retro-orbital pain suggests a primary ophthalmic disorder such as acute iritis or glaucoma, optic (II) nerve disease (eg, optic neuritis), or retro-orbital inflammation (eg, Tolosa–Hunt syndrome). It is also common in migraine or cluster headache.

3. Paranasal pain localized to one or several sinuses, often associated with tenderness of the overlying periosteum and skin, occurs with acute sinus infection or outlet obstruction.

4. Focal headache may result from intracranial mass lesions, but even in such cases it is replaced by bioccipital and bifrontal pain when the intracranial pressure becomes elevated.

5. Bandlike or occipital discomfort is commonly associated with tension-type headache. Occipital localization can also occur with meningeal irritation from infection or hemorrhage and with disorders of the joints, muscles, or ligaments of the upper cervical spine.

6. Pain within the first (V1) division of the trigeminal nerve, characteristically described as burning in quality, is a common feature of postherpetic neuralgia.

7. Lancinating pain localized to the second (V2) or third (V3) division of the trigeminal (V) nerve suggests trigeminal neuralgia (tic douloureux).

8. The pharynx and external auditory meatus are the most frequent sites of pain caused by glossopharyngeal neuralgia.

ASSOCIATED SYMPTOMS

Manifestations of underlying systemic disease can aid in the etiologic diagnosis of headache and should always be sought.

1. Recent weight loss may accompany cancer, giant cell arteritis, or depression.

2. Fever or chills may indicate systemic infection or meningitis.

3. Dyspnea or other symptoms of heart disease raise the possibility of subacute infective endocarditis and resultant brain abscess.

4. Visual disturbances suggest an ocular disorder (eg, glaucoma), migraine, or an intracranial process involving the optic nerve (optic neuritis) or tract or central visual pathways.

5. Nausea and vomiting are common in migraine and posttraumatic headache and can also be seen with intracranial mass lesions. Some patients with migraine report that diarrhea or other gastrointestinal symptoms accompany attacks.

6. Photophobia may be prominent in migraine, acute meningitis, or subarachnoid hemorrhage.

7. Myalgias often accompany tension-type headache, systemic viral infections, and giant cell arteritis.

8. Ipsilateral rhinorrhea and lacrimation during attacks typify cluster headache.

9. Transient loss of consciousness may be seen in both migraine (basilar migraine) and glossopharyngeal neuralgia (due to cardiac syncope; Chapter 12, Seizures & Syncope).

OTHER FEATURES OF HEADACHE

A. Temporal Pattern of Headache

Headaches from mass lesions are commonly increased by bending over, as are sinus headaches. Headaches from mass lesions, however, increase in severity over time. Cluster headaches frequently awaken patients from sleep; they often recur at the same time each day or night. Tension-type headaches can develop whenever stressful situations occur and are often maximal at the end of a workday. Migraine headaches are episodic and may be worse during menses (Figure 6-2).

B. Conditions Relieving Headache

Migraine headaches are frequently relieved by darkness, sleep, vomiting, or pressing on the ipsilateral temporal artery, and their frequency may diminish during pregnancy. Post-lumbar-puncture and low-pressure headaches are typically relieved by recumbency, whereas headaches caused by intracranial mass lesions may be less severe with the patient standing.

C. Conditions Exacerbating Headache

Discomfort exacerbated by rapid changes in head position such as bending over or by events that transiently raise intracranial pressure, such as coughing and sneezing, is often associated with an intracranial mass but can also occur in migraine. Anger, excitement, or irritation can precipitate or worsen both migraine and tension-type headaches. Stooping, bending forward, sneezing, or blowing the nose characteristically worsens the pain of sinusitis. Postural headache (maximal when upright, nearly absent when lying down) occurs with low cerebrospinal fluid (CSF) pressure caused by lumbar puncture, head injury, or spontaneous spinal fluid leak. Fluctuations in intensity and duration of the headache with no obvious cause, especially when associated with similar fluctuations in mental status, are seen with subdural hematoma.

D. History of Headache

The characteristics of the present headache should be compared with those of previous occurrences, because headache with features different from those previously experienced calls for especially careful investigation.

PHYSICAL EXAMINATION

A general physical examination is mandatory, because headache is a nonspecific accompaniment of many systemic disorders. If possible, the patient should be observed during an episode of headache or facial pain.

VITAL SIGNS

A. Temperature

Although fever suggests a viral syndrome, meningitis, encephalitis, or brain abscess, headache from these causes can also occur without fever. Moreover, headache can accompany many systemic infections.

B. Pulse

Tachycardia can occur in a tense, anxious patient with a tension-type headache or accompany any severe pain. Paroxysmal headache associated with tachycardia and perspiration is characteristic of pheochromocytoma.

C. Blood Pressure

Hypertension per se rarely causes headache unless the blood pressure elevation is acute, as with pheochromocytoma, or very high, as with hypertensive encephalopathy. Chronic hypertension, however, is the major risk factor for hemorrhagic or ischemic stroke, which can be associated with acute headache. Subarachnoid hemorrhage is commonly followed by marked acute elevation of blood pressure.

D. Respiration

Hypercapnia from respiratory insufficiency of any cause can elevate intracranial pressure and produce headache.

GENERAL PHYSICAL EXAMINATION

A. Weight Loss

Weight loss or cachexia in a patient with headache suggests cancer or chronic infection. Polymyalgia rheumatica and giant cell arteritis can also be accompanied by weight loss.

B. Skin

Focal inflammation (cellulitis) of the face or overlying the skull indicates local infection, which may be the source of intracranial abscess or cause venous sinus thrombosis. Cutaneous abnormalities elsewhere may suggest vasculitis (including that from meningococcemia), endocarditis, or cancer. The neurofibromas or café-au-lait spots of von Recklinghausen disease (neurofibromatosis) may be associated with benign or malignant intracranial tumors that can produce headache. Cutaneous angiomas sometimes accompany arteriovenous malformations (AVMs) of the central nervous system, which may be associated with chronic headache—or acute headache if they bleed. Herpes zoster that affects the face and head most often involves the eye and the skin around the periorbital tissue, causing facial pain.

C. Scalp, Face, & Head

Scalp tenderness is characteristic of migraine headache, subdural hematoma, giant cell arteritis, and postherpetic neuralgia. Nodularity, erythema, or tenderness over the temporal artery suggests giant cell arteritis. Localized tenderness of the superficial temporal artery also accompanies acute migraine. Recent head trauma or a mass lesion can cause a localized area of tenderness. Trauma causes characteristic ecchymosis (see Figure 1-4).

Paget disease, myeloma, or metastatic cancer of the skull may produce head pain that is boring in quality and associated with skull tenderness. In Paget disease, arteriovenous shunting within bone may make the scalp feel warm.

Disorders of the eyes, ears, or teeth may cause headache. Tooth percussion may reveal periodontal abscess. Sinus tenderness may indicate sinusitis. A bruit over the orbit or skull suggests an intracranial AVM, carotid artery-cavernous sinus fistula, aneurysm, or meningioma. Lacerations of the tongue raise the possibility of postictal headache. Ipsilateral conjunctival injection, lacrimation, Horner syndrome (see Chapter 7, Neuro-Ophthalmic Disorders), and rhinorrhea occur with cluster headache. Temporomandibular joint disease is accompanied by local tenderness and crepitus over the joint. Jaw claudication is characteristic of temporal arteritis.

D. Neck

Cervical muscle spasm occurs with tension-type and migraine headaches, cervical spine injuries, cervical arthritis, or meningitis. Carotid bruits may be associated with cerebrovascular disease.

Meningeal signs must be sought carefully, especially if headache is of recent onset. Meningeal irritation causes nuchal (neck) rigidity mainly in the anteroposterior direction, whereas cervical spine disorders restrict movement in all directions. Discomfort or hip and knee flexion during neck flexion (Brudzinski sign) indicates meningeal irritation (see Figure 1-5). Meningeal signs may be absent or difficult to demonstrate in the early stages of subacute (eg, tuberculous) meningitis, in the first few hours after subarachnoid hemorrhage, and in comatose patients.

E. Heart & Lungs

Brain abscess may be associated with congenital heart disease, which may be evidenced by heart murmur or cyanosis. Lung abscess may also be a source of brain abscess.

NEUROLOGIC EXAMINATION

A. Mental Status Examination

During the mental status examination, patients with acute headache may be confused, as is commonly seen with subarachnoid hemorrhage and meningitis. Headache with symptoms of dementia may be indicative of intracranial tumor, particularly one in the frontal lobe or infiltrating across the corpus callosum.

B. Cranial Nerve Examination

Cranial nerve abnormalities can suggest and localize an intracranial tumor or other mass lesion. Papilledema, the hallmark of increased intracranial pressure, may be seen with space-occupying intracranial lesions, carotid artery-cavernous sinus fistula, pseudotumor cerebri, or hypertensive encephalopathy. Superficial retinal hemorrhages (subhyaloid hemorrhages) are characteristic of subarachnoid hemorrhage in adults (Figure 6-3). Ischemic retinopathy may be found in patients with vasculitis.

Progressive oculomotor (III) nerve palsy, especially when it causes pupillary dilatation, may be the presenting sign of an expanding posterior communicating artery aneurysm; alternatively, it may reflect increasing intracranial pressure and incipient brain herniation. Decreased pupillary reactivity to light occurs in optic neuritis. Extraocular muscle palsies occur in Tolosa–Hunt syndrome (see Chapter 7, Neuro-Ophthalmic Disorders). Proptosis suggests an orbital mass lesion or carotid artery-cavernous sinus fistula.

Decreased sensation over the site of facial pain—most commonly the first (V1) division of the trigeminal (V) nerve—is found in postherpetic neuralgia. Trigger areas on the face and pharynx suggest trigeminal and glossopharyngeal neuralgia, respectively.

C. Motor Examination

Asymmetric motor function or gait ataxia in a patient with a history of subacute headache demands complete evaluation to exclude intracranial mass lesions.

D. Sensory Examination

Focal or segmental sensory impairment or diminished corneal sensation (corneal reflex) is strong evidence against a benign cause of pain.

Sudden onset of a new headache may be a symptom of serious intracranial or systemic disease; it must be investigated promptly and thoroughly.

SUBARACHNOID HEMORRHAGE

Spontaneous (nontraumatic) subarachnoid hemorrhage (bleeding into the subarachnoid space) is usually the result of a ruptured cerebral arterial aneurysm or an AVM.

Rupture of a saccular (berry) aneurysm accounts for approximately 75% of cases of subarachnoid hemorrhage, with an annual incidence of 6 per 100,000. Most arise sporadically, but some are familial. Families with two or more affected persons should have all members screened. Both autosomal and recessive patterns of inheritance occur.

Rupture occurs most often during the fifth and sixth decades; sex distribution is approximately equal. The risk of rupture of an intracranial aneurysm varies with the patient’s age and the site and size of the aneurysm; approximately 5% of autopsied individuals have cerebral aneurysms, and most have never experienced symptoms. Hypertension has not been conclusively demonstrated to predispose to the development of aneurysms, but acute elevation of blood pressure (eg, at orgasm) may be responsible for aneurysm rupture.

Fusiform aneurysms result from circumferential dilation of a cerebral arterial trunk. In contrast to saccular aneurysms, they are thought to be caused by atherosclerosis or dissection, affect the vertebrobasilar system preferentially, and can present with symptoms of ischemia or mass effect, in addition to rupture.

Intracranial AVMs, a less frequent cause of subarachnoid hemorrhage (10%), occur twice as often in men as in women, and usually bleed in the second to fourth decades, although a significant incidence extends into the sixties. Blood in the subarachnoid space can also result from intracerebral hemorrhage, embolic stroke, and trauma.

PATHOLOGY

Cerebral arterial aneurysms are usually congenital and result from developmental weakness of the vessel wall, especially at sites of branching. They typically arise from intracranial arteries about the circle of Willis at the base of the brain (Figure 6-4), occur in 2% of patients, and are multiple in approximately 20% of cases. Other congenital abnormalities, such as polycystic kidney disease or coarctation of the aorta, may be associated with berry aneurysms.

Occasionally, systemic infections such as infective endocarditis disseminate to a cerebral artery and cause aneurysm formation; such mycotic aneurysms account for 2% to 3% of aneurysmal ruptures. Mycotic aneurysms are usually more distal along the course of cerebral arteries than are berry aneurysms.

AVMs consist of abnormal vascular communications that permit arterial blood to enter the venous system without passing through a capillary bed. They are most common in the middle cerebral artery distribution.

PATHOPHYSIOLOGY

Rupture of an intracranial artery elevates intracranial pressure and distorts pain-sensitive structures, producing headache. Intracranial pressure may reach systemic perfusion pressure and acutely decrease cerebral blood flow; together with the concussive effect of the rupture, this is thought to cause the loss of consciousness that occurs at the onset in approximately 50% of patients. Rapid elevation of intracranial pressure can also produce subhyaloid retinal hemorrhages (see Figure 6-3).

CLINICAL FINDINGS

A. Symptoms & Signs

The classic (but not invariable) presentation of subarachnoid hemorrhage is with the sudden onset of an unusually severe generalized headache, classically described as the worst headache the patient has ever experienced. However, among patients presenting with the abrupt onset of an unusually severe headache, only 8% to 10% will have subarachnoid hemorrhage (see also reversible cerebral vasoconstriction syndrome characterized by recurrent thunderclap headache in Chapter 13). Abrupt onset to maximal intensity is the essential feature of subarachnoid hemorrhage headache. The absence of headache essentially excludes the diagnosis. One-third of patients present with headache alone. In the remainder, loss of consciousness is frequent at onset, as are vomiting and neck stiffness. Symptoms may begin at any time of day and during either rest or exertion.

The most significant feature of the headache is that it is new. Milder but otherwise similar headache (sentinel headache) may have occurred in the weeks prior to the acute event and probably represent small prodromal hemorrhages or aneurysmal stretch.

The headache is not always severe, especially if hemorrhage is from a ruptured AVM rather than an aneurysm. Although the duration of the hemorrhage is brief, the intensity of the headache may remain unchanged for several days and may subside slowly over approximately 2 weeks. Recurrence of the headache usually signifies rebleeding.

Blood pressure frequently rises precipitously as a result of the hemorrhage. Meningeal irritation may induce temperature elevations up to 39°C (102.2°F) during the first 2 weeks. There is frequently associated confusion, stupor, or coma. Nuchal rigidity and other evidence of meningeal irritation (see Figure 1-5) are common, but may not occur for several hours after the onset of headache. Preretinal globular subhyaloid hemorrhages (found in 20%-40% of cases; see Figure 6-3) are most suggestive of the diagnosis.

With aneurysmal rupture, bleeding occurs mainly in the subarachnoid space rather than within brain parenchyma. Therefore, prominent focal neurologic signs are uncommon, and even when present, they may bear no relationship to the site of the aneurysm. An exception is oculomotor (III) nerve palsy from compression of the nerve ipsilateral to a posterior communicating artery aneurysm. Bilateral extensor plantar responses and abducens (VI) nerve palsy are frequent nonlocalizing signs that result from increased intracranial pressure.

Ruptured AVMs tend to occur within brain tissue and accordingly produce focal neurologic signs, such as hemiparesis, aphasia, or visual field defects.

B. Laboratory Findings

Patients presenting with subarachnoid hemorrhage are investigated first by computed tomography (CT) scanning (Figure 6-5), which confirms the hemorrhage in more than 90% of patients with aneurysmal rupture and can help identify a focal source. The test is most sensitive in the first six hours after bleeding occurs, when sensitivity approaches 100%. Complications, including intracerebral or intraventricular extension of blood, hydrocephalus, and infarction, can also be identified. Aneurysms themselves may not be evident on CT, but most AVMs can be seen after administration of contrast material. Magnetic resonance imaging (MRI) is especially useful for detecting small AVMs in the brainstem, which are poorly seen on CT scan.

In patients with a normal neurologic examination, a normal CT scan within 6 hours of symptom onset is held by many authorities to exclude subarachnoid hemorrhage. CT scans that are technically inadequate or delayed, or that otherwise fail to confirm the diagnosis of subarachnoid hemorrhage, necessitate lumbar puncture (see Chapter 2, Investigative Studies). The CSF in subarachnoid hemorrhage usually has a markedly elevated opening pressure and is grossly bloody, containing 100,000 to >1 million/μL red blood cells. As heme from these cells is degraded, first (by heme oxygenase) to the green pigment, biliverdin, and then (by biliverdin reductase) to the yellow pigment, bilirubin, the supernatant of the centrifuged CSF becomes yellow-tinged (xanthochromic) within 12 hours after hemorrhage. The pigment can be detected spectrophotometrically. White blood cells are initially present in the CSF in the same proportion to red cells as in the peripheral blood. However, chemical meningitis caused by blood in the subarachnoid space may produce a pleocytosis of several thousand white blood cells during the first 48 hours and a reduction in CSF glucose 4 to 8 days after hemorrhage. In the absence of pleocytosis, CSF glucose after subarachnoid hemorrhage is normal. The peripheral white blood cell count is often modestly elevated but rarely exceeds 15,000/μL.

The electrocardiogram (ECG) may reveal a host of abnormalities, including peaked or deeply inverted T waves, a short PR interval, or tall U waves.

Once the diagnosis of subarachnoid hemorrhage is confirmed by CT or lumbar puncture, four-vessel cerebral arteriography is undertaken. Both the carotid and vertebral arteries should be studied to visualize the entire cerebral vascular anatomy, as multiple aneurysms occur in 20% of patients and AVMs are frequently supplied from multiple vessels. Angiography should be performed at the earliest convenient time, and is a prerequisite to the rational planning of surgical treatment. It is therefore not necessary for patients who are not surgical candidates, such as those who are deeply comatose. CT and magnetic resonance angiography do not yet have the resolution needed to replace conventional catheter angiography.

DIFFERENTIAL DIAGNOSIS

The sudden onset of severe headache, with confusion or obtundation, nuchal rigidity, absence of focal neurologic deficits, and bloody spinal fluid is highly specific for subarachnoid hemorrhage.

Other disorders can also produce obtundation and bloody spinal fluid, but are distinguished by additional findings, such as prominent focal neurologic deficits (hypertensive intracerebral hemorrhage) or signs of endocarditis (ruptured mycotic aneurysm) or a presenting history of head trauma.

Traumatic lumbar puncture can be excluded as the cause of bloody CSF by comparing red blood cell counts in the first and last tubes of CSF obtained and by examination of the centrifuged CSF specimen. Blood clears as fluid is removed after a traumatic tap, but not after subarachnoid hemorrhage. Because blood introduced by traumatic lumbar puncture does not have time to undergo enzymatic breakdown to bilirubin, centrifugation of the specimen reveals a colorless supernatant.

Bacterial meningitis is excluded by the presence of blood in the CSF or on CT scan.

COMPLICATIONS & SEQUELAE

A. Recurrence of Hemorrhage

Recurrence of aneurysmal hemorrhage occurs in approximately 20% of patients over 10 to 14 days. It is the major acute complication and roughly doubles the mortality rate. Acute recurrence of hemorrhage from AVM is less common.

B. Intraparenchymal Extension of Hemorrhage

Although hemorrhages from an AVM commonly involve the brain parenchyma, this is far less common with aneurysmal hemorrhage. However, rupture of an aneurysm of the anterior cerebral or middle cerebral artery may direct a jet of blood into the brain with resultant intracerebral hematoma producing hemiparesis, aphasia, and sometimes transtentorial herniation.

C. Arterial Vasospasm

Delayed arterial narrowing (vasospasm) occurs in vessels surrounded by subarachnoid blood and is associated with ischemic neurologic deficits in more than one-third of cases. Clinical ischemia typically does not appear before day 4 after the hemorrhage, peaks at day 7 to 8, and then resolves spontaneously. The diagnosis can be confirmed by transcranial Doppler or cerebral angiography (see Chapter 2, Investigative Studies). The severity of vasospasm is related to the amount of subarachnoid blood, and vasospasm is less common when less blood is present, such as after traumatic subarachnoid hemorrhage or rupture of an AVM. Vasospasm appears to be only one element in the genesis of delayed ischemic neurologic deficits following subarachnoid hemorrhage, as one-third of patients with delayed ischemia clinically do not have demonstrable vasospasm.

D. Acute or Subacute Hydrocephalus

Acute or subacute hydrocephalus may develop during the first three days—or after several weeks—as a result of impaired CSF absorption in the subarachnoid space. Progressive somnolence, nonfocal findings, and impaired upgaze due to downward pressure on the midbrain should suggest the diagnosis.

E. Seizures

Seizures occur in fewer than 10% of cases and only after damage to the cerebral cortex. Decorticate or decerebrate posturing is common acutely and may be mistaken for seizures.

F. Other Complications

Although inappropriate secretion of antidiuretic hormone and resultant diabetes insipidus can occur, they are uncommon.

TREATMENT

A. Medical Treatment

Medical treatment is directed toward preventing elevation of arterial or intracranial pressure that might re-rupture the aneurysm or AVM. Typical measures include absolute bed rest with the head of the bed elevated 15 to 20 degrees, mild sedation, and analgesics for headache (antiplatelet drugs should be avoided). Because patients who are hypertensive on admission have increased mortality, reducing blood pressure (to approximately 160/100 mm Hg) is prudent, but bed rest and mild sedation are often adequate in this regard.

Fever is common and worsens outcome. Induced normothermia is essential (infusion of 4° C NaCl is suggested). Hypotension should be prevented to ensure adequate cerebral perfusion, but intravenous fluids should be isosmotic (normal saline) and should be administered with care, as overhydration can exacerbate cerebral swelling. Hyponatremia is frequently seen and should be managed by oral administration of NaCl, or intravenous 3% normal saline, rather than by fluid restriction.

Following definitive surgical treatment of the ruptured aneurysm and in the absence of other aneurysms, vasospasm can be treated by induced hypertension with phenylephrine or dopamine. The calcium channel antagonist nimodipine, 60 mg orally (or by nasogastric tube) every 4 hours for 21 days, reduces delayed ischemic neurologic deficits in patients with a ruptured aneurysm through neuroprotective mechanisms rather than by a direct effect on vasospasm. Seizures are uncommon after aneurysmal rupture, but the hypertension accompanying an acute seizure increases the risk of re-rupture. Accordingly, prophylactic administration of an anticonvulsant (eg, phenytoin, 300 mg/d) is recommended in the perioperative period and then is discontinued following definite treatment.

B. Surgical Treatment

1. Aneurysm—Definitive surgical therapy of a ruptured aneurysm consists of clipping the neck of the aneurysm or endovascular placement of a coil to induce clotting.

   The neurologic examination is used to grade the patient’s surgical candidacy (Table 6-2). In patients who are fully alert (Hunt and Hess grades I and II) or only mildly confused (grade III), surgery has been shown to improve the clinical outcome. In contrast, stuporous (grade IV) or comatose (grade V) patients do not appear to benefit.

   As rebleeding is maximal within the first 24 hours following aneurysmal rupture, early surgical intervention is indicated. This approach reduces the period at risk for rebleeding and permits aggressive treatment of vasospasm with volume expansion and pharmacologic elevation of blood pressure.

   Treatment of associated unruptured aneurysms is individualized. Surgery is favored by young age, previous rupture, family history of aneurysmal rupture, observed aneurysm growth, and low operative risk. Decreased life expectancy and asymptomatic small (<7-mm diameter) aneurysms favor conservative management.

2. AVM—Surgically accessible AVMs may be removed by en-bloc resection or obliterated by ligation of feeding vessels or by embolization with a local intra-arterial catheter. Because the risk of an early second hemorrhage is much less with AVMs than with aneurysms, surgical treatment can be undertaken electively at a convenient time after the bleeding episode.

PROGNOSIS

The mortality rate from aneurysmal subarachnoid hemorrhage is high. Approximately 20% of patients die before reaching a hospital, 25% die subsequently from the initial hemorrhage or its complications, and 20% die from rebleeding prior to surgical correction. Most deaths occur in the first few days after the hemorrhage.

The probability of survival after aneurysmal rupture is related to the patient’s state of consciousness and the time elapsed since rupture. On day 1, the probability of survival is 60% for symptom-free and 30% for somnolent patients; at 1 month, these groups have survival probabilities of 90% and 60%, respectively. Among survivors of aneurysmal subarachnoid hemorrhage, approximately one-half have permanent brain injury.

Nearly 90% of patients recover after subarachnoid hemorrhage from ruptured AVM. Although recurrent hemorrhage remains a danger, conservative management compares favorably with surgery.

OTHER CEREBROVASCULAR DISORDERS

INTRACEREBRAL HEMORRHAGE

Intracerebral hemorrhage commonly presents with headache, vomiting, altered consciousness, and focal neurologic deficits. Headache in this setting results from compression of pain-sensitive structures by the hematoma. The most common cause of nontraumatic intracerebral hemorrhage is hypertension, but AVMs and bleeding into tumors can present in a similar manner. The CT scan shows a hematoma, which is usually located in the basal ganglia, thalamus, cerebellum, pons, or subcortical white matter. Intracerebral hemorrhage is discussed in more detail in Chapter 13, Stroke.

CEREBRAL ISCHEMIA

Headache occurs at onset of stroke or TIA in one-third of patients and may persist for hours to several days. The association of headache is independent of stroke etiology (thrombotic, embolic, lacunar), stroke severity, or hypertension. Headache is more common with younger age, female gender, cerebellar location, and a history of migraine.

Headaches associated with ischemic stroke are typically mild to moderate in intensity, and nonthrobbing in character. Their location is determined by the pain projection sites of the involved arteries and is most often, but not invariably, ipsilateral to the ischemic hemisphere. Carotid lesions usually produce frontal (trigeminal distribution) pain, whereas posterior fossa strokes usually present with occipital headache. Headache accompanying retinal artery embolism or posterior cerebral artery spasm or occlusion may be erroneously diagnosed as migraine because of the associated visual impairment.

Headache also occurs as part of the cerebral hyperperfusion syndrome after carotid endarterectomy and may be associated with hypertension, focal sensory or motor signs, seizures, and altered consciousness. This syndrome occurs on the second or third postoperative day and typically produces intense throbbing anterior headache on the operated side, often associated with nausea. The cause is thought to be impaired autoregulation of cerebral blood flow.

Headache associated with cerebral infarction may require analgesics for symptomatic relief.

Cerebral ischemia is discussed in more detail in Chapter 13, Stroke.

MENINGITIS OR ENCEPHALITIS

Patients with infection of the meningeal covering of the brain (meningitis) present with a combination of new headache (87%), neck stiffness (83%), fever (77%), and altered mental state (69%). Infection involving brain parenchyma (encephalitis) presents similarly with headache (81%), fever (90%), and altered consciousness (97%), but seizures are frequent (67% in encephalitis while only 5% in meningitis).

Headache is a prominent feature of inflammation of the brain (encephalitis) or its meningeal coverings (meningitis) caused by bacterial, viral, or other infections, as well as granulomatous processes, neoplasms, or chemical irritants. The pain is caused by inflammation of intracranial pain-sensitive structures, including blood vessels at the base of the brain.

The headache is commonly throbbing in character, bilateral, and occipital or nuchal in location. Its severity is increased by sitting upright, moving the head, compressing the jugular vein, or performing other maneuvers (eg, sneezing, coughing) that transiently increase intracranial pressure. Photophobia may be prominent. The headache rarely presents suddenly, developing instead over hours to days.

Neck stiffness and other signs of meningeal irritation (see Figure 1-5) must be sought with care, as they may not be obvious early in the course or in encephalitis. Fever and lethargy or confusion are often, but not always, prominent features.

Mental status abnormalities accompany most cases of bacterial but few cases of aseptic meningitis. Changes may evolve rapidly and vary in severity from mild confusion to coma. Their duration at presentation is less than 24 hours in about 50% of cases of bacterial meningitis. The clinical and laboratory findings in bacterial meningitis are summarized in Table 4-8.

The diagnosis of bacterial meningitis is suggested by a CSF examination that shows an increased white blood cell count (pleocytosis) and low glucose concentration (hypoglycorrhachia) (see Table 4-9). Bacterial, syphilitic, tuberculous, viral, fungal, and parasitic infections may be distinguished by CSF glucose, Gram stain, acid-fast stain, India ink preparation, cryptococcal antibody assays, Venereal Disease Research Laboratory (VDRL), and cultures (see Table 4-5). Treatment of meningitis and encephalitis is discussed in detail in Chapter 4, Confusional States.

BRAIN ABSCESS

Encapsulated pus from contiguous or hematogenous sources produces an expanding mass resulting in headache, change in mental status, focal neurologic defects, and fever. Seizures are the presenting event in 20% to 25% of cases. Headache is a frequent presentation (see Table 3-7) but the classic triad of headache with fever and focal neurologic signs occurs in less than 20%. Progression is rapid with a mean interval of 8.3 days between symptom onset and hospital admission. MRI and CT scanning differentiate abscess from primary or metastatic cancers. Etiology, clinical findings, evaluation, and treatment are discussed in Chapter 3, Coma.

OTHER CAUSES OF ACUTE HEADACHE

SEIZURES

Preictal, ictal, and postictal headaches occur but only the latter are common; they are associated most often with generalized tonic-clonic seizures but also occur following seizures of simple and complex partial phenomenology. Migrainous features (throbbing, nausea and vomiting, photophobia, phonophobia) are common and similar to patients’ non-ictal headaches. It may be important to differentiate these headaches from those of subarachnoid hemorrhage or meningitis. If doubt exists about the cause, lumbar puncture can be undertaken: seizures may produce a mild CSF pleocytosis (up to approximately 10 cells/μL after single seizures or up to approximately 100 cells/μL after status epilepticus), but CSF glucose content is normal.

LUMBAR PUNCTURE

Post-lumbar-puncture headache is diagnosed by a history of a dural puncture (eg, spinal tap, spinal anesthesia) and is characteristically a postural headache, with marked increase in pain in the upright position and relief with recumbency. The pain is typically occipital, comes on within 48 to 72 hours after the procedure, and lasts 1 to 2 days. Nausea and vomiting may occur. Headache is caused by persistent leak of CSF from the spinal subarachnoid space, with resultant traction on pain-sensitive structures at the base of the brain.

The risk of this complication can be reduced by using a small-gauge needle (22 gauge or smaller) for the puncture. Lying flat afterward, for any length of time, does not lessen the risk.

Low-pressure headache syndromes are usually self-limited. When this is not the case, they may respond to the administration of caffeine sodium benzoate, 500 mg intravenously, which can be repeated after 45 minutes if headache persists or recurs upon standing. In persistent cases, the subarachnoid rent can be sealed by injection of autologous blood into the epidural space at the site of the puncture; this requires an experienced anesthesiologist.

Spontaneous intracranial hypotension can produce headache similar in character to that caused by lumbar puncture. T1-weighted, gadolinium-enhanced MRI may show smooth enhancement of the pachymeninges and a “sagging brain” (Figure 6-6); the enhancement may be confused with that associated with meningitis. Low CSF pressure can produce the same MRI picture in the absence of headache. Autologous blood patch injection may produce immediate relief.

HYPERTENSIVE ENCEPHALOPATHY

Headache may be due to a sudden elevation in blood pressure caused by pheochromocytoma, sexual intercourse, the combination of monoamine oxidase inhibitors and tyramine-containing foods such as cheddar cheese, or—the most important cause—malignant hypertension. Blood pressures of 250/150 mm Hg or higher—characteristic of malignant hypertension—produce cerebral edema and displace pain-sensitive structures. The induced pain is described as severe and throbbing. Other signs of diffuse or focal central nervous system dysfunction are also present, such as lethargy, hemiparesis, or focal seizures; on CT or MRI, posterior white matter changes may be seen (see Figure 4-21). Treatment is with antihypertensive drugs (see Chapter 4, Confusional States), but care must be taken to avoid hypotension, which can produce cerebral ischemia and cause stroke.

COITUS

Most coital headaches are benign. Men are more often affected than women. The pain may be either a dull, bilateral pain occurring during sexual excitement or a severe, sudden headache occurring at the time of orgasm, presumably caused by a marked increase in systemic blood pressure. Persistent headache after orgasm—worse in the upright posture—has also been described, is reminiscent of post-lumbar-puncture headache, and is associated with low opening pressures at lumbar puncture. Each of these headaches is benign and subsides over minutes to days.

Patients reporting severe headache in association with orgasm should be evaluated for possible subarachnoid hemorrhage (see earlier discussion). If no hemorrhage is found, prophylactic treatment with indomethacin, 50 to 100 mg orally 30 to 60 minutes prior to intercourse, may be effective.

OPHTHALMIC DISORDERS

Pain about the eye may occur in migraine and cluster headache and is also the presenting feature of iritis and glaucoma. Acute iritis produces extreme eye pain with photophobia. The diagnosis is confirmed by slit lamp examination; acute management involves pharmacologic dilatation of the pupil. Angle-closure glaucoma produces pain within the globe that radiates to the forehead. When it occurs after middle age, such a pain syndrome should prompt diagnostic tonometry.

GIANT CELL ARTERITIS

Giant cell arteritis, also known as temporal arteritis, is a systemic vasculitis that affects medium-sized and large arteries, especially branches of the external carotid artery. It is characterized pathologically by subacute granulomatous inflammation (consisting of lymphocytes, neutrophils, and giant cells). Inflammation of the pain-sensitive arterial wall produces headache, and arterial stenosis leads to ischemia.

Giant cell arteritis affects Caucasians most often, women twice as frequently as men, and is uncommon before 60 years of age. It is frequently associated with malaise, myalgia, weight loss, arthralgia, and fever (polymyalgia rheumatica complex) due to periarticular inflammation. The most common symptom is a new, nonspecific headache, which can be unilateral or bilateral and is often fairly severe and boring in quality. It is characteristically localized to the scalp, especially over the temporal arteries. Scalp tenderness may be especially apparent when lying with the head on a pillow or brushing the hair. Pain or stiffness in the jaw during chewing (jaw claudication) is highly suggestive of giant cell arteritis and is due to arterial ischemia in the muscles of mastication (the tongue may also be affected). Ocular involvement can manifest as transient visual obscurations in one or both eyes lasting minutes to a few hours. Diplopia from ischemia to cranial nerves or extra ocular muscles may be a presenting feature. Anterior ischemic optic neuropathy, characterized by pallid disk edema in one or both eyes, results in permanent visual loss. Involvement of the ophthalmic artery may lead to sudden visual loss, as is discussed in Chapter 7, Neuro-Ophthalmic Disorders.

The erythrocyte sedimentation rate (ESR) is elevated, but not invariably. The mean Westergren ESR is approximately 100 mm/h in giant cell arteritis (range, 29-144 mm/h) and polymyalgia rheumatica (range, 58-160 mm/h); the normal upper limit of the Westergren ESR in elderly patients is reported to be as high as 40 mm/h. Elevated ESR, C-reactive protein level >2.45 mg/dL, and thrombocytosis (>400,000 platelets/μL) each make the diagnosis more likely.

The diagnosis is made by biopsy of an affected temporal artery, which is characteristically thickened, nonpulsatile, dilated, and tender. The arteries may be affected in a patchy manner, and serial sections may be necessary to demonstrate histologic vasculitis.

Possible giant cell arteritis requires prompt evaluation to avoid visual loss, but therapy should not be withheld pending biopsy diagnosis and should be continued despite negative biopsy findings if the diagnosis can be made with confidence on clinical grounds. Initial therapy is with prednisone 60 to 100 mg/d orally. The dose is decreased, usually after 1 to 2 months, depending on the clinical response. Alternatively, treatment can be started with intravenous methylprednisolone (500-1,000 mg every 12 hours for 2 days), with prednisone substituted thereafter. The sedimentation rate returns rapidly toward normal with prednisone therapy and must be maintained within normal limits as the drug dose is tapered over 1 to 2 years. Although dramatic improvement in headache may occur within 2 to 3 days after institution of therapy, associated blindness is usually irreversible.

INTRACRANIAL MASS

The new onset of headache in middle or late life should always raise concern about a mass lesion, such as a brain tumor (Table 6-3), subdural hematoma, or brain abscess (see Chapter 3, Coma), although mass lesions may or may not produce headache, depending on proximity to pain-sensitive intracranial structures or the ventricular system. Only about one-half of patients with brain tumor complain of headache (Table 6-4), although symptoms vary to some extent with tumor type and are more common with metastatic than primary brain tumors.

Headaches associated with brain tumors are most often nonspecific in character, mild to moderate in severity, dull and steady in nature, and intermittent. The pain is characteristically bifrontal, worse ipsilaterally, and aggravated by a change in position or by maneuvers that increase intracranial pressure, such as coughing, sneezing, and straining at stool. Headache is worse with bending over. Both tension or migraine type features may be found. Evidence of lateralized features on exam are most suggestive of a mass. The classic brain tumor headache (severe, early morning, and associated with nausea and vomiting) is uncommon; nausea and vomiting occur in less than half of brain tumor patients. The occurrence of headaches in brain tumor is proportional to tumor size and midline shift. Subdural hematoma frequently presents with conspicuous headache, because its large size increases the likelihood of impinging upon pain-sensitive structures.

An uncommon type of headache that suggests brain tumor is characterized by a sudden onset of severe pain that reaches maximal intensity within seconds, persists for minutes to hours, and subsides rapidly. This may be associated with altered consciousness or “drop attacks.” Although classically associated with third ventricular colloid cysts, these paroxysmal headaches can be produced by tumors at many different intracranial sites. Trigeminal autonomic cephalalgia type headaches (see below) may be the presenting feature of pituitary tumors.

Suspicion of an intracranial mass lesion demands prompt evaluation by CT scan or MRI. Brain tumor is excluded by a normal contrast-enhanced brain MRI scan. Tumor treatment depends on the histologic type (benign or malignant, primary or metastatic, pathologic grade), but may include surgical excision, radiation, and chemotherapy. Prognosis also varies with tumor characteristics, as well as age, biomarkers, and gene polymorphisms.

IDIOPATHIC INTRACRANIAL HYPERTENSION

Idiopathic intracranial hypertension (pseudotumor cerebri) is the result of a diffuse increase in intracranial pressure that can cause headache of diffuse but variable character, papilledema, pulsatile tinnitus, visual loss, and diplopia (from abducens [VI] nerve palsy). Impaired CSF absorption due to venous outflow obstruction may be involved in pathogenesis. Intracranial hypertension can also be symptomatic of a variety of disorders (Table 6-5), but these are less common than the idiopathic form.

Women are affected much more commonly than men, with a peak incidence in the third decade. Most patients are obese. Diffuse headache is almost always a presenting symptom. The headaches are daily in occurrence, pulsatile or pressing, moderate in intensity, and aggravated by coughing or straining. Transient (seconds-long) visual obscurations and visual blurring also occur in most cases. Visual acuity is normal in most patients at presentation, but moderate to severe papilledema is seen in almost all. Visual loss can develop from increased intracranial pressure, which leads to optic (II) nerve atrophy. Like visual loss from glaucoma, that due to idiopathic intracranial hypertension is characterized by gradually constricting visual fields with late loss of central acuity. Associated pulsatile tinnitus is common.

Symptoms of idiopathic intracranial hypertension are generally self-limited over several months and papilledema may disappear, but CSF pressure remains elevated for years, and recurrent symptomatic episodes occur in 10%. Using MRI or CT brain scanning, lumbar puncture, and laboratory studies, idiopathic intracranial hypertension must be differentiated from intracerebral mass lesions and from the disorders listed in Table 6-5. Imaging studies may show small (“slit-like”) ventricles and demonstrate an empty sella turcica in 70% of instances. The optic nerve sheath is characteristically dilated, and the back of the globe is flattened. Elevated intracranial pressure (CSF opening pressure >250 mm H₂O) is documented by lumbar puncture, and removal of 20 to 40 mL of CSF may transiently relieve headache. Cells, glucose, and protein content of the CSF are normal. However, it should be noted that obese individuals without idiopathic intracranial hypertension may have opening pressures as high as 250 mm H₂O.

If other causes (see Table 6-5) are identified, specific treatment should be given. Cerebral venous thrombosis must be excluded by imaging. Treatment of idiopathic cases is with acetazolamide (1000-1250 mg/d); topiramate may also be effective for headache treatment. Corticosteroids are effective, but have untoward side effects, and papilledema tends to rebound when they are discontinued. Obese patients should be encouraged to lose weight. In cases refractory to medical treatment, optic nerve sheath fenestration or lumboperitoneal or ventriculoperitoneal shunting may be needed to preserve vision and decrease headache.

TRIGEMINAL NEURALGIA

Trigeminal neuralgia (tic douloureux) is a facial pain syndrome that develops in middle to late life and is more common in women than men.

Pain is unilateral and typically confined to the area supplied by the second (V2) and third (V3) divisions of the trigeminal (V) nerve (Figure 6-7). Involvement of the first division or bilateral disease occurs in less than 5% of cases. Pain occurs as lightning-like, momentary (>1 second to approximately 2 minutes) jabs of excruciating pain that spontaneously abate, and attacks are stereotypic in a given patient. Occurrence during sleep is uncommon. Pain-free intervals may last for minutes to weeks, but long-term spontaneous remission is rare. Stimulation of trigger zones about the cheek, nose, or mouth by touch, cold, wind, talking, or chewing can precipitate the pain. In classical trigeminal neuralgia, physical examination discloses no abnormalities; trigeminal sensory deficits or abnormal trigeminal (eg, corneal or jaw jerk) reflexes exclude an idiopathic diagnosis. Rarely, similar pain may occur in multiple sclerosis or with brainstem tumors, which should be considered in young patients, in those with ophthalmic division pain, and in all patients who show neurologic abnormalities on examination or who experience bilateral symptoms.

CT scan, conventional MRI, and arteriography are normal. Although high-resolution MRI techniques may show microvascular nerve compression, no standard technique has been identified to document symptomatic vascular compression.

Treatment with carbamazepine 400 to 1200 mg/d orally in three divided doses produces remission of pain within 24 hours in a high percentage of cases. Rarely, blood dyscrasia occurs as an adverse reaction to carbamazepine. Oxcarbazepine (600-1,800 mg/d in two divided doses) appears equally effective, without risk of blood dyscrasia. Intravenous administration of phenytoin 250 mg will abort an acute attack, and phenytoin 200 to 400 mg/d orally may be effective alone or in combination with carbamazepine if a second drug is necessary. Lamotrigine (400 mg/d) or baclofen (10 mg three times daily to 20 mg four times daily) can be used in refractory cases. Posterior fossa microvascular decompression surgery is used in patients who fail or cease to respond to drugs. The superior cerebellar artery is the most commonly implicated.

GLOSSOPHARYNGEAL NEURALGIA

Glossopharyngeal neuralgia is a rare syndrome mainly characterized by unilateral pain localized to the oropharynx, tonsillar pillars, base of the tongue, or auditory meatus. Pain may be paroxysmal, resembling that described for trigeminal neuralgia, or more continuous and burning or aching in quality. Rarely, cardiac syncope due to bradyarrhythmia (Chapter 12, Seizures & Syncope) accompanies the pain. Trigger areas are usually around the tonsillar pillars, so symptoms are initiated by swallowing or talking. Paroxysms of pain can occur many times daily.

Women are affected more frequently than men. Symptoms begin at a somewhat younger age than in trigeminal neuralgia. The diagnosis is established by the history and by reproducing pain through stimulation of peritonsillar trigger zones. There are no abnormal neurologic signs. Bilateral symptoms, abnormal signs, or other atypical features should prompt a search for disorders that can mimic glossopharyngeal neuralgia, such as multiple sclerosis, cerebellopontine angle tumor, and nasopharyngeal carcinoma.

As in trigeminal neuralgia, conventional imaging techniques show no abnormalities, but high-resolution MRI techniques may reveal microvascular or space occupying lesions compressing the glossopharyngeal (IX) nerve.

Carbamazepine or phenytoin (as described earlier for trigeminal neuralgia) usually produces dramatic relief; microvascular decompression has been used in drug-resistant cases.

HERPETIC & POSTHERPETIC NEURALGIA

Varicella-zoster virus infection produces a febrile illness with a disseminated vesicular rash (chickenpox). After the primary infection, the virus remains dormant in sensory ganglia but may reactivate, particularly with age or immunosuppression, resulting in a unilateral vesicular eruption termed shingles. These eruptions, which occur in a dermatomal distribution (most commonly thoracic, 50%; ophthalmic distribution of the trigeminal nerve, 25%), are associated with sharp, lancinating, localized radicular pain with dysesthesia. In patients over 50, pain may persist beyond six weeks. This constitutes postherpetic neuralgia.

The syndrome does not occur before age 50 years and becomes increasingly common with advancing age, in immunocompromised patients, and in those with leukemia or lymphoma.

Postherpetic neuralgia is characterized by constant, severe, stabbing or burning, dysesthetic pain. In the head, the first division (V1) of the trigeminal (V) nerve is most commonly affected, so pain localized to the forehead on one side is usually the presenting feature (Figure 6-8). Scarring, resulting from healing of the vesicular rash, may be present in the distribution of pain. Careful testing of the painful area reveals decreased cutaneous sensitivity to pinprick. The other major complication of herpes zoster in the trigeminal distribution is decreased corneal sensation with impaired blink reflex, which can lead to corneal abrasion, scarring, and ultimately loss of vision.

The intensity and duration of the cutaneous eruption and the acute pain of herpes zoster can be reduced by acute treatment for 7 to 10 days with acyclovir (800 mg five times daily), famciclovir, or valacyclovir, but these treatments have not been shown to lessen the likelihood of postherpetic neuralgia, although the duration of the postherpetic pain may be attenuated. Corticosteroids (60 mg/d prednisone, orally for 2 weeks, with rapid tapering) taken during the acute herpetic eruption may reduce acute herpetic pain, but not the development of postherpetic neuralgia.

Once the postherpetic pain syndrome is established, the most useful treatment has been tricyclic antidepressants such as amitriptyline, 25 to 150 mg/d orally, which are thought to act directly on central nervous system pain-integration pathways, rather than via an antidepressant effect; nortriptyline or desipramine may be better tolerated. Tricyclic antidepressant drugs may be more effective when combined with a phenothiazine (perphenazine). The anticonvulsants gabapentin (1,800-3,600 mg/d) and pregabalin (600 mg/d) have shown some benefit.

Lidocaine-prilocaine (2.5% cream) or lidocaine (5% gel or cutaneous patch) is an effective topical therapy. Topical capsaicin (0.075% cream or 8% patch) can also be helpful, but may cause local skin irritation. Capsaicin acts as a transient receptor potential cation channel (TRPV1) antagonist to deplete pain-mediating peptides (substance P, calcitonin gene-related peptide) from peripheral sensory neurons. In otherwise intractable cases, weekly intrathecal administration of methylprednisolone may reduce pain.

PERSISTENT IDIOPATHIC FACIAL PAIN

Constant, boring, mainly unilateral, lower facial pain for which no cause can be found is referred to as persistent idiopathic or atypical facial pain. Unlike trigeminal neuralgia, it is not confined to the trigeminal nerve distribution and is not paroxysmal. Neurologic and neuroradiographic examinations are normal. This idiopathic disorder must be distinguished from similar pain syndromes related to nasopharyngeal carcinoma, intracranial extension of squamous cell carcinoma of the face, or infection at the site of a tooth extraction. Treatment is with amitriptyline 20 to 250 mg/d orally, alone or in combination with phenelzine 30 to 75 mg/d orally. Phenytoin can be an effective alternative, especially if a tricyclic antidepressant is poorly tolerated.

MIGRAINE

Migraine is common (prevalence 12%) and is manifested by recurrent headache. The migraine attack begins with visual or other neurologic (usually sensory) symptoms in approximately 15% to 30% of patients (migraine with aura, or classic migraine), followed by the headache phase. In most cases, however, no aura occurs (migraine without aura, or common migraine). Before puberty, males and females are equally affected. After puberty, two-thirds to three-quarters of migraine cases occur in women. Onset is early in life—approximately 25% begin during the first decade, 55% by age 20, and more than 90% before age 40.

GENETICS

Although candidate genes remain uncertain, a family history of migraine in at least one first-degree relative is present in most cases, and twin studies demonstrate the involvement of both inheritance and environmental factors. For those with affected relatives, the risk of migraine is enhanced three times. Autosomal dominant inheritance occurs in several well-recognized migraine syndromes, including familial hemiplegic migraine and cerebral autosomal dominant arteriopathy with subcortical infarcts (CADASIL). Hemiplegic migraine also occurs in families. Mutations in genes encoding membrane ion channels have been implicated in this syndrome (Table 6-6).

STRUCTURAL FEATURES

Migraine is associated with an increase in MRI-detected white matter lesions, infarct-like lesions, and volumetric changes in cerebral gray and white matter. Women may be affected more frequently, as may patients with aura. No clear association with headache frequency is firmly established. The clinical significance of these MRI finding is uncertain; cognitive consequences have not been found.

PRECIPITATING FACTORS

In many patients, migraine attacks are heralded by prodromal fatigue or cognitive, affective, or gastrointestinal symptoms, which can last for up to 1 day. The basis for this premonitory phase is poorly understood, but it may reflect altered hypothalamic or brainstem functions. Migraine attacks can be precipitated by certain foods (tyramine-containing cheeses; meat, such as hot dogs or bacon, with nitrite preservatives; chocolate containing phenylethylamine but not chocolate alone) and by food additives such as monosodium glutamate, a commonly used flavor enhancer. Lifestyle issues such as fasting, emotion, menses, drugs (especially oral contraceptive agents and vasodilators such as nitroglycerin), weather changes, sleep disturbances, and bright lights may also trigger attacks.

PATHOGENESIS

Based on the efficacy of vasoconstrictive ergot alkaloids (eg, ergotamine) in aborting the acute migraine attack and of vasodilators such as amyl nitrite in abolishing the migraine aura, intracranial vasoconstriction and extracranial vasodilation were long held to be the respective causes of the aura and headache phases of migraine. However, more recent studies support cortical spreading depression as responsible for both the aura and headache (Figure 6-9). Resultant sensitization (increased neuronal responsiveness to painful and non-painful stimuli) results in many of the migrainous symptoms, including cutaneous allodynia (pain produced from an innocuous stimulus).

Functional MRI during migraine headache demonstrates cerebral blood flow changes in the dorsal pons and the cingulate, visual, and auditory cortices. These signals propagate with characteristics similar to cortical spreading depression. At the onset of the aura phase (occurring in up to 30% of patients), a decrease in cerebral blood flow in the occipital cortex spreads anteriorly across the cortex according to cytoarchitectural rather than vascular boundaries (see Figure 6-9). In this respect, and in its rate of propagation (2-5 mm/minute), it resembles the phenomenon of spreading depression, in which a slow wave of neuronal and glial depolarization decreases blood flow and inhibits neuronal activity in its wake. However, the areas of decreased blood flow do not correspond to the cortical regions responsible for a particular aura, the extent of decrease is insufficient to cause ischemic symptoms, blood flow may remain depressed after aura symptoms have resolved and headache has begun, and headache may begin during the aural phase as well. Inhibiting spreading depression can prevent the migraine aura (but not the subsequent headache). These findings suggest that changes in neuronal activity, rather than ischemia, produce the aura. However, what initiates spreading depression is poorly understood.

Two principal mechanisms have been proposed to explain the headache phase. According to one theory, pain is triggered peripherally in primary sensory trigeminal neurons innervating the meninges and blood vessels, perhaps as a result of sterile inflammation (see Figure 6-9). These neurons project to the nucleus caudalis in the brainstem, and from there to the periaqueductal gray, sensory thalamic nuclei, and somatosensory cortex. Another theory holds that a primary disturbance of central pain pathways produces sensitization, so that normally innocuous sensory input is misinterpreted as signaling pain, a phenomenon termed allodynia.

CLINICAL FINDINGS

A. Migraine With Aura (Classic Migraine)

In 30% of migraine patients, headache is preceded by transient neurologic symptoms (aura) lasting less than one hour. Auras may be visual, sensory (affecting limb, face, or tongue), vertebrobasilar, or motor. The most common auras are visual alterations, particularly hemianopic field defects and scotomas (blind spots) and scintillations (flickerings) that enlarge and spread peripherally (Figure 6-10). A throbbing unilateral headache ensues (Figure 6-11). The frequency of headache varies, but more than 50% of patients experience no more than one attack per week. The duration of episodes is greater than 2 hours and less than 1 day in most patients. Remissions are common during the second and third trimesters of pregnancy and after menopause.

Although hemicranial pain is a hallmark of classic migraine, headaches can also be bilateral or occipital in location—characteristics commonly attributed to tension-type headache, which likely represents trigeminal and upper cervical afferent pathways converging in the brainstem.

During the headache, prominent associated symptoms include nausea, vomiting, photophobia, phonophobia, irritability, osmophobia, and lassitude. Vasomotor and autonomic symptoms are also common. Lightheadedness, vertigo, impaired hearing, diplopia, dysarthria, tinnitus, ataxia, or altered consciousness may occur with basilar migraine. Migrainous aura occasionally produces neurologic deficits that persist into or beyond the pain phase (eg, hemiplegic migraine) and may rarely cause stroke. Motor manifestations of migraine can be distinguished from stroke by both the gradual onset (“migrainous march”) and spontaneous resolution of symptoms.

Especially after 50 years of age, the aura may occur without headache (late-life migraine equivalents). Symptoms include visual disturbance, hemiparesis, hemisensory loss, dysarthria, or aphasia and usually last for 15 to 60 minutes (the gradual, non-stroke-like, “migrainous march” of sensory–motor symptoms is diagnostically helpful).

Other migraine subtypes include retinal migraine (headache with monocular scotoma), vestibular migraine, and menstrual migraine.

B. Migraine Without Aura (Common Migraine)

Migraine without aura is much more common than migraine with aura and produces headache that is most often unilateral in location, pulsating in quality, and moderate to severe in intensity. Nausea, vomiting, photophobia, and phonophobia are common. As the pain persists, associated cervical muscle contraction can compound the symptoms. Scalp tenderness is often present during the episode. If untreated, headache usually persists for 4 to 72 hours and is occasionally terminated by vomiting. In both common and classic migraine, compressing the ipsilateral carotid or superficial temporal artery during headache may reduce its severity.

C. Chronic (Transformed) Migraine and Medication Overuse Headache

Episodic migraine can change its clinical features over months to years, evolving into a chronic headache syndrome with nearly daily pain. The headache often loses its classic migrainous features. Obesity, prior headache frequency, and caffeine use are associated risk factors. A common subgroup of chronic migraine is that of headache from medication overuse.

Overuse of medications used to treat migraine or other forms of headache can lead to a chronic daily headache. Most patients have migraine as their underlying problem and have overused simple analgesics or triptans, but patients with other types of headache and those using other classes of drugs are also susceptible. Most patients are women. Headache is characteristically present at least 15 days per month for at least 3 months. Treatment involves tapering or withdrawal of the offending medications and beginning prophylactic therapy (see Table 6-8). Corticosteroids may be useful for “bridge therapy” to attenuate exacerbation of headache by drug withdrawal.

THE MIGRAINE POSTDROME

Following cessation of a migraine episode, migraine symptoms may reoccur with sudden head movement. A feeling of exhaustion (or rarely elation/euphoria) also may also be experienced.

TREATMENT

Tables 6-7 and 6-8 summarize treatment options in migraine. Addressing lifestyle issues pertaining to regularity of habits can be helpful (see precipitating factors). Pharmacologic treatment can be divided into measures used to abort attacks in progress (abortive) and to prevent future episodes (prophylactic).

Acute migraine attacks often respond to simple analgesics or, if these are ineffective, to migraine-specific therapies: serotonin 5-HT_1B/D receptor agonists (triptans) or ergot alkaloids (eg, dihydroergotamine). A new class of antimigraine drugs—calcitonin gene-related peptide receptor antagonists (eg, telcagepant, olcegepant, and CGRP monoclonal antibodies)—may prove to be useful for this purpose. Drugs for acute (abortive) treatment (Table 6-7) must be taken at the onset of symptoms to be maximally effective. Rapidly absorbed parenteral formulations are superior to oral preparations. Nausea, a prominent feature of migraine, is also a common side effect of some antimigraine drugs, so that administration by other than the oral route or concomitant administration of an antiemetic (Table 6-7) may be necessary. Ergot alkaloids and triptans are felt by many to be contraindicated in patients with hypertension or other cardiovascular disease but the mechanism of action of these drugs is not via vasoconstriction.

Prophylactic treatment should be used in patients with two or more headaches per week or those in whom abortive treatment is inadequate. Tricyclic antidepressants, β-blockers, anticonvulsants, and calcium channel blockers can be tried in that order, unless concurrent illnesses or medications dictate differently (see Table 6-8). Chronic migraine (greater than 15 days/month), unresponsive to pharmacotherapeutics, has been treated, in specialized centers, with botulinum toxin injections.

For migraine during pregnancy, women can expect a decrease in headache frequency in the second and third trimesters and a return to prepregnancy frequency after delivery. For acute headache treatment, acetaminophen is safe for mild to moderate pain. More severe headaches can be treated with narcotic analgesics; sumatriptan appears safe even in the first trimester. Prochlorperazine (oral or suppository) is safe for both nausea and headache. See Table 6-9 for recommended agents. Other antimigraine drugs may be teratogenic or cause complications in pregnancy.

CLUSTER HEADACHE & TRIGEMINAL AUTONOMIC CEPHALALGIAS (TACs)

CLINICAL FINDINGS

Cluster headache presents as repetitive episodes (clusters) of brief (15-180 minutes), very severe, unilateral, constant, nonthrobbing headaches. Episodes may be precipitated by alcohol or vasodilating drugs, especially if used during a cluster siege. The headache may begin as a burning sensation over the lateral aspect of the nose or as pressure behind the eye (Figure 6-12). The headache is associated with ipsilateral conjunctival injection, lacrimation, nasal stuffiness, or Horner syndrome (Figure 6-13).

Cluster headaches are always unilateral and usually recur on the same side in a given patient. They occur most often at night, awakening the patient from sleep; patients may pace restlessly during attacks. Headaches are recurrent (daily to multiple times daily), occurring often at nearly the same time of day (circadian periodicity) and for a cluster period of weeks to a few months; seasonal recurrences also occur. Between clusters, the patient may be free from headaches for months or years. The cause is unknown, but functional MRI during attacks has shown posterior inferior hypothalamic gray matter activation homolateral to the headache.

Cluster headache occurs much more frequently in men than in women (3:1) and typically begins at a somewhat later age than migraine (mean onset at 25 years). There is occasionally a family history.

TREATMENT

At the onset of a headache cluster, treatment involves measures both to abort the acute attack and to prevent subsequent ones.

A. Acute Treatment

Prompt relief of pain is achieved by inhalation of 100% oxygen (7-12 L/min for 15-20 minutes) or subcutaneous administration of sumatriptan (6 mg, repeated once per attack if necessary) (see Table 6-7). Alternative abortive treatments include intranasal sumatriptan, zolmitriptan, or lidocaine; subcutaneous octreotide; intravenous, intramuscular, subcutaneous, or intranasal dihydroergotamine; and oral zolmitriptan.

B. Maintenance Prophylaxis

Several drugs used in the treatment of migraine (see Table 6-8) are also useful for preventing recurrent symptoms during an active bout of cluster headache (maintenance prophylaxis). The most widely used drug is verapamil (80 mg three times daily or sustained-release 240 mg/d; doses of 720 mg/d may be required). Anticonvulsants such as valproic acid (500-2,000 mg/d), gabapentin (300-3,600 mg/d), and topiramate (50-200 mg/d) (often used in combination with verapamil) are second-line agents. Melatonin (10 mg/d) can also be helpful. Botulinum toxin is not effective. Drugs used for maintenance prophylaxis are discontinued at the end of the cluster.

C. Transitional Prophylaxis

Administration of prednisone at the beginning of a cluster cycle can be abortive, when given as 40 to 80 mg/d orally for 1 week, and then discontinued by tapering the dose over the following week. Intravenous methylprednisolone or dihydroergotamine may be useful as well.

D. Cluster Headache Variants

Chronic rather than episodic cluster headaches may occur. Hypnic headache, a bilateral nocturnal syndrome, lacks the autonomic components of cluster headache and occurs in the elderly. Suppressive therapy includes lithium or indomethacin. Paroxysmal hemicrania headaches occur in groups with daily attacks of 2-3 minutes and respond dramatically to indomethacin 25 to 50 mg three times daily.

Hemicrania continua describes continuous pain with exacerbations of hours to days. It is also indomethacin responsive. A syndrome of hemicrania continua (continual pain with exacerbations) has been described as a presenting feature of pituitary tumors. Further, short-lasting, unilateral syndromes with conjunctival injection and tearing occur (attacks of 1-600 seconds); they respond to lamotrigine or topiramate.

E. Invasive Treatment

Invasive treatments are reserved for patients who fail to respond to medications; these include greater occipital nerve block, radiofrequency trigeminal ganglion ablation, or trigeminal rhizotomy.

TENSION-TYPE HEADACHE

Tension-type headache is the term used to describe chronic or recurrent headache of unapparent cause that lacks features of migraine or other headache syndromes. The underlying pathophysiologic mechanism is unknown, and “tension” is unlikely to be primarily responsible. Contraction of neck and scalp muscles has not been demonstrated by electromyography and, if present, is probably a secondary phenomenon.

In its classic form (Figure 6-14), tension-type headache is a chronic disorder that begins after age 20 years. It is characterized by attacks of nonthrobbing, bilateral occipital head pain that is not associated with nausea, vomiting, or prodromal visual disturbance. Headache duration is from hours to days. The pain is sometimes likened to a tight band around the head.

Women are more commonly affected than men. Although tension-type headache and migraine have been traditionally considered distinct disorders, many patients have headaches that exhibit features of both. Thus, occasional patients who are classified as having tension-type headaches experience throbbing headaches, unilateral head pain, or nausea with attacks. In consequence, it may be more accurate to view tension-type headache and migraine as representing opposite poles of a single clinical spectrum.

Drugs used in the treatment of tension-type headache include some of the same agents used for migraine (see Tables 6-7 and 6-8). Acute attacks may respond to aspirin, other nonsteroidal anti-inflammatory drugs, or acetaminophen. Tension-type headache in migraineurs may respond to triptans. For prophylactic treatment, amitriptyline, nortriptyline, or imipramine is often effective. Trials of botulinum toxin mostly show that it is unhelpful. Massage, physical therapy, and relaxation techniques can provide additional benefit in selected cases.

ICEPICK-LIKE PAIN

Very brief, sharp, severe pain located in the scalp, occurring mainly in the V1 trigeminal distribution (Figure 6-1), is called “icepick-like pain.” Women are more commonly affected. Paroxysms of pain are single or repetitive or occur in clusters, either at a single point or scattered over the scalp. Pain is experienced as an electric-like jab that reaches maximal intensity in less than 1 second, resolves rapidly, and is severe enough to cause involuntary flinching. Icepick-like pain is more common in those with migraine or cluster headache, but may occur in individuals who are otherwise headache-free. Patients frequently seek medical attention because of the intensity of the pain. If the bouts of pain are recurrent, treatment may be indicated. The syndrome responds to indomethacin (25-50 mg three times daily); gabapentin (400 mg twice daily) and melatonin (3-12 mg at bedtime) have also been reported as effective. Lancinating exacerbations of highly localized regional (mainly parietal) oval areas of pain are termed nummular headaches. Treatment is with gabapentin or indomethacin.

CERVICAL SPINE DISEASE

Injury or degenerative disease processes involving the upper neck can produce pain in the occiput or orbital regions. The most important source of discomfort is irritation of the second cervical (C2) nerve root. Disk disease or abnormalities of the articular processes affecting the lower cervical spine refer pain to the ipsilateral arm or shoulder, not to the head, although cervical muscle spasm may occur. Acute pain of cervical origin is treated with immobilization of the neck (eg, with a soft collar) and analgesic or anti-inflammatory drugs.

SINUSITIS

Acute sinusitis can produce pain and tenderness localized to the affected frontal or maxillary sinuses. Inflammation in the ethmoidal or sphenoidal sinuses produces a deep midline pain behind the nose. Sinusitis pain is increased by bending forward and by coughing or sneezing. Percussion over the frontal or maxillary area produces tenderness and accentuation of pain.

Sinusitis is treated with vasoconstrictor nose drops (eg, phenylephrine, 0.25%, instilled every 2-3 hours), antihistamines, and antibiotics. In refractory cases, surgical sinus drainage may be necessary.

Patients who complain of chronic “sinus” headache rarely have recurrent inflammation of the sinuses; they are much more likely to have a primary headache syndrome.

DENTAL DISEASE

Temporomandibular joint dysfunction is a poorly defined syndrome characterized by preauricular facial pain, limitation of jaw movement, tenderness of the muscles of mastication, and “clicking” of the jaw with movement. Symptoms are often associated with malocclusion, bruxism, or clenching of the teeth and may result from spasm of the masticatory muscles. Some patients benefit from local application of heat, jaw exercises, nocturnal use of a bite guard, or nonsteroidal anti-inflammatory drugs.

Infected tooth extraction sites can also give rise to pain, which is characteristically constant, unilateral, and aching or burning in character. Acute dental pain rarely crosses the midline. Although radiologic studies may be normal, injection of a local anesthetic at the extraction site relieves the symptoms. Treatment is with jawbone curettage and antibiotics.