OVERVIEW

Headache is one of the most common medical complaints; up to 90% of the general population has experienced tension-type headache, for example.¹ Among pain conditions, recurrent headache disorders account for the bulk of lost work time and disability.² Many headaches are self-treated, but headache is still a leading cause of emergency department (ED) and physician visits. Most people with recurrent troublesome headaches have tension-type, migraine, or cluster headaches. These are referred to as “primary headaches” in the widely used International Classification of Headache Disorders—II (Table 77-1).³ It is vitally important, however, that clinicians rule out life-threatening causes of headaches.

Table 77-1 International Headache Society Classification of Headache Disorders—II

EPIDEMIOLOGY AND RISK FACTORS

The lifetime prevalence of the most common of headaches, the tension-type headache, is estimated at 30% to 80%,⁴ though most everyone has had this type of headache at one time or another.

Over 28 million Americans have migraines; half remain undiagnosed.⁵ Approximately 20% of women suffer from migraines, as opposed to 6% of men.⁶ Worldwide prevalence studies roughly mirror the United States data. Prevalence peaks during the average individual’s most productive years, from ages 25 to 55. The World Health Organization con-siders severe migraine to be among the four most disabling human conditions along with acute psychosis, dementia, and quadriplegia.

Chronic daily headache, a collective term that refers to primary headaches that occur more than 14 (or more than 15 as in the International Headache Society [IHS] classification) days per month for at least 3 months, shows a stable worldwide prevalence of about 4%,⁷ though there may be significant variation in the individuals who make up this group. Frequently, chronic daily headache may develop from preexisting migraines or tension-type headaches. Less commonly, the pattern may develop de novo (Table 77-2).⁸ Risk factors for chronic daily headache include female sex, low education level, medication overuse, a history of head or neck trauma, and cigarette smoking.⁷

Table 77-2 Conditions Associated with Chronic Daily Headaches

Secondary headaches carry a prevalence related to the underlying condition. (see Clinical Features, Diagnosis and Treatment, later in this chapter).

GENETICS

Multiple studies indicate a genetic influence in many of the primary headaches. The inheritance in migraine is likely multifactorial, and the odds ratio may increase proportionate to the severity of migraine in the proband but does not seem to relate to the type of headache. Anticipation is noted over generations, with a tendency toward earlier age of onset. Notwithstanding, less than 50% of migraine cases are thought to exhibit genetic influences,⁹ thus this is likely also a common sporadic condition.

In patients with a rare form of migraine, familial hemiplegic migraine, the responsible genetic defect results in calcium channel dysfunction (channelopathy) that is thought to explain the migraine symptoms in these patients. Familial hemiplegic migraine has been associated with two mutations. CACNA1A gene on chromosome 19 is affected in FHM1 and ATP1A2 on chromosome 1 is affected in FHM2.¹⁰ Though the first “migraine gene” has been uncovered and thus is a model for studying the genetic basis of migraine, translation of this information to the more common forms of migraine is still in process.

In tension-type headache, the high prevalence confounds the detection of a genetic influence. Nonetheless, studies of several large populations do suggest a complex multifactorial mode of inheritance in favor of a sporadic condition. A genetic influence is likely in cluster headache as well, though the exact mode is unclear, possibly an autosomal dominant mode with reduced penetrance or an autosomal recessive pattern.¹¹

PATHOPHYSIOLOGY

Except for the posterior fossa, which is supplied by the high cervical nerve roots, most head pain is mediated through the first division of the trigeminal nerve.¹² Nociceptive C and A-delta fibers innervate the skin, periosteum, large vessels (arteries, veins, and sinuses) and meninges¹³ (Figure 77-1). Thus, pain may arise from any of these areas, yet not from the substance of the brain, which contains no nociceptive fibers. The cervical and trigeminal nociceptive information is distributed to the “trigeminocervical complex,” a large ipsilateral nuclear group spanning the trigeminal nucleus caudalis (rostrally) to the high cervical dorsal horn cells (caudally). Second-order pathways then cross from there and terminate in the thalamus; third-order pathways then bring the information to the cortex. Descending endogenous inhibitory pain systems may influence the incoming signals at the juncture between the first- and second-order neurons. This simplified scheme may mediate most, if not all, head pain no matter what the cause.

Figure 77-1 Pain pathway showing the innervation of the meninges and cerebral vessels by the V1 division of the trigeminal nerve. The impulse moves down the trigeminal nerve to the trigeminocervical complex. Then the pathway ascends to the thalamus, before going on to the cortex—amygdala, sensory association, and primary sensory area for the head.

As to the cause of migraine specifically, dysfunction in these brainstem systems, possibly genetically determined, is one theory of migraine generation. Also, cortical spreading depression (CSD), originally described by Leao and now thought to be the mechanism of the aura in migraine, may result in local ionic and chemical changes that might sensitize perivascular trigeminal fibers that set off a cascade of changes to produce the clinical symptomatology of migraine with aura by way of the simplified scheme above.⁹ Included in this process, trigeminal neural impulses may subsequently “feed back” through various routes to the meninges leading to local release of neuropeptides (e.g., CGRP, substance P, and VIP) that can amplify and sustain the headache cascade, perhaps influencing the development of cutaneous skin hypersensitivity (allodynia) seen in some patients and perhaps also setting the stage for the development of a chronic headache pattern. Stimulation of nearby brainstem nuclei by this cascade may also explain some of the associated constitutional symptoms that are commonly seen in migraine.

Tension-type headache may result from persistent peripheral nociceptive hyper-stimulation and may share many of the pathophysiological features of migraine. Whether tension-type headache is ultimately viewed as a variation of migraine or as a separate pathological condition remains unsettled. Recent information suggests a central, possibly hypothalamic, cause for cluster headaches with important peripheral trigeminovascular activation as well.

The pathogenesis of a secondary headache depends on the etiology of each particular headache and will be discussed with descriptions of each condition in Clinical Features, Diagnosis and Treatment, later in this chapter.

DIFFERENTIAL DIAGNOSIS

While most patients with dangerous headaches are treated in the ED, the psychiatrist who is familiar with the presentation of rare headache syndromes may be a life-saver. A host of conditions need to be considered when an individual complains of a headache. Differentiating among all potential causes of headaches can be daunting. The task can be made less difficult by ruling out dangerous causes of headaches (Table 77-3). Once this has been done the clinician can match the headache history to the headache syndrome.

Table 77-3 Clues to Dangerous Headaches

AVM, Arteriovenous malformation; ICP, intracranial pressure; LP, lumbar puncture; N/V, nausea and vomiting; SAH, subarachnoid hemorrhage.

Because the clinical features vary for the different causes of headache, taking the headache history is the most crucial aspect of the workup (Table 77-4).⁶ Identification of the life-threatening causes of headache can usually be done with a thorough history. Elucidation of such features of the pain as timing (e.g., acute or chronic), onset (e.g., sudden or insidious), duration, severity, location (e.g., unilateral, bilateral, including the neck or eyes), associated symptoms (e.g., visual changes, motor symptoms, nausea, diaphoresis, and anxiety), body position (e.g., after standing up or lying down), and setting (e.g., during sleep, at work, or after exercise) is important. The effects of medication, meals (including specific foods [such as chocolate]), substances (such as caffeine and alcohol), sleep, and exercise also offer important clues to the diagnosis. A family history of certain types of headaches may also shed light on the etiology. For patients with more than one type of headache, a separate history should be obtained for each type.

Table 77-4 Eliciting History: Questions to Ask Patients about Headaches

Physical examination of a patient with headache must include a full neurological examination, a funduscopic examination, and an examination of the head. Vital signs must also be assessed (as low or high blood pressure may be contributing factors). A fever may point toward a central nervous system (CNS) infection. The neurological examination will reveal any focal findings that may indicate a stroke or multiple sclerosis (MS). The funduscopic examination will search for signs of raised intracranial pressure (ICP), manifest by papilledema (Figure 77-2).¹⁴ Physical examination of the head will search for signs of trauma, and one should palpate for tenderness or masses, and listen over the temples and eyes for bruits that may signal the presence of an arterial-venous malformation. The neck must also be checked for rigidity.

Figure 77-2 Papilledema. Asymmetric papilledema in a 54-year-old woman with constant daily headaches and transient visual loss in the right eye. She had idiopathic intracranial hypertension.

(From Friedman DI: Headache. In Schapira AHV, Byrne E, editors: Neurology and clinical neuroscience, Philadelphia, 2007, Mosby, Fig 61-1, p 809.)

Further testing may be indicated to evaluate etiologies suggested by the history and physical examination (Table 77-5). Imaging may be needed if a brain mass, stroke, or MS is suspected. Computed tomography (CT) scans are usually quicker and cheaper whereas magnetic resonance imaging (MRI) is more sensitive and expensive. A lumbar puncture (LP) can help evaluate infectious etiologies, subarachnoid hemorrhage (SAH), or ICP. In an elderly person with new-onset headache, an elevated erythrocyte sedimentation rate (ESR) suggests giant cell arteritis or temporal arteritis. Electroencephalography (EEG) and evoked responses have no particular role in primary headache diagnosis but may be helpful in sorting out several of the secondary headache causes.

Table 77-5 Ordering Laboratory and Other Tests

CNS, Central nervous system; CRP, c-reactive protein; CT, computed tomography; CVT, cerebral venous thrombosis; EEG, electroencephalogram; ESR, erythrocyte sedimentation rate; LP, lumbar puncture; MRA, magnetic resonance angiogram; MRI, magnetic resonance imaging; MS, multiple sclerosis.

HEADACHE “RED FLAGS”

Historical features that may indicate a dangerous underlying cause for headache include the so-called “first and worst” headache, that is, the sudden onset of a de novo severe headache, possibly indicating an SAH often as a result of an aneurysmal bleed. Also known as a “thunderclap headache,” this pattern has been investigated in some detail, and there is a differential diagnosis beyond SAH, with both primary and secondary types described (Table 77-6). Some of these headaches are actually of benign origin with a negative evaluation; however, given the risks involved in missing an aneurysmal bleed, this pattern cannot be assumed to be benign and must be evaluated.

Table 77-6 “Thunderclap” Headache

Headache associated with fever, chills, and change in mental status is of evident concern and not often confused with a primary headache syndrome. Similarly, a new-onset headache in a compromised individual (e.g., someone with acquired immunodeficiency syndrome [AIDS]) or in someone with a concerning past medical history (e.g., with metastatic cancer) should also prompt concern.

New-onset migraine after age 50 is unusual, and thus an evaluation (including an evaluation for temporal arteritis) is warranted, to prevent the often sudden complication of irreversible visual loss.

OTHER SECONDARY HEADACHES

Not all secondary causes of headache pose an immediate danger. Nonetheless, accurate diagnosis of such secondary causes (e.g., low pressure headache or cervicogenic headache) should result in more targeted and productive therapy; thus, vigilance in rooting out secondary causes of headache is warranted. And, since known migraine patients may themselves develop secondary headaches, combinations of types of headache may be present in one individual causing significant diagnostic confusion.