Almost everyone experiences a headache at some point in their life. In fact, approximately three-fourths of all adults in the United States experience some type of headache each year. The prevalence of headache varies by gender, with women having a greater incidence of headaches than men. It has been estimated that nearly nine out of ten women, and seven out of ten men, have a headache at least once during her/his lifetime [4]. In developed countries, tension-type headache is more common in women, usually by a factor of about two to one [3].

In most cases, headaches are transient and benign. People simply treat the headache with either rest and/or relaxation, or they utilize various over-the-counter analgesics. In fact, the public spends more than $2 billion annually on over-the-counter medications to treat headaches [5]. Less than 5% of adults with headaches seek medical attention. Even with this small percentage, however, headaches are one of the most common complaints addressed by primary care physicians and clinicians and represent the reason for nearly 3% of all visits to the emergency department [1].

People typically seek medical care when they have increased headache frequency, an unusually intense headache, or persistent symptoms. Headaches can be one of the most difficult and challenging disorders to accurately diagnose and treat, so it is important for physicians and other clinicians to become familiar with the latest evidence on headache diagnosis and management.

Headaches are a costly condition. It has been estimated that headaches are responsible for nearly 30 million days of lost productivity, both in terms of lost days at work, as well as decreased effectiveness while at work. Headaches cost an estimated $18 billion in both direct and indirect expenditures yearly. Most costs are indirect as many headache sufferers do not seek medical attention [2,7,8,9].

Secondary headaches, as the name indicates, occur secondary to another cause (i.e., they are a symptom of other diseases). These may include vascular, traumatic, neoplastic, infectious, pressure, and metabolic disorders [11]. Secondary headaches account for only 10% of headaches. Although some causes of secondary headache are common, others are important to recognize because they are dangerous and may require specific treatment [12]. For example, patients with chronic tension headaches may present with an epidural hematoma, and patients with migraine may have a brain tumor. Primary and secondary headaches should not be considered mutually exclusive when evaluating a patient with headache. It is helpful to consider secondary headaches in terms of etiologic categories. Some of the more common causes of secondary headaches are as follows [13]:

Although most headaches are benign, clinicians should be aware of the following "red flags" or warning signs that should prompt an immediate and exhaustive work-up and possible referral to an appropriate specialist for further assessment [5,13,20,21,23]:

Electroencephalogram (EEG) is not frequently used and not recommended in the routine work-up of headaches. It has minimal value in determining any structural causes of headaches. It may be useful, however, when patients present with encephalopathy, focal neurologic deficits, atypical aura symptoms, or altered consciousness [21,22,24].

CT scans may be performed either with or without contrast. Unless there is a contraindication to the use of contrast agents, most scans are performed with contrast in the diagnostic work-up of headaches. A contrast-enhancing CT scan can be an effective test for identifying several serious lesions that may be causing headaches [33,34].

CT is usually obtained in the setting of trauma or the abrupt onset of headache [27]. Primary indications include acute head trauma, suspected acute intracranial hemorrhage, mental status changes, headache, acute neurologic deficits, suspected intracranial infection or hydrocephalus, brain herniation, and suspected mass tumor. It may also be used in cases in which MRI is primarily indicated but unavailable, contraindicated, or delayed [34].

In general, CT scans are widely available, quickly performed, and well-tolerated by patients. The technology has been around for quite some time, and most patients are familiar with it [34]. In addition, there are "open" CT scanners that help minimize the feeling of claustrophobia some patients experience. This scan detects most space-occupying lesions such as brain tumors, subdural hematomas, and CNS abscesses. It can also show fluid from hydrocephalus and cerebral edema, and it can reveal bleeding and structural abnormalities such as some arteriovenous malformations. However, CT scanning can miss aneurysms, and it also does not provide adequate views of the sphenoid sinus. Adding "bone windows" on CT provides much better detection of skull fractures, especially as compared to plain films.

The U.S. Headache Consortium has issued guidelines relating to neuroimaging in patients with nonacute headache. The guidelines include three consensus-based general principles of management [22]:

Approximately 3% to 5% of patients with migraine experience an aura without headache. This presentation, formerly known as a "migraine equivalent," tends to occur in older individuals who have had a history of migraines with aura in their earlier years [45]. They predominantly occur in men of advanced age.

Many different factors work to trigger migraines. These factors vary greatly from one individual to another and often no precipitating events can be clearly identified. Trigger factors increase the probability of a migraine attack in the short term (i.e., usually in less than 48 hours) in a person with migraine. Some of the more common triggers include stress, sleep disturbances, depression, low barometric pressure, food, hormonal variations, and caffeine withdrawal. Some trigger factors have been reasonably well studied epidemiologically (e.g., menstruation) or in clinical trials (e.g., chocolate, aspartame); however, causal attribution in individual patients may be difficult[43].

Acute attack pharmacologic options are used at the onset of the attack. They can be divided into nonspecific and specific drugs. The nonspecific therapies are single or combination analgesics. Routes of administration include oral, nasal, parenteral, and rectal. Appropriate situations for use, including potential side/adverse effects, drug-drug interactions, and patient-specific contraindications, should be addressed. Opioids are generally avoided, if possible, due to concerns about tolerance and dependence [54,173].

The more common analgesics used include acetaminophen, NSAIDs (e.g., aspirin, ibuprofen, naproxen sodium), and narcotics (e.g., oxycodone, morphine sulfate) [38]. Acetaminophen-aspirin-caffeine combination may also be used to treat migraines. The evidence for efficacy is most consistent for aspirin, ibuprofen, naproxen sodium, and the acetaminophen-aspirin-caffeine combination. Acetaminophen alone has been found to be ineffective [53,66,173].

In the 2000 AAN guidelines, the NSAID diclofenac was considered "probably effective" for the acute treatment of migraine. Class I studies conducted since that time resulted in the agent being reassessed by the AHS as "effective" (Level A) [14,176,177].

The nonspecific therapeutic drugs may be used to relieve the pain through many different mechanisms, although most typically work by dulling pain receptors. These are usually considered first-line therapeutic options for many individuals who find these adequate in obliterating headaches [54]. In order to increase the likelihood of efficacy it is important that these are taken as early as possible in the headache cycle [38]. In addition, a large single dose tends to be more effective than repeated smaller doses. When any of these medications are used, many clinicians add an antiemetic or pro-motility agent to increase the chance of absorption, especially during an attack when nausea is a major component [53].

Over-the-counter analgesics are often effective in treating migraine. In an observational study of the impact of over-the-counter analgesics for migraines on a patient's quality of life, nearly 100 patients who used over-the-counter medications, such as acetaminophen-aspirin-caffeine combination, and who also received educational migraine materials over a four-month period completed a general health status questionnaire. At the end of the study, patients reported significant improvements in several quality-of-life measures and increased frequency of relief [69].

Cluster headache is among a group of five disorders called trigeminal autonomic cephalalgias, characterized by unilateral pain in the region of the trigeminal nerve. Cluster headache is defined as a primary type headache consisting of short (15 to 180 minutes), frequent (up to eight times per day), unilateral attacks of headache and facial pain with associated ipsilateral autonomic features and generalized restlessness [43,53,191]. Patients often experience delayed diagnosis and suboptimal treatment as cluster headache tend to be confused with migraine and trigeminal neuralgia. The term "cluster" refers to the recurring pattern of symptoms experienced by 80% of patients: symptomatic periods each year, typically in the same season, when the patient suffers headache attacks daily for one to three months at a time, then is symptom-free the remainder of the year [191].

When the disorder is active, the periodicity of cluster headache attacks may vary from every other day to eight times per day. Attacks are accompanied by one or more of the following symptoms: ipsilateral conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhea, ptosis and/or miosis, eyelid edema, forehead/facial sweating, forehead/facial flushing, or sensation of fullness in the ear (Table 10). Attacks occur in series lasting for weeks or months separated by remissions lasting for months to years[43].

Tension headaches are among the most common headache type seen in practice today; however, it is the least studied of the primary headache disorders despite having the highest socioeconomic impact. The lifetime prevalence ranges from 30% to 78%, with a rate of 63% seen in men and 86% in women [21,43].

The etiology of tension headaches is multifactorial. Although once thought to be simply secondary to muscle spasm, it is now felt that other factors play important roles. In fact, although tension headaches may arise from sustained contraction of pericranial muscles, no correlation exists between muscle contraction and the presence of a tension headache. It seems that, just as in migraine headaches, tension headaches arise in part from centrally mediated neural dysfunction. This abnormality may in part be due to central sensitization in the trigeminal area[43,67].

Tension headaches also tend to respond well to medications. Some commonly used medications that are effective include aspirin, acetaminophen, and NSAIDs in the standard prescribed doses [114]. Combination treatments with the above medications and caffeine, butalbital, and muscle relaxants are also effective. However, overuse of these medications, especially those containing caffeine, may lead to rebound headaches. The use of butalbital also may result in dependency, and for this reason, it is not recommended for prolonged use [53,73]. In general, narcotics should be avoided because tension headaches are typically mild-to-moderate in pain intensity. Botulinum has also been suggested for the treatment of tension headaches; however, not all researchers agree that it should be used for chronic tension-type headache [11,116]. As discussed, however, more study regarding efficacy and safety is required.

As noted, it is helpful to think of secondary headaches in terms of etiologic categories, such as vascular, traumatic, neoplastic, infectious, pressure, metabolic/toxic ingestions, and medication overuse. A secondary headache may be diagnosed when another disorder known to cause headache has been demonstrated; headache occurs in close temporal relation to the other disorder and/or there is other evidence of a causal relationship; and headache is greatly reduced or resolves within three months (this may be shorter for some disorders) after successful treatment or spontaneous remission of the causative disorder. The IHS has divided secondary headaches into subtypes attributed to specific causes[43].Table 15shows a summary of several causes of secondary headache.

Hemorrhages usually occur in the temporal fossa from middle meningeal artery tears; they may also occur in the posterior fossa as a result of a transverse sinus tear. Posterior fossa epidural hematoma may exhibit a rapid and delayed progression from minimal symptoms to even death within minutes. Overall mortality has been estimated to be as high as 50%, so prompt evaluation and treatment is critical [43].

With respect to diagnosis through neuroimaging, in the acute setting, unenhanced CT scan is more useful than MRI imaging. Epidural hematomas have a characteristic white lenticular shape adjacent to the bone, while focal hypodense or isodense areas on CT indicate active bleeding. Because the temporal fossa is often involved, one must be careful that bony artifacts do not obscure a hemorrhage [121].

As the name implies, subdural hematomas occur between the surface of the brain and the dura. The source of bleeding is the venous system (i.e., bridging veins) as opposed to the arterial system. Because the subdural space is continuous, these types of hemorrhage may have significant mass effect. Subdural hematomas are more common than epidural hematomas. They tend to evolve more slowly based on the slower rate of venous bleeding compared to arterial hemorrhage. As a result, there may be a progression of symptoms over two to four weeks; the rate of progression depends upon the severity of the injury [122].

Patients often present with a mild persistent headache. There may be drowsiness and confusion, although focal neurologic signs are often absent. Symptoms may be followed by a brief lucid interval with subsequent deterioration. Subdural hematomas are seen in approximately 15% of all head traumas. Automobile accidents are a typical cause of subdural hematomas [122].

Prompt treatment is critical because mortality can reach 60%. Treatment may include diuretics to reduce swelling. Because there is a high frequency of seizures, antiepileptics are frequently used to either control or prevent seizures. For more serious hematomas, surgical evacuation may be necessary. The long-term prognosis is actually worse than that for epidural hematomas [122,123,124].

Typically, headache due to an SAH is described as a sharp pain that usually involves the entire head. Patients classically describe it as the "worst headache of their life." It often radiates into the neck and even into the back. There is usually nausea and vomiting. In general, there are no focal neurologic deficits early on, but as it progresses, there may be loss of consciousness and altered mental state. Seizures during the acute phase occur in 10% to 25% of patients [125].

The prevalence of SAH increases with age in a linear relationship. The mean age is 50 years [125,126,127]. On physical examination, the patient is typically in severe pain. The pain is sometimes referred to as a "thunderclap" headache [126]. Symptoms of meningeal irritation, such as nuchal rigidity and pain, back pain, and bilateral leg pain, occur in as many as 80% of patients with SAH but may take several hours to manifest [126]. Focal neurologic deficits, such as facial droop or weakness in a specific extremity, are present in 25% of patients. However, if the hemorrhage is associated with ischemic stroke it will likely involve the brain parenchyma, which may lead to hemiparesis, aphasia, or visual field abnormalities. Loss of consciousness is transient [43,125].

On exam, the affected scalp artery is sometimes prominent. It may be tender and is often pulseless. The scalp itself is usually tender as well. Depending upon the progression, visual field defects and decreased acuity may be noted, although the patient does not usually exhibit focal neurologic deficits. Typically, the headache occurs in someone who is febrile, has malaise, and feels aches in the back and shoulders. Jaw claudication (pain on chewing food) occurs commonly and is virtually pathognomonic for this condition when present during talking or chewing [129].

Headache, migraine, and stroke are common and can be temporally related, but a direct causal association has not been definitively proven in clinical studies. Headache may be coincidental with stroke (also referred to as cerebrovascular accident or stroke syndrome), including both ischemic and hemorrhagic stroke, or it may be a consequence of stroke. Headache or migraine may increase the risk of stroke [131]. Results of the Women's Health Study, presented at the 2013 International Headache Congress, reported that migraine with aura is a strong risk factor for any type of stroke [132,133,134]. Headaches associated with stroke are typically reported as dull but diffuse (35%) [135]. They are not localized to a particular side. In addition, headache presentation of a stroke is more common in patients younger than 40 years of age [135]. Headache is more likely to occur in combination with other signs and symptoms of stroke [132]. Depending upon the type of stroke, there may be a focal neurologic deficit, such as aphasia or dysarthria. Young patients should be evaluated carefully to avoid misclassification of stroke as a complicated migraine [135].

CSF examination is critical to establish the diagnosis and reveals moderate monocytosis and erythrocytosis with a variably elevated protein level. EEG is sensitive but not specific, and contrast CT is only 60% sensitive. It may be used, however, to evaluate acute disease progression and to follow up on complications. MRI is more sensitive than CT scan [142]. MRI with gadolinium enhancement is the preferred imaging study. One should keep in mind certain seasonal and geographic issues when differentiating specific etiologic agents.

The cardinal clinical features of acute rhinosinusitis are nasal congestion/obstruction, purulent nasal discharge, and pain (regional facial pain and/or headache), Patients may exhibit low-grade fever, though this is more common in children [43]. Regional pain is often described as a deep, dull, heavy sensation of pressure or fullness that sometimes may be throbbing. Bending forward, shaking or flexion of the head, coughing, and sneezing exacerbate the pain. Sinus headache is seldom associated with nausea and, except for sphenoiditis, does not reach the same pain intensity of cluster headache or migraine. The diagnosis of sinusitis is most often made by careful clinical assessment, including sinus transillumination for suspected frontal or maxillary disease. In select cases, plain radiographs of the face ("sinus views") are helpful, as they may show clouding or air-fluid levels in the involved sinus [144]. Diagnosis may be facilitated by Gram stain and culture of purulent discharge directly from the sinuses; however, this technique is not commonly performed in the primary care office setting. Neuroimaging is usually reserved for evaluation of persistent, recurrent, or complicated cases. A CT scan is highly sensitive and is the neuroimaging modality of choice in evaluating sinusitis, particularly cases of chronic sinus disease [144]. MRI is generally preferred for the evaluation of sphenoid sinus disease, and for suspected intracranial extension of infection (e.g., orbital cellulitis, abscess).

The time course of an abscess is reflected in the symptoms and usually progresses over one to two weeks [147]. Diagnosis is aided by CT, MRI, and nuclear medicine studies. In general, MRI provides better brain parenchymal differentiation than CT and shows the edema from the abscess in better detail [147]. The abscess is also better demonstrated because the routine brain MRI generally is multiplanar, as opposed to the routine CT, which is usually axial. However, MRI may not be useful in an acutely ill patient [146]. MR spectroscopy and some nuclear medicine studies may also be helpful to differentiate abscess from brain tumor [146]. Diffusion weighted MR may also give early indication of an infarction because this may be part of the sequelae of the abscess. Lumbar puncture is contraindicated due to its poor diagnostic yield and possible risk of herniation of the cerebellar tonsils [146,147].

Syringomyelia is an uncommon presentation of headache. It is a condition in which a cyst forms within the spinal cord, either congenitally or due to trauma, malignancy, infection, or hemorrhage. In most cases, the disorder is related to a congenital abnormality of the brain called a Chiari malformation. This malformation occurs during the development of the fetus and causes the lower part of the cerebellum to protrude from its normal location in the back of the cranium into the cervical portion of the spinal canal [160].

The cyst, or syrinx, gradually expands and elongates over time, eventually resulting in destruction of the cord's center. As a result, patients may present with a variety of symptoms, although they typically present with headache, back pain and stiffness, and numbness of the extremities [160]. Symptoms usually begin between 25 and 40 years of age; they are more common in men than women and may worsen with straining (e.g., heavy lifting) or any activity that causes CSF pressure to fluctuate [160].

Medication overuse headache, also known as rebound headache, results from misuse of drugs, most notably over-the-counter analgesics or migraine medications. It is most common in patients with frequent migraine attacks or tension-type headaches [165]. Chronic tension-type headache is less often associated with medication overuse; however, episodic tension-type headache has commonly become a chronic headache through overuse of analgesics [43]. The headache is caused by frequent use of anti-headache medications for more than 15 days per month. Evidence suggests that this occurs sooner with triptan overuse than with ergotamine overuse [43,166]. The mean period of time that elapses before this type of headache evolves ranges from one to two years for the triptans, three to five years for ergotamines, and up to 5 to 10 years for over-the-counter analgesics [167]. The pathophysiology of this syndrome remains unknown.

The diagnosis of medication-overuse headache is clinically extremely important because patients rarely respond to preventative medications while overusing acute medications [43]. Treatment is withdrawal from the medication. If tapered, this may take more than two weeks, depending on the medication. Improvement should occur within two months after cessation of overuse in order for the diagnosis to be definite [43]. This is followed by prophylactic treatment of the primary headache [165,166].

Although chronic headache is a term often used by patients, as well as some clinicians, it is no longer a recognized diagnosis. Patients either have a chronic primary headache or a chronic secondary headache. Chronic daily headache occurs in approximately 4% to 5% of the population [170,171]. The overwhelming majority of chronic headaches are primary headaches, typically migraine or tension. Chronic headache is not a separate syndrome. The general time frame for chronic is when the headache occurs on more than 15 days of each month, whether or not the patient is taking any medication.

One of the most important decisions in managing patients with headaches, especially chronic headaches, is when to continue care and when to refer care. In general, most patients with benign headaches can be managed by primary care physicians and other clinicians. There are several factors involved when one should consider referral to a specialist. These include, but are not limited to:

With rising malpractice premiums, the threat of malpractice remains high on the minds of many healthcare professionals. With respect to headaches, physicians are fearful of missing that rare brain tumor or other catastrophic cause of headache. When such a misdiagnosis occurs, a malpractice claim may ensue. Any malpractice action falls under tort law.

Tort law allows injured persons to recover damages through the civil (i.e., noncriminal) judicial system. It is important to note that injury is a necessary but not sufficient requirement for recovery and most injuries do not give rise to a legal action. In the context of medical malpractice suits, the most relevant aspect of tort law is negligence as that is the claim most plaintiffs raise. A common claim for headache management is "failure to diagnose."