Headache:
an outpatient approach to diagnosis and management
Dolores J. Bacon, M.D.
Headache,
one of the most common complaints of patients seen in the primary care setting,
accounts for over 10 million outpatient visits per year in the United States,
and about 20% of all referrals to neurologic specialists.1 Although patients are often quite concerned that their
headaches represent serious underlying illness, most headache syndromes have a
benign prognosis. For example,
although most patients who believe their headaches are due to an ominous cause
suspect that they have a brain tumor, the overall incidence of headache of a
central nervous system neoplasm is less than 9 per 100,000.2
Diagnosis
and management of headache in the outpatient setting can be challenging for
various reasons. One is that the
list of various headache types is extensive; in 1988 the International Headache
Society prepared a list of specific diagnostic criteria for 129 different
headache syndromes.3 In
addition, an increasing number of patients present with many chronic problems or
complaints, and often minimize their headache or mention it only as the visit
draws to a close. Attempting to
make an accurate diagnosis in a limited amount of time is often a source of
consternation, for one does not wish to overlook a potentially life-threatening
cause of the headache, yet a cost-effective approach to evaluating what usually
represents a benign disorder precludes the routine use of laboratory tests and
neuroimaging modalities. The most
practical approach begins with an accurate, focused history.
This is the most important element of evaluating the patient with
headache, and allows the clinician to quickly decide if the symptoms suggest a
primary headache disorder (which is benign), or a secondary headache disorder
(which, if underdiagnosed and untreated, results in serious morbidity and/or
mortality). Having categorized the
headache, time management decisions are made more simply and appropriately, and
the evaluation proceeds accordingly.
Particular attention should be paid to the following details of the history:
·
Onset
Always
ask when the headache first began. A
longstanding, episodic headache pattern suggests a benign course, while a
headache of recent origin, acute onset, or with progressive features usually
requires an investigation with CT scan or magnetic resonance imaging and may
lead to diagnostic procedures such as lumbar puncture, temporal artery biopsy,
etc. The age at onset can also
provide clues. Secondary causes of
headache such as tumor, temporal arteritis, or leaking aneurysm are more
prevalent in those over the age of 35; benign syndromes (migraine, tension-type
headache, cluster headache) most often occur for the first time before the age
of 35.
·
Duration and timing
This can help narrow the diagnosis in most cases. Migraine headaches can last from hours to a few days; tension headaches are often present daily for weeks at a time, while cluster headache is episodic, occurring at the same time daily for 4 to 16 weeks.
·
Location and quality
It is often difficult for patients to describe the pain, which can be throbbing, lancinating, tight, pulling, burning, etc. A unilateral, throbbing pain is common in migraines; tension-type headaches are often described as a tight, band-like sensation circling the head; headaches localized only to the occipital region can be due to tumor, and the pain of a cluster headache is excruciating and usually located behind one eye.
·
Severity
This is a very subjective symptom, but is important when assessing the patient’s complaint. To get the most clinically useful information, ask the patient how the headache affects his daily activities, rather than how severe the pain is. A headache that interferes with normal daily activity and requires bed rest is considered to be severe.
·
Aggravating/relieving factors
This line of questioning can greatly help in narrowing the diagnosis. Often patients with cluster headaches will say that nothing helps, and they typically are not able to sit still. Many patients with migraine report that lying down in dark, quiet surroundings is helpful. They may also report that the pain is made worse by ordinary physical activity, such as climbing stairs. A headache that is worse in the morning upon arising or that is significantly exacerbated by straining, lifting (i.e. Valsalva maneuver) suggests a tumor or other intracranial lesion.
·
Associated symptoms
Many foods, including those containing tyramine (red wine, liver, aged cheese, nuts), and those containing monosodium glutamate (canned vegetables, delicatessen or processed meats, Chinese food), as well as alcohol, caffeine and nicotine can exacerbate or trigger migraine. There is an increased frequency of smoking among patients who have cluster headaches. Valuable information is gained from obtaining the patient’s past medical history and current medications. This may uncover the use of medications known to be associated with headaches (for example, calcium channel antagonists), or frequent use of analgesics, combination preparations or narcotics, which suggests a rebound or withdrawal headache. Ask specifically about over the counter medications as patients often forget to mention these.
·
Family history, menstrual
history, psychosocial history
In migraine, there is a strong familial association, so a family history of recurring headaches provides a clue. In female migraineurs, the headaches often occur or are worse during menses. Depression or anxiety should be addressed, and may be related to tension-type headaches. Lack of sleep, too much sleep and stress can be associated with tension-type headaches and are also migraine triggers.
The secondary headache disorders are those caused by a serious underlying pathologic (structural or metabolic) process, and should be immediately screened for with the appropriate headache history, physical exam, and in some cases laboratory evaluation (see below). The most common causes of secondary headache are:
·
Subarachnoid hemorrhage
·
Mass lesion
·
Temporal arteritis
Other causes include subdural or intracranial hematoma, cerebral ischemia (stroke or TIA); acute meningitis; hypertension; acute angle closure glaucoma; Lyme disease; internal carotid artery dissection; cerebral vein thrombosis; pseudotumor cerebri.
Primary
headache disorders are the most common, and are headaches with no underlying
metabolic or structural cause. They
include:
·
Tension-type headache
·
Cluster headache
·
Migraine headache
·
Post-traumatic headache
·
Drug withdrawal or rebound headache
The Physical Exam
Although the physical exam is needed to help confirm the diagnosis and rule out secondary headache causes, a complete neurological exam is not necessary nor does it yield more diagnostic information than a focused exam. The entire exam may be performed quickly, and should include the following:
·
General
appearance:
Does the patient appear acutely ill?
Are there gross abnormalities of gait?
·
Vital
signs:
Check the temperature and blood pressure
·
Mental
status:
Does the patient have normal speech; is he alert; can the patient give a
reasonable history (formal testing of memory is not necessary)?
·
Head
and neck exam:
Check scalp for areas of tenderness or swelling; examine fundi; palpate
temporal artery; assess flexibility of cervical spine and feel for spasm or
tenderness in the muscles of the neck and shoulders; look for facial asymmetry;
observe extraocular eye movements and pupillary reaction to light; check the
temporomandibular joints for range of motion and presence of clicking or
crepitus
·
Neurological
exam:
Pinprick sensation should be perceived equally on both sides of the face,
in arms and legs; check visual fields by confrontation; evaluate motor system by
observing tandem gait; having patient open and close fist in repetitive fashion,
checking Babinski and deep tendon reflexes (patellar).
The cerebellar exam should be included as well (finger to nose) and
muscle strength should be quickly assessed in the upper and lower extremities.
In most cases, laboratory tests are not indicated. When the history suggests a serious etiology of the headache complaint (see Table 1), there are some tests that are helpful (for example, a complete blood count with differential in a patient with fever/systemic symptoms). A good rule of thumb is to check an erythrocyte sedimentation rate (ESR) in a patient with a new onset or change in a stable headache pattern after the age of 50. It must be emphasized that often patients do not immediately recall all of the aspects of their headache pattern, give conflicting history, or simply have so many other complaints in the same visit that there is not sufficient time to clarify certain elements of the history. Often the single best “test” the clinician can perform is to schedule a follow up visit to re-evaluate the symptoms and history.
Neuroimaging
Although this is usually not necessary, there are specific cases in which an MRI or CT scan should be done, such as in a patient who presents with:
·
Headache
that is progressively worsening or that is clearly different than the usual
headache syndrome
·
Onset of
headache occurring after 50 years of age
·
A headache
associated with an abnormality on neurological exam
·
The acute
onset of an extremely severe “worst ever” headache
· Headache associated with sexual activity, exertion, coughing or sneezing (suggestive of posterior fossa disease)
A CT scan
should be used if acute hemorrhage is suspected, as it is superior to MRI in
this respect, or to check for tumor, hydrocephalus or cerebral atrophy.
If posterior fossa disease is suspected, an MRI rather than CT scan is
indicated. MRI with MR angiography
is used for visualization of vascular lesions such as aneurysms.
Lumbar puncture (LP)
Evaluation
of the cerebrospinal fluid is mandatory if a subarachnoid hemorrhage is
suggested by clinical findings but the CT scan is negative.
It is indicated as well if the history and/or physical exam suggests an
infection such as meningitis. The
lumbar puncture is contraindicated if a space-occupying lesion is suspected, so always
check fundi, reflexes and Babinski.
Electroencephalogram (EEG)
There are no indications for this procedure as a diagnostic tool for headache.
As mentioned earlier, the primary headache disorders are benign in nature and therefore do not require emergent intervention. Nonetheless, appropriate diagnosis and management of these headache syndromes is important, given the significant impact of untreated or misdiagnosed headache on the patient’s quality of life and daily level of functioning, as well as the cost of days missed from work and increased number of visits to doctor’s offices or emergency rooms. The primary headache disorders include migraines, tension-type headaches, cluster headaches, drug rebound headaches, chronic paroxysmal hemicrania, and hypnic headache.
Tension-type
headache
Tension-type headache accounts for the majority of headaches experienced in the general population as well as the geriatric population. This term includes the headache syndromes that were previously referred to as tension headache, psychogenic headache, and muscle contraction headache. Tension-type headache is classified as episodic or chronic,3 and occurs mostly in women – three-quarters of those with tension-type headache are women. The reason for this remains unclear. Episodic tension-type headache is not often seen in the office setting because it is self-limiting and usually responds to rest, relaxation, or over-the-counter medications. Chronic tension-type headache involves recurring discomfort for at least 6 months, and occurs almost daily. According to the International Headache Society diagnostic criteria for tension-type headache, the headache must be present for more than 15 days per month and for longer than 6 months.
Clinical characteristics
In most cases, the pain is bilateral and is frequently described as tightness or pressure located in a band-like distribution around the head. The pain is moderately intense and lasts for hours, but unlike some migraine headaches, is not severe enough to be disabling and is not exacerbated by physical activity nor associated with nausea, vomiting, phonophobia or photophobia. There are usually no findings on physical exam, but some patients may have scalp muscle contraction, cervical muscle or trapeziums muscle tightness and tenderness. The patient may have an anxious or depressed affect but the neurological exam is otherwise non-focal.
Pathogenesis
It has long been felt that muscle spasm in the scalp and neck muscles is directly related to the etiology of tension-type headaches, but the actual physiology remains unknown, and there is controversy as to whether the muscle contraction represents a primary process, or is merely secondary to an underlying central dysfunction. Although muscle contraction in some patients has been demonstrated by certain EMG studies in which increased action potentials correlated with pain in the scalp and neck muscles, data are conflicting. The methods of study are variable, as are the protocols, and some studies did not show any correlation at all between pain severity and degree of muscle contraction.
Etiology
The most common cause of tension-type headache is stress or anxiety. It is not unusual for the headache to develop in anticipation of, during, or after an identifiable stress or unpleasant event. In patients with chronic, not episodic tension-type headache, the most important etiologic factors are depression and drug habituation. This most often results from the daily use of caffeine, over-the-counter-medications, prescribed analgesics, barbiturates or narcotics in an attempt to alleviate the chronic discomfort.
Occupational causes of tension-type headaches must be considered as well. Common examples are neck and shoulder spasm resulting from prolonged work in a constant position (work at a computer terminal or factory/assembly line work), and long hours seated at a desk with poor posture. Development of a tension-type headache after reading, watching television or doing computer work can occur in patients with eye conditions such as astigmatism and convergence insufficiency.
Other etiologies include underlying causes of cervical muscle spasm, such as cervical spine disease, muscle spasm resulting from neck injury or trauma, or conditions that result in orofacial pain such as temporomandibular joint disease. Degenerative disc disease of the cervical spine is quite prevalent, and although many patients with radiologic evidence of degenerative changes in the facet joints of the upper cervical spine are without headache complaints, degenerative disease or spondylosis can cause cervical muscle spasm leading to cervical myalgia, scalp muscle contraction, and headache.
Evaluation
A careful history and thorough, focused, physical exam is mandatory. Laboratory investigations are rarely necessary and should be done only when indicated by history and physical findings, such as radiographic studies of the cervical spine to demonstrate degenerative disc disease if present. All medications taken by the patient must be reviewed carefully, as many patients do not consider over-the-counter preparations to be medications and may not volunteer that they are taking any. Caffeine intake should be evaluated. It a common ingredient in many combination analgesics (over-the-counter and prescribed), and if taken regularly, can cause rebound headache. As with all headache syndromes, the first goal of the history and physical is to classify the headache as primary (benign) or secondary, thereby identifying those patients who require immediate medical intervention.
Management
The acute tension-type headache is easily managed with simple analgesics such as acetaminophen or non-steroidal anti-inflammatory agents such as ibuprofen. These headaches are usually self-treated, with the patient often identifying areas of stress in his daily life and may take steps to eliminate them. The patient generally self-medicates with over-the-counter preparations, and rarely seeks medical attention.
Chronic tension-type headaches are far more difficult to manage, as these patients are frequently dependent on the medications that have been prescribed, resulting in rebound headache. In severe cases of analgesic dependence, the patient must be hospitalized because of the withdrawal symptoms associated with cessation of the medication. Many physicians are aware of this potential complication when prescribing narcotics but fail to realize the significant risk of habituation and dependence associated with the use of combination agents containing mild sedatives, such as the acetaminophen/caffeine/butalbital combination known as Fioricet. For this reason, a key question to be asked of all patients with a chronic headache syndrome is the number of headaches experienced per week. In a patient who has more that two headaches per week, the use of narcotics, tranquilizers, sedatives or combination analgesics containing butalbital or dichloralphenazone should be avoided.
Long acting non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen are often very helpful, especially if used in conjunction with other agents or treatment modalities, depending on the underlying etiology of the tension-type headache. Of course, caution is to be taken with the chronic use of these medications, especially in the elderly, because of the side effects associated with long term use, the most prominent being gastrointestinal bleeding and ulcer formation. Renal dysfunction (acute interstitial nephritis, increased serum potassium, acute renal failure) has been associated with high-dose or long-term NSAID use.
Antidepressant medications have been used successfully in the treatment of chronic tension-type headache, and in the depressed patient with this type of headache, psychological counseling is often an important adjunct to antidepressant therapy. The most widely used antidepressant agent used for chronic tension-type headache is amitryptyline. Tricyclic antidepressants are contraindicated in patients with hypertension, closed-angle glaucoma, urinary retention, arrhythmias or intestinal obstruction. Be aware of the anticholinergic effects associated with this class of medications, which include syncope, orthostatic hypotension and cardiac dysrhythmia. This is of special concern in the elderly, who are more sensitive to anti-cholinergic effects. An alternative that may be used in the presence of significant anti-cholinergic side effects is
trazodone, a non-tricyclic antidepressant that is somewhat sedating. Care should be taken in selecting this agent as there is a slightly increase risk of ventricular arrhythmia (a baseline EKG should be obtained and the QT intervals monitored periodically).
Although the monoamine oxidase inhibitors (MAOI) are also effective, they are not a frequent choice due to their side effect profile and limitations associated with prescribing them. The selective serotonin reuptake inbibitors (SSRI) are associated with far fewer side effects, but unfortunately are not very affective as treatment in those patients with chronic tension-type headache in which depression is not the underlying cause.
Muscle relaxants may be helpful when used in combination with NSAIDS and local application of heat or ice in patients whose symptoms are associated with significant muscle spasm. As a group, they are sedating, have the potential for dependency, and in the elderly population must be prescribed with extreme caution and only if clearly indicated. Cyclobenzaprine, taken at bedtime only, can be used with good results but diazepam should never be used as treatment of any chronic headache because of the high risk of dependency.
Non-pharmacologic treatment is extremely helpful and includes physical therapy and biofeedback. Any techniques that induce relaxation are beneficial and should be encouraged. Acupuncture has been shown to be successful in some patients, but the outcome cannot be predicted with consistency.
Migraine
headache
Migraine is a chronic, benign, episodic disorder characterized by recurrent headaches that are often severe and usually associated with nausea and sometimes vomiting. The headache is often preceded or accompanied by sensitivity to light (photophobia) or sound (phonophobia) and transient cognitive and/or visual impairment. It is relatively common, affecting 10-20% of the population (about 23 million individuals), but unfortunately remains underdiagnosed. This has a tremendous social and economic impact, with the cost of lost productivity estimated to be between 6.5 – 17.5 billion dollars yearly.4
The concept that fluctuating estrogen levels play a key role in the pathophysiology of migraine is supported by prevalence data. Migraines are most prevalent in women (18%) with a male-to-female ratio of approximately 1:3, and peak incidence occurring between the age of 25-34. Prior to the onset of puberty, the incidence of migraine is the same in females, and the headaches decrease markedly or disappear after the onset of menopause. 70-80% of female migraineurs report an association between migraine symptoms and the menstrual cycle, and 14% of them have true menstrual migraine (migraine headaches that occur exclusively during menstruation). Heredity plays an important role, with 70-90% of migraneurs reporting a family history of migraine.
In recent years, research involving the role of serotonin, the trigeminovascular system and calcium channel abnormalities in cerebral vasculature has greatly contributed to our understanding of migraine pathogenesis; the previously used terms, “classic migraine” and “common migraine” are no longer felt to be accurate and should not be used. Diagnostic criteria and classifications for all types of migraine headache were established by the International Headache Society in 1988.3 The most common forms of migraine seen in the outpatient setting are either migraine with aura (formerly called “classic migraine”) and migraine without aura (previously called “common migraine”). Of the two, the most common is migraine without aura, occurring in 80% of all migraines.
Clinical characteristics
The specific diagnostic features of migraine with and without aura are listed in Table 2. The clinical features of migraine have been divided into 5 phases, and an attack may consist of anywhere from one to all of the phases.
Phase One: Prodrome
The prodrome usually occurs 12-24 hours before the migraine attack and involves a wide variety of manifestations such as food cravings, mood fluctuations, speech difficulties, mild cognitive defects and speech difficulties, difficulty concentrating, and excessive yawning. As many as half of all migraineurs experience prodromal symptoms but they are often subtle and not mentioned by the patient during history taking.
Phase Two: Aura
The aura occurs in only 20% of all migraine attacks and is usually visual, in the form of flashing lights (photopsia), shimmering zig-zag lines or areas of visual field loss (scotomata). Other variants of the aura include somatosensory or motor disturbances such as numbness, tingling or hemiparesis and are often misdiagnosed as transient ischemic attacks or seizure disorder. Aura symptoms typically develop gradually and occur 20-60 minutes before the headache. They are felt to represent transient cortical dysfunction and are associated with a reduction in cerebral blood flow.
Phase Three: Headache
A typical migraine headache is throbbing, aggravated by movement, is usually unilateral and by definition, lasts at least four hours and can continue for days. The pain may be bilateral and non-pulsatile (in these cases the Valsalva maneuver may produce a pulsating quality). In 90% of attacks there is accompanying nausea and delayed gastric emptying. Although the headache is typically associated with photophobia and phonophobia, neither may occur and do not necessarily need to be present in order for the diagnostic criteria for migraine to be met (see Table 2).
Phase Four: Resolution
During this phase, pain diminishes, as do the other associated symptoms.
Phase Five: Postdrome
Also referred to as the recovery phase, the postdrome occurs after the headache has ended and lasts as long as 24 hours. During this phase, patients may experience significant fatigue or may develop mild euphoria.
Pathogenesis
The exact pathophysiology of migraine is still not known although over the past decade studies of changes in cerebral blood flow during an attack, and research involving the effects of prostaglandins, estrogen levels, the neurotransmitter serotonin and specific serotonin receptors have lead to changes in current understanding of the process as well as in pharmacologic management. Current theory involves a “migraine generator’ located in the brainstem. It is believed that migraineurs have a genetically lowered threshold for migraine and that when exposed to a potential trigger, that threshold is exceeded, ‘turning on’ the migraine generator. The migraine generator activates the trigeminovascular system, causing release of vasoactive neuropeptides which results in cerebral vasodilation, plasma extravasation and degranulation of meningeal mast cells. This is referred to as a sterile or neurogenic inflammation.
Conduction along trigeminal neurons transmits nocioceptive information towards higher brain centers, producing the nausea, malaise, and phono/photophobia of migraine, and further propagates the inflammatory response. Inhibitory as well as excitatory serotonin (5HT) receptors in the brain are implicated in the mechanism of migraine, specifically the 5HT-1B receptor sites located on cerebrovascular smooth muscle, and 5HT-1D receptor sites on trigeminal nerve endings.
Etiology
A migraine may occur spontaneously with no apparent reason, but quite often occurs in response to known triggers. Common triggers for migraine include environmental factors (loud noise, strong odors, bright lights, weather changes), tyramine containing foods (red wine, nuts, aged cheese, chocolate), sulfites (shrimp, pre-packaged salads/salad bars), nitrites (processed meats, medications containing nitrites), monosodium glutamate (Chinese food, meat tenderizers). Hormonal triggers involve fluctuating estrogen levels and a migraine may be triggered by ovulation, oral contraceptives, menses, or the initiation of estrogen replacement therapy. Other triggers are related to lifestyle, such as stressful events, overexertion, fasting or dieting, excessive sleep, anger or depression.
Eliciting a history of known triggers can be quite helpful as identifying and avoiding these triggers wherever possible is an important component of migraine management.
Evaluation
As in other headache syndromes, the history and physical are important in ruling out serious underlying organic disorders. The diagnosis can then be comfortably established if the symptoms meet the diagnostic criteria for migraine. There are no specific laboratory studies that are diagnostic of migraine.
Management
The goals of migraine treatment are to:
1. Eliminate headache pain
2. Eliminate the associated migraine symptoms
3. Decrease the frequency and severity of subsequent attacks
Therapy is directed at either the acute attack (abortive treatment) or preventing recurrence (prophylaxis) and may involve non-pharmacologic as well as pharmacologic modalities. In choosing treatment, the clinician must remember that the effectiveness of any oral agent is impaired due to the significantly decreased gastric motility associated with a migraine attack. Ideally the drug chosen will have a rapid onset of action and high efficacy; the side effects and problems associated with prolonged treatment are important considerations as well. Agents used for migraine therapy are grouped as follows:
1. Over-the-counter (OTC) medications: aspirin, acetaminophen
2. NSAIDS
3. Combination medications: isometheptene/dichloralphenazone/acetaminophen (Midrin), caffeine/acetaminophen/aspirin (Excedrin Migraine), acetaminophen/caffeine/butalbital (Fioricet)
4. Narcotics, opioids
5. Antiemetics (in combination with an analgesic): metoclopramine, prochlorperazine
6. Ergotamine and ergot derivatives
7. Selective 5HT-1 agonists (“triptans”)
8. Prophylactic agents
The step-wise approach to migraine management involves starting treatment with the “simplest” therapy, and if this is not successful, introducing the agent in the next category, continuing down the list above in a trial and error fashion. This approach is not cost effective, requiring the purchase of many different agents. The patient whose pain is not adequately relieved often takes increasingly frequent doses of medication in an effort to obtain relief, increasing the risk of drug rebound headache and likelihood of side effects associated with chronic use.
A more useful approach is to tailor the treatment according to the clinical presentation of the headache. The migraine should first be characterized according to its frequency and severity. A moderately severe headache impairs activity, while a severe migraine refers to an attack that requires bed rest. Frequent is defined as more than 3 attacks per month or more than 5 days of disability per month. Treatment is then chosen accordingly:
· Mild, infrequent migraines: respond well to OTC migraine medications, combination medications and NSAIDS (with or without antiemetics).
·
Mild, frequent migraines: as above, but combination medications containing mild
sedatives (butalbital, dichloraphenazone) are always to be avoided when
treating any frequent headache. Prophylaxis
should be seriously considered.
·
Severe but infrequent migraines:
these are best treated with the selective 5HT-1 agonists (triptans).
Other options (in decreasing order of desirability) include
dihydroergotamine nasal spray, ergotamines, analgesics in combination with
antiemetics.
·
Severe and frequent migraines:
the treatment of choice is subcutaneous sumatriptan.
Other options (again, in decreasing order of desirability) are
sumatriptan nasal spray, DHE nasal spray, other 5HT-1 agonists, and analgesics
with antiemetics. Ergotamine use is
contraindicated due to the significant risk of rebound headache and ergotism. Narcotics and sedatives are not to be used at all.
Prophylactic therapy is necessary.
Over-the-counter (OTC) medications
Simple OTC analgesics such as acetaminophen or aspirin are not specific for migraine. Acetaminophen raises the threshold to painful stimuli, thereby exerting an analgesic effect against all types of headache. These agents are rarely effective as monotherapy for any but the mildest of migraines and will not effectively treat any of the associated migraine symptoms. Bear in mind that inadequate analgesia leads to increasing frequency and quantity of medication used, and that the analgesic rebound headache syndrome occurs with frequent use of any analgesic, even acetaminophen.
NSAIDS
Long acting NSAIDs such as naproxen can offer effective treatment of mild, infrequent migraines. For treatment of mild but frequent migraines, this class of drug is less optimal due to the side effects associated with chronic NSAID use as well as the risk of rebound headache. For patients in whom the use of triptans or ergots is contraindicated, the use of a long acting NSAID in combination with an antiemetic such as prochlorperazine or metoclopramide can be quite effective
Combination medications
Most combination medications used in migraine treatment contain a vasoconstrictor (caffeine or isometheptene), mild analgesic (aspirin or acetaminophen) and a mild sedative (dichloralphenazone or butalbital). Despite the lack of controlled trials that demonstrate efficacy for any of these preparations, with the exeption of Excedrin Migraine (aspirin/acetaminophen/caffeine), their use is widespread. These agents give excellent results in mild to moderately severe migraine, but can produce significant sedation. They must be used judiciously and sparingly, given the risks of dependence, and are never to be prescribed for patients with more than two migraine attacks per week.
Narcotics and opioids
The side effect profile of these agents and the development of effective, migraine specific abortive therapy (selective 5HT-1 agonists) precludes the use of these agents even for severe migraines unless there are clear contraindications to all other therapeutic agents. In doses high enough to produce adequate analgesia for severe migraines, sedation and nausea is quite common. It is inappropriate to use these agents as monotherapy and their use has become less common.
Antiemetics
Used alone, the antiemetics (metoclopramide, prochlorperazine) are not of much use as they do not provide pain relief. However, they are effective in combination therapy, alleviating the nausea and vomiting that typically accompany a migraine, and improving absorption of oral analgesics. Their use in frequent migraine is problematic given the side effects associated with chronic use. This problem is more pronounced in the geriatric population.
Ergotamine and ergotamine derivatives
These agents are potent vasoconstrictors that have activity at serotonin (5HT) as well as dopaminergic receptor sites. The lack of site specificity accounts for many of the ergot-associated side effects. Ergot use results in significant nausea, and although they are very effective agents, major side effects and precautions limit their use. They are contraindicated in pregnancy, coronary, cerebral or peripheral vascular disease, hepatic or renal insufficiency. They are not effective unless given at the very beginning of the headache phase, and quite commonly produce nausea as well as severe myalgias, chest pain. There is significant risk of rebound headache if used more than twice a week, as well as ergotism (gangrene of the extremities).
Dihydroergotamine (DHE), an analogue of ergotamine, is available in parenteral form and nasal spray. There is no rebound headache, but the contraindications to use are the same as for ergotamine and it, too, is a potent vasoconstrictor. Of all the migraine specific abortive agents, it has the lowest recurrence rate.
Selective 5HT-1 agonists (triptans)
This new class of abortive migraine therapy is the only medication that offers effective monotherapy for migraine, due to specific activity at 5HT-1B and D receptor sites. Unlike ergots, they are effective at any time during the migraine attack. These agents cause presynaptic inhibition of sensory nerves, blocking impulse transmission in trigeminovascular neurons, neuropeptide release and resulting in vasoconstriction of meningeal blood vessels. This halts neurogenic inflammation, promotes normalization of vessel caliber, and results in resolution of pain as well as migraine associated symptoms. These drugs are contraindicated in patients with coronary artery disease, Prinzmetal’s angina, recent (within 2 weeks) MAOI use, uncontrolled hypertension, use of ergots within 24 hours, known hypersensitivity to any of the triptans, or basilar or hemiplegic migraine.
For patients with underlying risk factors for CAD, triptans may be used only after a complete cardiovascular work-up has been completed. In all cases of myocardial infarction and death reported in the literature, the drug was administered in the presence of clear contraindications to triptan use or in patients with cardiovascular risk factors in whom no work-up was done. When used as indicated, the triptans are without significant adverse effect. All of the triptans can produce transient symptoms such as flushing, chest or neck tightness, sensation of lightness or ‘floating’, and burning at the injection site in the case of sumatriptan. They do not represent any serious underlying dysfunction and usually resolve within 5 minutes. The chest tightness may be the result of esophageal muscle spasm, but this has not been definitively proven, and large studies do not show EKG, angiographic or PET scan evidence of myocardial ischemia related to these triptan associated symptoms.
The most widely used triptan, sumatriptan, has been in use since 1993 and has been extensively studied. It is the only triptan available in 3 formulations – as a nasal spray, in injectable (subcutaneous) and oral preparations. Other, relatively newer triptans include zolmitriptan, naratriptan and rizatriptan. They are available only in oral form. The contraindications are the same across the class, but there are some restrictions specific to certain triptans. In patients taking propanolol, the dose of rizatriptan must be reduced, as is the case with rizatriptan and patients with chronic liver disease. The onset of action of the oral triptans is significantly longer (about 1 – 1½ hours) than that of sumatriptan injectable (10 minutes) or nasal spray (15 minutes) which is an important consideration when choosing acute abortive migraine therapy.
Prophylactic agents
The most commonly used drugs for prophylaxis are beta-blockers. Other commonly used drugs are amitriptylene, methysergide (associated with a significant risk of retroperitoneal fibrosis), divalproate sodium and calcium channel antagonists. There is no single dose or dose range for these medications that has demonstrated superior efficacy to any other dose of the same medication, with a success rate of only 35-40%. Only propanolol, timolol and divalproate sodium have FDA approval for migraine prophylaxis.
Cluster
headache
Cluster headaches are characterized by short-lived excruciating, penetrating pain. Unlike migraine, they are more common in men with a prevalence of <0.5% in men and 0.1% in women, and there is rarely an associated family history of cluster headache. The average age at onset is 27-30 years and the frequency of attacks decreases with age.
Clinical characteristics
The pain of a cluster headache is unilateral, usually behind one eye and occasionally radiating to the jaw, temple, nose or teeth. It frequently occurs during sleep and is of sufficient severity to waken the patient. Cluster headaches last between 15-90 minutes, occurring from 2-10 times a day in periods of about 1-4 months. The headaches then resolve completely until the next cluster period, which can occur at regular intervals months or years later.
During a cluster headache, there may be flushing, conjunctival injection, nasal injection and sweating on the same side as the pain. It is not uncommon for the headache to be accompanied by ipsilateral lacrimation, ptosis and miosis. Only one of these associated characteristics is necessary to make the diagnosis of cluster headache.
Patients with cluster headache are in such severe pain that they are unable to remain still, pacing or sometimes banging their head against the wall.
Pathophysiology
The pathogenesis of cluster headache is not completely understood and is felt to involve dysfunction of vascular or neurogenic mechanisms, specifically, hypothalamic dysfunction affecting the proximal intracranial portion of the internal carotid artery. It is postulated that cluster headache may be triggered by external factors such as alcohol or nitrates.
Evaluation
The diagnosis of cluster headache is usually easy to make due to the classic presentation. Cluster headache is most often misdiagnosed as trigeminal neuralgia, or rarely, patients with chronic paroxysmal hemicrania (discussed below) are misdiagnosed as having cluster headache. To differentiate the two it is helpful to remember that the pain of cluster headache is not triggered by tactile stimuli as it can be in trigeminal neuralgia. Moreover, the pain of a cluster headache lasts far longer than that of trigeminal neuralgia in which the pain is repetitive but lasts only seconds with each occurrence.
Management
Although the pain of cluster headache is so severe that immediate treatment is a priority, the attacks are brief and most resolve before oral agents can take effect. In the past, treatment included ergotamine preparations or inhaled oxygen, but as mentioned previously, there are significant drawbacks associated with the use of ergots. Sumatriptan, a selective 5HT-1 agonist, in injectable formulation, is the only drug in its class to be approved for the acute treatment of cluster headache.
Chronic paroxysmal hemicrania (CPH)
CPH is a rare headache syndrome that can be misdiagnosed as cluster headache. These headaches are more common in women, and are characterized by recurrent periorbital headaches, occurring as often as 14 times a day. The pain is severe, unilateral, located in the region of the eye, forehead and temple and can be associated with ipsilateral nasal congestion, lacrimation, conjunctival injection and ptosis. Unlike cluster headache, in severe attacks of CPH there is nausea and vomiting. An attack may be precipitated by head movements but the pathophysiology is unknown. CPH responds to indomethacin and no other treatment.
Hypnic headache
This headache disorder is rare and found only in the elderly population. Attacks occur once or twice at night and may last as long as one hour. The pain may be associated with nausea, and is bilateral. The cause is unknown. Lithium, taken at bedtime, can be effective as prophylaxis.
Analgesic Rebound Headache
This phenomenon can occur with virtually any medication used to treat headache. Misdiagnosis or undertreatment leads to frequent or excessive use of medication, which leads to habituation, and even more increased use of medication. Paradoxically, adequate pain relief does not occur despite increased use and the pain may worsen. As the analgesic effect of a particular medication wears off, the headache worsens; if the medication is withheld the headache intensifies. Analgesic rebound headache is more likely to occur in the when the physician fails to recognize the need for prophylactic treatment and prescribes only symptomatic therapy, or when the headache is misdiagnosed and inadequate analgesia is prescribed. Other common errors are prescribing combination medications containing mild sedatives to patients with frequent or severe headaches, permitting too many refills without reevaluating the patient, continuing to prescribe potentially habituating drugs despite evidence of habituation, failing to inquire as to the frequency of headache attacks or medication use, and telling habituated patients to decrease medication use without providing any specific guidelines or follow-up. Rebound headache is more likely to occur with daily dosages of any medication even at relatively low doses than with infrequent (1-2 times per week), larger doses of the same medication. To avoid this, attempt to make the correct diagnosis early and consider prophylaxis for those patients with frequent (more that 2 per week) headaches, or very severe headaches in which the patient reports having to take 3-4 tablets or more of any oral medication in a single day. Remember that a very common complaint of patients with chronic headaches is that they have tried every medication that exists and none of them work, and that the main reason for this is that the headache syndrome was misdiagnosed and/or insufficient or inappropriate analgesics were prescribed. Consider referral to a neurologist for a patient who is habituated; depending on the medication, hospitalization may be necessary.
Secondary
headaches
Headaches that are caused by underlying structural or systemic disease are referred to as secondary headaches, and common causes have been mentioned earlier. A detailed discussion of these headaches is beyond the scope of this chapter, but an outline containing information about the three most common (subarachnoid hemorrhage, temporal arteritis and tumor) may be found in a table at the end of this chapter.
Table
1: Danger signals
Consider a serious
cause of headache when the following occurs:
a)
sudden onset new, severe HA “worst ever”
e) progressive HA course
b)
onset HA with sexual activity/physical exertion
f) new onset HA after age 50
c)
HA associated with abnormal neuro exam or fever
g) HA associated with meningeal signs
d)
HA associated with decreased consciousness
h) HA in a patient with a malignancy
or
immunocompromise
A.
At least 5 attacks that fulfill criteria in B, C, D, and E
A. At least 2 attacks that
fulfill criteria in B and C
B.
Headache attacks that last 4 – 72 hours
B. At least 3 of the
following:
C.
Headache has at least 2 of the following:
1. One or
more completely reversible aura
1. Unilateral site
symptoms that indicate focal cerebral
2. Pulsating quality
cortical and/or brain stem dysfunction
3. Moderate to severe intensity
2. At
least one aura symptom develops
4. Aggravation by walking stairs or similar
gradually over
>4 min., or 2 or more
routine physical activity
symptoms occur in succession
D.
During headache, at least 1 of the following:
3. No
aura symptom lasts more than 60 min.
1. Nausea or vomiting (or both)
4.
Headache follows aura
2. Photophobia and phonophobia
C. No evidence of related organic disease
E.
No evidence of related organic disease
Table 3: Characteristics of Migraine, Cluster, and
Tension-Type Headache5
________________________________________________________________________________________________
_________________________Migraine____________Cluster__________Tension-type____________
Onset
Peak incidence in adolescence
30s or 40s
Variable, generally problematic in the
Frequency
1-2 attacks per month, often with
1 or more attacks Episodic
type – less than 15 days
Menses
per day for 6 to 8 20s or beyond
Weeks
Chronic more than 15 days per month
Location
Unilateral>bilateral
100% unilateral;
Bifrontal, bioccipital, neck
generally orbito-
temporal
Description
Throbbing or intense pressure
Nonthrobbing,
Squeezing, pressing, aching
excruciating, boring,
penetrating
Duration
4 to 72 hours, usually 12-24 hours 30
mins to 2 hours,
Episodic-several hrs
Usually 45-90 mins
Prodrome
Changes in mood, energy, appetite
May include brief
None
mild burning in the
ipsilateral inner
canthus or internal
nares
Aura
Up to 60 minutes, usually 20 mins,
None
None
often visual
Associated
Nausea, vomiting, phono and photo-
Ipsilateral ptosis-
Episodic-loss of appetite,
either light or
Symptoms
phobia, sensitivity, occasional ptosis
miosis, conjunctival
or sound sensitivity
Behavior
Retreat to a dark, quiet room
Frenetic pacing, Generally
not affected; may have a mild
(hibernate)
rocking
reduction in functional capacity
References
1. Guidelines for the management of headache. Danish Neurological society and the Danish Headache Society. Cephalalgia 1988; 18:9-22.
2. Neurologic emergencies. Emergency Medicine Clinics of North America. August 1997; 15(3): 507-525.
3. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988; 8 (suppl 7): 1-96.
4. Osterhaus JT, Gutterman DG, Plachetka JR. Healthcare resource and lost labor costs of migraine headache in the United States. Pharmacoeconomics 1992;2:67-76.
5. Marks DR, Rapoport AM. Practical Evaluation and Diagnosis of Headache. Seminars in Neurology 1997; 17(4); 307-312.
6. Ferrari, MD. Migraine. Lancet 1998; 351:1043-51.
7. Capobianco DJ, Cheshire WP, Campbell JK. An Overview of the Diagnosis and Pharmacologic Treatment of Migraine. Mayo Clin Proc 1998; 71:1055-66.
8. Schwartz BS, et.al. Epidemiology of tension-type headache. JAMA 1998; 279: 381-383.