Contact: to feature here

Thread Rating:
  • 1 Vote(s) - 5 Average
  • 1
  • 2
  • 3
  • 4
  • 5
Migraine: Diagnosis and Classification of Headache
Headache is in almost all cultures and countries among the most common health complaint, and was one of the first conditions to be commented on in ancient medical literature. The great majority of headaches requiring medical attention are manifestations of migraine, which is today the best understood of the headache disorders. The many recent advances in understanding of headache physiology, pharmacological treatment of headache and application of biotechnology to the treatment of headache have been mostly in the area of migraine, which also represents most of the historical cases of headache.

Some of the earliest treatment recommendations for headache involved decompressive skull surgery (trepanation) and evidence of such procedures has been found from as early as 7000 BCE.

Quote:The Ebers papyrus from about 1500 BCE contains clinical descriptions of headache syndromes consistent with migraine, and the ancient Egyptians developed an extensive pharmacopoeia of herbal medicines, some of them still recommended for migraine.

Egyptian therapies also included:
  • Rubbing the affected side of the head with a fried fish, which is difficult to reconcile with current headache medicine
  • Binding tightly to the head a clay crocodile containing invocations to the relevant gods.
The latter was reported to be effective for chronic headache, and it is possible that the pressure of the linen strips holding to the vessel had a beneficial effect on tension-type headaches [1].

History of Headaches | Details

Hippocrates and Headache
  • The Hippocratic school of ancient Greek medicine also devoted much attention to headache treatment.
  • The “father of medicine (Hippocrates)” himself described the prodrome of migraine and the nausea and vomiting that is often associated with migraines and sometimes relieves them.
  • Hippocrates also described the visual scotoma and some other manifestations of the migraine aura and observed the correlation between migraine and exercise, including “Immoderate venery”.
    Note: Immoderate venery means: sexual indulgence
Quote:The occurrence of nausea with migraine and the frequent relief of headache with vomiting led Hippocrates to ascribe the disorder to vapors rising to the head from the stomach, which although incorrect was the ancestor of the neurohumoral theory of migraine pathogenesis that predominates today.

Quote:In addition to Hippocrates and his disciples, the philosopher Plato often commented on medical topics. Although he was usually wrong when he opined about medicine, Plato did contribute one observation that is germane to headache treatment and to psychosomatic medicine generally:

he suggested that in some cases head pain was due to excessive preoccupation with the body and its symptoms [2].

Temples of Asklepios | Therapeutic Sleep and Headache aversion
Headaches were among the chief symptoms addressed by the priests at the temples of Asklepios, and were often treated by the Enkoiemesis or induction of therapeutic sleep, probably by opium, followed by a medicinal diet, both of which may have presaged acute pain management and holistic headache treatments of the present day.

Roman Medicine and Headache
The other precursor of the Western medical tradition in classical antiquity was Roman medicine, epitomized by Galen of Pergamon even though he himself was Greek.

Galen took an active interest in headaches, and was the first to use the term Hemicranias, from which “migraine” was derived.
  • He also identified for the first time the meninges and cerebral blood vessels as the source of head pain, and ascribed pulsatile headache with vomiting, particularly marked in children, to the accumulation of bile in the stomach, giving rise to the still-used term, “bilious attacks”.
  • Arataeus of Cappadocia, another Greek physician in the Roman Empire, at about the same time summarized the features of what are today called classical or common migraine, and distinguished three types of headache: generalized cephalalgia, unilateral and usually migrainous hemicranias and cephalea, headache not in a nerve or blood vessel distribution. Arataeus also advocated cauterization of the scalp and scalp muscle division for refractory headache, modern equivalents of which have lately been used in headache treatment [3].
Quote:Hemicranias continua means a persistent unilateral headache, the term from which word  “Migraine” was derived.

The word "migraine" combines the word "hemicranias" (which means half the head) and megrim, which in the 18th century meant low feeling on a whim.

Headache also received attention in eastern medical traditions. The second-century surgeon Hua To identified acupuncture points useful in treating head pain, and according to legend used acupuncture needles to remove a bulging frontal lesion from a patient suffering from pain between his eyes, after which a canary flew out. Other techniques of ancient Chinese medicine used for headache, such as cupping, the application to the skin of heated glass vessels containing a vacuum to remove toxins, and moxibustion, the first direct and later indirect application of heat and herbal remedies to the skin to rebalance qi or life energy, may date from the 16 [th] century BCE, and their principles are reflected today in western energy medicine and detoxification treatments [4].

The ancient Indian Ayurvedic medical tradition, like the Greeks, postulated that disease was caused by imbalance of doshas or humors. The system derived its name from the Sanskrit for “science of life” or “life knowledge”, and from its beginnings approximately 5,000 years ago emphasized individual variations in disease susceptibility and the role of lifestyle and diet in the production of disease. Headache and pain in general was often ascribed to excess of vata, the energy of movement that is often associated with nervous disease. Headache treatment focused on diet and natural remedies, and some of these techniques are applied today in western holistic medicine as well as Ayurvedic practice [5]. The North and South American “Indian” medical traditions are similar in their approach to headache and other nervous disorders, although sometimes different in the herbal remedies used on account of geography, and appear to have used ritual and spirituality as well as natural medications for several millennia before the arrival of Europeans [6].

As in many areas of medicine, the Islamic world preserved and extended some important ancient insights during the western Dark Ages. The 8 [th] and 9 [th] century medical writers Muhammad al-Razi and Muhammad al-Tabari extensively reviewed the writings of Hippocrates and Galen in their books, and Sabet ibn al-Harani wrote a comprehensive pain textbook which dealt with headache at the start of the 10 [th] century. al-Tabari differentiated migraine from other types of headache, presciently ascribed it to vascular inflammation and described two medical methods of treatment as well as cauterizing the temporal artery for focal temporal pain that may have represented arteritis. Ibn Sina or Avicenna described methods for preparing and testing the efficacy of medicine in his influential Canon of Medicine about a century later, and emphasized the role of exercise in disease treatment and prevention [7].

Byzantine treatments for headache began with purging and bloodletting, preferably from the side opposite to hemicranial headache, often copious and from the the cranial circulation by way of incisions in the nose as well as from the arm. The 1500 medical aphorisms of Maimonides include many concerning headache management, particularly bleeding from palpable pulsating vessels, presumably those involved in the pathogenic events of migraine which were to be clarified centuries later. Beginning with Arataeus, these physicians independently developed the technique of cupping that was being used in Chinese medicine. More benign recommendations of the time included the advice of Oribasius, physician and friend to several late western Roman emperors, to inject soft oil into the ear on the involved side, and the 10 [th] century recommendation by ibn Isa to bind a dead mole tightly to the head, recapitulating the ancient Egyptian method [8].

St. Hildegard of Bingen wrote medical texts in addition to being a philosopher, dramatist, composer and Benedictine abbess. She experienced scintillating visions that are now felt to have been ocular migraines, and described these in writing as well as with drawings that remain classic illustrations of migrainous aura. Her medical works do not reflect her visionary experiences but result from her extensive experience in her abbey’s medicinal garden, and as one of few women schooled in Latin in that day, she was able to write about herbal medicine in a way that most of the women who mainly practiced it at that time could not, and provided the basis for subsequent compendia of medical herbalism. A particular innovation in her recommendations was the application to the scalp of poultices soaked in vinegar and impregnated with opium; it is thought that the vinegar opened the pores of the scalp and facilitated the absorption of the opium [9].

Headache came under the purview of “neurology” when Thomas Willis introduced that term in 1672, and proposed that migraine was the result of cerebral vasodilation, and suggesting that migraine symptoms were correlated with slowly ascending spasms beginning in peripheral nerves and extending centrally. Erasmus Darwin, grandfather of Charles, proposed at the end of the 18 [th] century that patients be spun in a centrifuge in order to redistribute blood from the head to the feet to reduce cerebral vasodilation and head pain. More detailed headache classification was attempted during the 18 [th] century, with the first description of what was later called cluster headache given by van Swieten in 1745, and the differentiation of primary or idiopathic headache from symptomatic headache secondary to an identificable cause and the delineation of 84 headache syndromes by Baur in 1787 [10]. The distinction between migraines with prodromal symptoms, usually visual (migraine ophthalmique), and those without ( migraine vulgaire) was first proposed in 1887 by Louis-Hyacinthe Thomas, by profession a librarian but also a migraineur with keen observational powers [10].

While developing his system of homeopathic medicine in which substances causing a particular symptoms were used in great dilution to cure it, Samuel Hahnemann found that many vasodilatory compounds such as nitroglycerin (Glonoinum) were effective homeopathic remedies for migraine. This supported the predominant vascular theory, but that concept was challenged in 1863 by Edward Living’s treatise on “Megrim and Sick Headache”, which suggested that these represented brain dysfunction due to “nerve storms” that were related to epilepsy. Gowers’ first comprehensive English neurology text in 1888 endorsed this neu1rogenic view, and differentiated between intermittent treatments aimed at aborting attacks and continuous treatment intended to prevent them. He introduced the “Gowers solution” of nitroglycerin in alcohol that was one of the first examples of vasoactive therapy, along with the alkaloid of the ergot fungus that was first used in 1868. Gowers also advocated prophylactic treatment with Cannabis indica, presumably having a neural effect [11].

Headache research became more active and systematic in the 20 [th] century, beginning with the isolation of the therapeutically active ergot ingredient (ergotamine) in 1918 and the demonstration by Wolff and colleagues that the migraine aura corresponded to extracranial vasoconstriction and the headache to vasodilatation. The demonstration in 1941 that blood vessels and meninges were pain-sensitive but the brain itself was not supported the vascular theory, while Lashley’s description of his own migrainous scotomata in 1941 and the identification of cortical spreading depression by Leão in 1944 put in place crucial supports of the present view of the neural origin of migraine. The discovery of serotonin and the effects of a variety of serotoninergic drugs, particularly the demonstration in 1959 of the efficacy of methysergide against migraine, indicated the relationship between a particular neurotransmitter and what were still often called vascular headaches, and it became clear during this period that the correspondence of vasoconstriction with aura and vasodilatation with headache was not sufficient to explain migraines entirely. Spreading cerebral oligemia was demonstrated in migraine with aura by newer methods for measurement of cerebral blood flow in 1981, and oligemia was correlated with cortical spreading depression in animal models the following year. This led to the combination of the vascular and neurogenic theories in 1987 in order to explain migraine on the basis of “neurogenic inflammation”. This is the present consensus, and positron and functional MRI imaging has led to the identification of a probable brainstem migraine generator that sets this in motion. Recent interest has focused on the possibility that migraine may represent an ion channel disorder (channelopathy), and on the role of calcitonin gene-related peptide (CGRP) in the initiation of migraine attacks, while the identification and characterization of serotonin receptors has led to the development of sumatriptan and a dramatic expansion of the armamentarium for effective headache treatment [12].


Migraine, which represents about 85 per cent of headaches requiring medical attention , and is ranked 19 [th] among diseases causing disability throughout the world by the World Health Association. In the United States, migraine is thought to affect about 30 million people, many of whom do not seek medical attention for this. The disorder is a particular source of impaired domestic function and workplace productivity, as it predominates during the productive years of 25 to 50, and is 3 times as common in women as among men. A recent study estimated that medical costs for migraine evaluation and treatment approach 2 billion dollars annually, while 13 billion dollars in productivity are lost on account of migraine.

As mentioned earlier, it was suggested in ancient times that the pain of migraine arose from the meningeal coverings and blood vessels of the brain. Harold Wolff elaborated a vascular theory of migraine in the 1940s, based in part on his personal experience with the disorder: he was apparently in the habit of massaging his temples, particularly when he felt the prodromal symptoms of a migraine attack, and noticed that the usually palpable temporal pulse disappeared when he was having a migraine aura but was bounding during the migraine itself, and coincided with the pulsing headache that he experienced. As the technique of cerebral angiography was more frequently used for headache evaluation, constriction of arteries was suggested before the onset of headache, while dilated vessels were seen during the migraine attack. Although most of the brain is insensitive to pain, its blood vessels are richly supplied with pain-sensitive nerve fibers. It was therefore suggested that constriction of the cerebral blood vessels and reduction of cerebral blood flow caused symptoms of migraine aura such as numbness, tingling or visual disturbance, and then led to compensatory dilation resulting in headache, either from edema or inflammation around the affected blood vessels that activated the surrounding nerve fibers [14] . This theory explained the initial premonitory symptoms and subsequent pulsatile headache of the migraine attack, as well as the effectiveness of caffeine, ergotamine and other therapies that constrict blood vessels. Two problems remained, however: most migraine sufferers do not have auras before their attacks, and newer methods of measuring cerebral blood flow have not shown the expected decrease in blood flow during pre-migraine symptoms and increase in blood flow with headache in those who do [15].

These problems and the increasingly-recognized association between migraine and central nervous system conditions like epilepsy and mood disorder have led to a neural theory of its cause. The experimental psychologist Karl Lashley suffered from migraine preceded by one of the most common auras, slow progression and then resolution of decreased vision, and in 1941 carefully mapped his visual loss and suggested that it represented slow inactivation spreading over his visual cortex at a rate of 3 to 5 mm per minute. Two years later, the Brazilian neurophysiologist A. A. P. Leão observed waves of neural hyperactivity followed by suppressed activity moving across the rabbit cerebral cortex at 3 to 4 mm per minute, and termed this “spreading depression”. It was suggested a decade later that the slowly-evolving migraine aura might be due to slowly-progressing spreading depression of the cerebral cortex, preceded by increased neural activity during the migraine headache [16].

The most prevalent view of the cause of migraine today is that genetically susceptible people may have or develop generator sites in the hypothalamus or brainstem (the periacqueductal gray matter of the midbrain) that cause or accentuate waves of spreading depression that may inactivate areas of cerebral cortex and cause auras. The rapid neural firing that occurs at the start of spreading stimulate the release of substances which cause a cascade of inflammation, dilation of cerebral blood vessels and activation of the autonomic nervous system. This makes nerve fibers, particularly branches of the trigeminal nerve which supplies the face and head, more sensitive to pain, and can result in nausea, vomiting and other associated symptoms of migraine. Spreading depression is attended by opening of potassium channels and outward flow of potassium, with a compensatory inward flow of sodium through sodium channels. The associated excitation of neurons results in the inflow of calcium through calcium channels and release of the excitatory transmitter glutamate. The increased neuronal activity also affects the release and reuptake of serotonin. This sequence of events would explain why migraine may be prevented by drugs which affect sodium and potassium channels and glutamate (anticonvulsants), medications which influence serotonin reuptake or bind to serotonin receptors (antidepressants and the migraine-specific triptans) and calcium channel- blocking drugs, as well as those which constrict cerebral blood vessels (ergots) [17].

The susceptibility to migraine is clearly inherited, but the inheritance is complex, with several genes and multiple other factors probably involved. Cortical spreading depression may be due to the abnormal function of ion channels in the cell membranes of neurons, and a number of rare “channelopathies” have been found, causing muscle disorders, seizure disorders, periodic paralysis and some forms of migraine. Familial hemiplegic migraine (FHM) causes migraine headaches with paralysis and is an autosomal dominant disorder (the gene is not carried by the sex chromosomes, and more or less everyone who inherits the gene gets the disorder): attacks of FHM are very similar to some kinds of migraine aura, and 3 causative gene mutations have been identified that result in malfunctioning sodium, potassium and calcium channels [18]. When more than one gene may be involved and the disorder in question is not dominantly inherited, so that some family members will have the gene but not have the disorder, the traditional genetic studies cannot be done, and this is the case for garden variety migraine, particularly migraine without aura. Such disorders can now be studied because the human genome has been essentially deciphered: the Human Genome Project completed the sequencing of human DNA in 2003, and the International HapMap project identified the common patterns of human genetic variation around 2005. The genomes of people with various diseases can be scanned with various markers and compared to the genomes of people without those diseases, in order to identify genetic variants that may be associated with the disease of interest. This is termed a genome-wide association study, and such studies in migraine have suggested 3 genes that regulate the excitatory neurotransmitter glutamate and one that codes for a protein involved in pain perception [19].

It is still uncertain how the molecular alterations of migraine result in inflammation and headache, but it may develop as follows. Cortical spreading depression, responsible for migraine aura, activates pain receptors (nociceptors) such as the protein described above, and this causes the release of chemical factors which dilate blood vessels and initiate inflammation. The trigeminal nerve, subserving sensation in the face and head, is particularly sensitive, and becomes more so as an attack progresses (“central sensitization”). Activation of trigeminal nerve C-fibers, the type which primarily transmit pain, results in the release of substance P (for pain), which causes aggregation of platelets and release of serotonin and thromboxane A2. Clumped platelets, serotonin and thromboxane then activate the production of prostaglandin and kinins (“neurogenic inflammation”) and result in the swelling of the brain’s dural lining, which stretches the pain-sensitive nerve fibers that surround the dural blood vessels and result in the characteristic throbbing pain [20].

Article continues below...
About Author:

Miles E. Drake
Ph.D., M.D

A.B.- Harvard University
M.D.- Duke University School of Medicine

Professor emeritus (1982 to 2007) -Ohio State University College of Medicine and Public Health
Lecturer (2007-2013) - AGU School of Medicine

A comprehensive headache classification scheme has been developed and twice revised by the International Headache Society [21]. The diagnosis of migraine requires at least 2 of the following features: unilateral location, throbbing character, moderate-to-severe pain and worsening of pain by routine activity. There must also be nausea and/or vomiting, hypersensitivity to light and sound (photophobia and phonophobia) or both. A 3-question screen for migraine (ID-Migraine) has been validated in a large group of previously-diagnosed migraine patients: migraine was identified by headache limiting activity for a day or more in the past 3 months, headache accompanied by nausea and headache with photophobia [22].

Tension headache has long been ascribed either to psychological stress or abnormal muscle contraction, but there is often little evidence of either muscle or psychic tension. It is characterized by at least 2 of the following: nonpulsatile pressing or tightening pain, mild-to-moderate intensity and bilateral location. There must be no nausea or vomiting and no photophobia or phonophobia [23]. Cluster headache, which has a unique male preponderance (3:1), is increasingly referred to as trigeminal autonomic cephalgia because the pain is located in the sensory distribution of the trigeminal nerve over the face, and because tearing and other signs of autonomic nervous system dysfunction are part of the syndrome. Its diagnosis requires at least 5 attacks, occurring between 1 and 8 times on a given day, of extremely severe unilateral (infrequently bilateral) pain around the orbit or in the temporal region, lasting for 15 to 180 minutes. The pain must be accompanied by at least one of the following symptoms on the same side: lacrimation, rhinorrhea, nasal congestion, sweating, dilated or constricted pupil or edema of the eyelid [24].

Migraine is subdivided into two major categories and several infrequent variants. At one time a distinction was made between “classical migraine”, with premonitory neurological symptoms, and “common migraine”, which is much more frequent and lacks the preliminary symptoms. Common migraine has been rechristened Migraine without Aura (MO), and classical migraine is referred to as Migraine with Aura (MA). Several kinds of recurrent attacks in childhood are thought to be migraine equivalents, and may be precursors of more typical migraine in adulthood (periodic syndromes). A small number of patients have only visual symptoms in one eye (retinal migraine). Other migraine variants include chronic migraine (migraine present more than half of the time), status migrainosus (continuous migraine for 72 hours or more), persistent aura without infarction (a prolonged migraine aura without neurological signs of stroke), migrainous infarction (stroke in association with a migraine attack) and migraine-triggered seizures (the overlap of migraine and epilepsy) [25].

MO consists of recurrent headache attacks lasting 4 to 72 hours without focal neurological symptoms. Headaches are typically unilateral, pulsating, moderate-to-severe in intensity, and aggravated by routine activity. They are associated with photophobia, phonophobia, nausea and vomiting. MA is characterized by recurrent focal neurological symptoms (auras) that develop over 5 to 20 minutes and last for 60 minutes or less. These are usually followed by a usually unilateral, pulsating, moderate-to-severe headache that is aggravated by physical activity and accompanied by nausea, vomiting, photophobia and phonophobia in various combinations, although the headache may lack some of these features and may be mild or absent. The most common auras are visual, and consist of a scotoma (blind or dark spots in the vision of one eye, a curtain slowly drawn across one eye or slowly-moving spots), scintillating scotoma (shimmering, often curved patches of obscured vision, sometimes associated with tunnel vision), fortification spectra (zigzag lines), a kaleidoscope effect, flashing lights or bright blobs, oscillopsia (vibration of objects) or metamorphopsia (alteration of objects, usually in size). There may also be temporary blindness in one or both eyes. Auditory changes are less frequent, and involve hallucinations, modulation of the pitch or intensity of sounds, or tinnitus. Alterations in smell or taste, unilateral weakness or paralysis, unilateral sensory loss or paresthesias, sensations that limbs or teeth are growing or changing or have become separated from the body, autonomic symptoms (nausea, sweating), speech and language disturbances (aphasia, dysarthria) and mental or emotional symptoms are occasional auras. These are sometimes encountered before seizures also, and are among the chief evidence for the overlap of migraine and epilepsy [26].

Migraine in childhood may take other forms in addition to or instead of headache. Periodic syndromes, which are recurrent and stereotypical in the individual patient, may be “migraine equivalents” or the precursors of more straightforward migraine in adulthood. The attacks usually involve nausea and vomiting, usually with pallor and lethargy, and symptoms resolve completely within hours. Cyclical vomiting, recurrent abdominal pain without evident cause (abdominal migraine) and recurrent vertigo without other symptoms (benign paroxysmal vertigo of childhood) are the most common forms. Although motion sickness is very common in childhood, repetitive episodes of this or sleepwalking may all be childhood precursors of migraine. The diagnosis is based on history and possibly headaches at other times or family history of migraine [27].


Another important classification of headaches is primary versus secondary. Primary headaches, epitomized by migraine, are recurrent disorders of cerebral function for which no underlying structural cause can be found. Secondary headaches are much less frequent, and are due to some brain lesion or medical disorder, exemplified by the brain tumor or aneurysm that many headache patients fear. This distinction is important because of the ubiquitous question of whether imaging studies should be performed in headache patients. Incidental and insignificant imaging changes may be discovered in patients with benign headache disorders, and cost concerns are growing in American and other healthcare systems; on the other hand, missing the diagnosis of a brain tumor is the most common cause of malpractice litigation against neurologists in the United States [28].

Several studies have looked at the incidence of MRI abnormalities in the general population, and have found arachnoid cysts, tumors and arteriovenous malformations too small to warrant neurosurgical attention, type I Chiari malformations of the cerebellum, clinically silent cerebral infarcts and white matter lesions related to head trauma or aging in up to 7 per cent. A very large meta-analysis found brain tumors in less than 1 per cent of normal subjects and non-neoplastic changes in 2 per cent while a large Dutch study found 1 per cent with tumors, 1 per cent with vascular lesions and 7 per cent with small strokes, all unaccompanied by symptoms . Several additional studies have looked at MRI and CT imaging in chronic headache patients with normal physical examinations: insignificant changes or normal variants of brain structure were found in up to 28 per cent of CT scans and 46 per cent of MRIs, while between 0. 5 and 0. 9 per cent had brain and pituitary gland tumors, aneurysms or arteriovenous malformations, less than half of which required neurosurgical attention. Imaging studies, particularly MRI, in neurologically normal patients with recurrent headaches are thus more likely to yield incidental or insignificant findings than to identify causative lesions [29].

Headache patients with “red flags” that suggest a secondary rather than a primary cause are generally conceded to need imaging studies. These include headache of new onset, abrupt change or worsening of headaches, headache of progressive severity, patients with abnormal neurological examination, headaches that change with head position or are exacerbated by exertion and that are worsened by the Valsalva maneuver (sneezing, coughing, straining). The likelihood of a structural cause for tension headaches as described above is essentially nil, and imaging studies are not felt to be warranted. Cluster headaches (trigeminal autonomic cephalgia), on the other hand, not infrequently indicate a pituitary lesion or thrombosis of the cavernous sinus, and brain imaging is warranted [30].

There has recently been much discussion of whether patients with migraine have an increased risk of cerebral infarcts, and whether MRI is warranted for that reason. One study in the Netherlands found no difference in the incidence of clinically silent vascular lesions between migraine patients (5 per cent) and normal controls (8 per cent), but the likelihood was greater in patients with frequent migraine attacks and migraine with aura than in those with uncomplicated migraine, particularly among women . Apparent infarcts in the brainstem and cerebellum were more common in migraine with aura (7. 5 per cent) than migraine without aura (2. 2 per cent) or normal controls (0. 7 per cent) in another Dutch study, and similar findings were reported among migraine patients in Iceland. Follow-up of the Dutch patients over 9 years showed no further MRI changes despite continued migraine, so they were not specifically correlated to the patients’ symptoms. For this reason, it has been suggested that, although patients with migraine may need attention for increased stroke risk, especially women who smoke and take contraceptives, imaging studies are not helpful in this regard [31].

Since migraine predominates among women of childbearing age, a correlation with reproductive stages and menstrual cycle is not unexpected. More than 50 per cent of women with migraine will have them more often or more severely in relation to menstrual periods, and 7 to 14 per cent of women with migraine have them only during menses, termed menstrual migraine. Attacks occur most commonly during the 2 days before onset or during the first 2 days of the period in at least 2 of 3 menstrual cycles, and are similar in characteristics to other migraine attacks but tend to be more severe, longer-lasting, more frequent and more resistant to traditional therapy. Fortunately, menstrual migraine is responsive to acute treatment with triptans. Oral contraceptives and hormone replacement therapy may increase the frequency and severity of menstrual and other migraine. In addition, migraine with aura increases the risk of stroke, and the combination of migrainous aura, contraceptives and smoking is a source of particular risk. It is important for all practitioners involved with women’s health to identify migraine and migraine with aura in particular, and to assess carefully the appropriateness of oral contraception or hormone replacement therapy and advocate vigorously for smoking cessation in such patients [32].


One important aspect of migraine treatment is the identification and management of inducing and aggravating factors. Many if not most migraine patients have “triggers”, but they vary so greatly between individuals that they cannot be systematically addressed. Physiological factors (stress, fatigue, sleep deprivation or excess, menses, time-zone shift, barometric pressure), chemical influences (smoking, hormonal therapy and other medications, scents and perfumes) and dietary triggers (food containing tyramine, alcohol, monosodium glutamate, nitrates, coffee consumption and withdrawal) should be identified and avoided or managed, but lifestyle adjustments should not be more onerous than the headaches. These problems are important manifestations of the crucial nursing role in history-taking and education with headache patients. [33].

Migraine therapy may be divided into symptomatic, intermittent prophylactic and chronic prophylactic treatment. Symptomatic treatment, also referred to as acute or abortive, is only taken during an attack, with the goal of terminating the attack or alleviating symptoms. The medications used may be specific or nonspecific: the former are effective against all of the manifestations of migraine (headache, nausea, vomiting, prostration) while the latter work primarily on headache pain. Acute or abortive treatments can also be divided according to severity of the attack, with nonspecific agents more useful for mild-to-moderate migraine and specific therapies preferable for moderate-to-severe episodes, although opioid pain medications are currently recommended for the most severe attacks only. Mild-to-moderate migraine is most often treated with over-the-counter analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs). The former include aspirin, acetaminophen, ibuprofen and naproxen sodium. These are not FDA-approved for migraine, although naproxen-sumatriptan combinations are approved by the FDA, but are inexpensive and largely free of adverse effects unless the maximum dosage is exceeded (4000 mg per day for aspirin and acetaminophen, 2400 mg daily for ibuprofen and 660 mg naproxen a day). NSAIDs appear to reduce neurogenic inflammation by inhibiting the enzymes cyclooxygenase and lipooxygenase and reducing the production of inflammatory prostaglandins. Aspirin or acetaminophen can also be combined with caffeine to add a vasoconstrictive effect [34].

Nonspecific prescription agents include the vasoconstricting agent isometheptene and the muscle relaxant dichloralphenazeone added to acetaminophen (Midrin). Gastric upset with NSAIDs, or GI bleeding at higher doses, can be minimized by postprandial dosing when possible, enteric-coated preparations or the addition of antiemetic drugs such as metoclopramide (Reglan) or domperidone (Motilium), which increase gastric motility and enhance the absorption of other drugs, and can also prevent the nausea associated with migraine. Opioid analgesics should not be used as first-line therapy, but are the safest options during pregnancy and are safest when patients have infrequent attacks that respond promptly, have difficulty tolerating other acute migraine therapies, and have no evidence of dose escalation or overuse [35].

Excessive use of symptomatic medication can result in transformation of episodic migraine, which is defined as headaches for 15 days or less per month, into chronic migraine, in which headache occurs more than 15 days each month. Prolonged or continuous headache that may lack some migraine features and is unresponsive to abortive treatment (chronic daily headache) may also emerge if patients overuse symptomatic medications. Medication overuse headache can occur if some of these symptomatic medications are taken for other reasons. Headache more than half the time is often an indication for the use of preventive medication, but preventive treatment often will not work if symptomatic medications are also being overused [36].

Moderate-to-severe migraine often needs symptomatic treatment with specific medications, which relieve migraine headache but no other pain. Ergot alkaloids have been used since the 19th century and were initially thought to work by constricting the painfully dilated cerebral blood vessels, but it now appears they work additionally or primarily at the serotonin receptors, particularly the 1B and D types. The triptans have been developed over the last 25 years to act on the serotonin receptors (5-HT1B/1D agonists), and are currently the most effective agents for migraine.

Ergot alkaloids constrict arteries and veins are agonists of the 5-HT1B/1D receptors and also partially stimulate (partial agonists) or in some cases block (antagonists) receptors for norepinephrine, dopamine and tryptamine. This accounts for their desirable effects in migraine, and also for their undesirable effects on coronary arteries and peripheral blood vessels. Ergotamine is given as sublingual tablets or combined with caffeine in tablets or rectal suppositories. Dihydroergotamine can be injected intramuscularly or subcutaneously or taken as a nasal spray. Orally-inhaled ergotamine spray is now under review by the U. S. Food and Drug Administration (FDA). Nausea and vomiting will follow ergot use in 10 per cent of patients, less with nasal spray or suppositories. They are contraindicated in cardiovascular and peripheral vascular disease because of vasoconstriction, and in pregnancy because of the risk of miscarriage from uterine contractions and fetal distress. A “black box” warning has been issued by the FDA, cautioning about life-threatening peripheral ischemia if ergotamine is used along with strong inhibitors of the cytochrome P450 3A4 system that metabolizes many medications in the liver (CYP3A4). Inhibition of CYP3A4 can result in elevated serum ergot levels and vasospasm. The contraindicated combinations include ergotamine plus macrolide antibiotics (erythromycin and its derivatives), protease inhibitors used in HIV treatment and azole antifungal drugs (ketoconazole, etc. ). Overuse of ergot alkaloids (more than 6 mg of injected DHE per week, 3 mg per day of DHE nasal spray, 3 ergotamine tablets a day or 6 ergotamine plus caffeine during an attack) can also cause vasospasm. Because of these complications, ergot alkaloids are recommended only for patients with migraines that are moderate but frequent or infrequent but severe. Only rectal ergotamine is superior to the triptans in efficacy, but the ergots may help with intractable or continuous headache [37].

Multiple triptans are now available, with several additional permutations of combination and route of administration. They are agonists of the 5-HT1B and 5-HT1D receptors, and constrict intracranial blood vessels as well as modulating the release of neurotransmitters from nerve terminals. These actions make them highly and rapidly effective for migraine headache only, and also effective for the nausea and vomiting that often attends migraine. They are equally effective for migraine with and without aura, but are not helpful in migraine prevention and should not be used in patients with cerebrovascular disease, cardiovascular disease, poorly-controlled hypertension or peripheral vascular reinsufficiency because of the rare occurrence of vasospasm. They are not recommended for “ basilar migraine”, with associated symptoms of cranial nerve or cerebellar dysfunction or alteration of consciousness, although it is not certain that their use will precipitate stroke. More practical problems are chest heaviness or constriction after oral dosing or burning at the site of injection with a subcutaneous preparation, paresthesias, flushing, sweating, dizziness and fatigue and drowsiness after administration [38].

Triptans, like other serotoninergic drugs, should not be used in combination with monoamine oxidase inhibitors, or in the case of oral triptans for 2 weeks after they are discontinued. Hardly anyone takes these old antidepressants, however, and the interaction is not significant for subcutaneous injection. The combination of triptans and ergotamine or use of 2 triptans within 24 hours is not recommended because the vasoconstriction they cause could be additive. Triptans should also not be combined with serotonin-norepinephrine reuptake- inhibiting antidepressants (venlafaxine, desvenlafaxine, duloxetine) because of the possibility of serotonin syndrome [39].

There has been great consternation about serotonin syndrome, with symptoms ranging from jitteriness and tremor to hyperthermia, unstable pulse and blood pressure, rigidity, increased reflexes, vomiting and diarrhea, agitation, coma and death, when drugs affecting serotonin are used in combination. The FDA has issued a warning about the concomitant use of triptans and SSRI or SNRI antidepressants, but the American Headache Society has suggested that the risk may be no greater than that of antidepressant use alone [40].

There are no major differences in efficacy or adverse effects between the triptans or between oral, injected or inhaled forms. They begin to act in 10 minutes to 2 hours, and have half-lives of 2 to 6 hours except for one long-acting one (26 hours). They therefore differ in convenience and onset and duration of action, and may have “niches” of certain patient types and problems for which they are preferable. Almotriptan has in many studies the lowest incidence of adverse effects, and may therefore be helpful for sensitive patients. Eletriptan is the newest and most efficacious triptan and has one of the more sustained durations of action, so it is the “big gun” for refractory migraine, but like the ergots is metabolized by CYP3A4 and caution is needed about inhibitors of that system like clarithromycin and ketoconazole. Frovatriptan is less efficacious than other triptans but achieves its maximal concentration rapidly and has the longest half-life, as well as few adverse effects or drug interactions, so it can be taken as partial prophylaxis at times of anticipated migraine risk, such as menses. Naratriptan has high oral bioavailability, so it will begin to act rapidly. Rizatriptan is similarly rapid-acting and useful for patients whose migraine reaches maximal severity quickly. Sumatriptan was the first triptan released, in 1992, and is the “gold standard” to which the others are compared; it is available in oral tablets of 3 strengths, nasal spray, standard injectable form and needle-free injection by compressed nitrogen gas, as well as combined with naproxen for additive efficacy. A transdermal system to infuse sumatriptan with an iontophoretic skin patch is also available. Zolmitriptan is rapidly-acting and has a nasal spray for nauseated patients [41].

The triptans are clearly the most effective treatment for migraine, but they are also the most expensive. A single dose of any of the m in the United States costs approximately $20. 00, and health insurers have sought to control costs by limiting their use. Some insurances and programs have focused upon overutilization of triptans, requiring that they be used in a “step care” algorithm in which treatment intensity is escalated step by step as simpler and less costly alternatives are tried and fail. This is a reasonable approach in many circumstances, but may result in unnecessary pain and disability as patients with severe migraine try various nonspecific headache treatments. An alternative approach is “stratified care”, in which more intensive therapies are initiated at the outset for patients with greater disease severity, even if these are more expensive. Stratified care has been shown to produce better outcomes than step care in migraine treatment [42].

[b]Intermittent prophylactic treatment[/b] is most commonly used when patients have periods in which migraine is much more likely. The most prominent example is menstrual migraine, for which scheduled dosing of long-acting triptans, chiefly frovatriptan, has been found to be effective. Prophylactic treatment involves taking a medication daily to forestall migraine attacks, and principally helps patients with frequent and disabling headaches who cannot take or have not responded to triptans or other acute therapies. One general recommendation is attacks which occur 2 to 3 times per month for 48 hours or more or with significant functional impairment. Others have suggested that preventive treatment be considered when headache frequency exceeds 1 per week. Five drugs have been the subject of class I trials (randomized and including control and treatment groups) for migraine prevention in the United States – propranolol, amitriptyline, valproate, gabapentin and topiramate. A number of other drugs have had Class II trials (control and treatment groups but not random selection), and there have been many Class III (some variables controlled and some not) and Class IV (case studies or series of cases) studies. All of the class I trials have shown efficacy: at least 50 per cent of migraine patients are at least 50 per cent better, and when placebo responders are added in (between 15 and 50 per cent of migraine patients will respond to placebo treatment) as many as 70 per cent of patients are improved. Unfortunately, side effects increase and tolerance develops with decreasing efficacy during a year or more of treatment [43].

Beta-adrenergic blockers prevent cerebral vasodilation and may prevent migraine for this reason. Propranolol and timolol are FDA-approved, while metoprolol, nadolol and atenolol are effective but not approved. Acebutolol, alprenolol, oxprenolol and pindolol have “intrinsic sympathomimetic activity”, and can block and stimulate receptors at the same time; this makes them effective for hypertension and bradycardia, but they are not effective for migraine. Dizziness, fatigue, nausea and depression are occasional problems [44].

Antiepileptic drugs are often effective for migraine prevention. Sodium valprote or divalproex sodium, topiramate and gabapentin have been shown effective in clinical trials. Lamotrigine, leveteracitam, oxcarbazepine, and zonisamide may also be effective to lesser degrees. Because epilepsy as well as anxiety and bipolar disorder, for which some of these drugs are used, are often comorbid with migraine, these agents may be useful despite a greater incidence of adverse effects [45].

Antidepressants affect serotonin release, transport and reuptake, and should therefore have some effect on migraine. Amitriptyline has been shown effective for migraine prevention, but is not FDA-approved. Most other antidepressants have been used with some effect in some patients, but the sedation, weight gain and anticholinergic effects of tricyclic agents and the concerns about serotonin syndrome with SSRI and SNRI agents have limited their usefulness, and they may not be safe in combination with acute use of triptans. The FDA has also cautioned about suicidal ideation with antidepressants, which is an unnecessary risk in migraine prevention [46].

Calcium-channel blockers are modestly effective for migraine prevention. Verapamil has been widely and safely used, and also for cluster headaches. Nimodipine is preferentially active on cerebral blood vessels and was shown to be effective for migraine, but is now limited to inpatient treatment of vasospasm after subarachnoid hemorrhage. Flunarizine is approved for migraine prevention in most European countries but not in the United States. Angiotensin-converting enzyme (ACE) inhibitors, chiefly lisinopril but also Enalapril are supported by open-label studies in migraine prevention but are not FDA-approved or widely-used in Europe or the U. S. [47].

Complementary and alternative medicine is widely used for headache treatment. The substances of principal interest are either herbal substances with anti-inflammatory effect or “metabotropic” drugs that affect cerebral energy production. Feverfew (Tenacetum parthenium), a relative of chamomile, has been used in herbal medicine since classical antiquity, and several controlled trials have suggested at least some improvement in migraine. It subcontains sesquiterpene lactones, chiefly parthenolide, that inhibit serotonin release by platelets, decrease the activation of polymorphonuclear leukocytes, inhibit cyclooxygenase and lipooxygenase and decrease the synthesis of prostaglandins. These actions have an anti-inflammatory effect, and would be expected to reduce neurogenic inflammation and migraine pain. Side effects are few, mostly oral ulcers and allergy. Butterbur (Petasites hybridus) is a member of the daisy family (Asteraceae) with a long history of medicinal use, and also produces antinflammatory sesquiterpene lactones (petasin and isopetasin). It has been studied in several German and American trials: adults and children had significant improvement in migraine frequency and the need for additional pain medications as compared to placebo, with minimal gastrointestinal side effects [48].

Riboflavin (vitamin B2) is involved in the electron transport chain and may enhance cerebral energy production: significant reduction in headache days and migraine frequency were shown in a Belgian controlled trial, with the chief adverse effects being diarrhea, polyuria and urinary discoloration. Magnesium has a variety of effects, chiefly on neuromuscular transmission and central nervous system excitability, and has been the subject of 3 controlled trials, one showing an advantage over placebo in migraine control, one showing no advantage and one showing improvement with both magnesium and placebo. Diarrhea and gastric upset were the chief adverse effects. The combination of feverfew, riboflavin and magnesium also produced headache improvement in both the treatment and placebo groups. Coenzyme Q (coQ10, ubiquinone) is a widely-distributed antioxidant that prevents the depletion of substrates needed to replenish adenosine triphosphate (ATP), which transports chemical energy within cells for their metabolism. Coenzyme Q is frequently used as a nutritional supplement and has been tried at 100 mg per day in a variety of cardiovascular and neurological disorders; this dose produced a significant improvement in migraine, attended by occasional nausea, diarrhea and anorexia. Alpha-lipoic acid, called thioctic acid in Europe, is a fatty acid that enhances energy production by the mitochondria of nerve and other cells and is widely used for health benefits: a Belgian study showed significant reduction in attack frequency, days with headache and migraine severity as compared to placebo, and a study in Saudi Arabia showed an additive benefit from the addition of thioctic/alpha-lipoic acid to topiramate for migraine prevention [49].

Homeopathy , from the Greek for “similar disease”, was widely used in Europe and America in the 19 [th] and early 20 [th] century and remains an important discipline in India and some European countries, but went into sharp decline in the United States until recently. It is still used by up to 20 per cent of French and German physicians and 4 million American adults and 1 million children were estimated to have used homeopathic remedies in 2007. The Greek homeopath George Vithoulkas has shown that homeopathic medicines may alter the vibrational energy of water molecules with which they are mixed, to impart a signal that triggers innate recuperative processes. Remedies generally recommended for migraine and related headaches include Belladonna (deadly nightshade) for sudden pulsatile frontal headaches of rapid onset with flushing and photophobia, Bryonia alba (white bryony) for headache around or over the eyes aggravated by motion and with nausea, Nux vomica (nut of the strychnine tree) for headache triggered by alcohol or sleep deprivation and with phonophobia and nausea, Pulsatilla pratensis (pasque flower) for menstrual headaches or unilateral headaches triggered by food or ice cream, Gelsemium sempervivens (jasmine) for right-sided or posterior headaches relieved by sleep but aggravated by noise or light, Lachesis mutus (Bushmaster snake venom) for similar left-sided headaches Iris versicolor (blue flag) for hemicranial headache with visual symptoms, Sanguinaria canadensis (bloodroot) for stabbing pain beginning posteriorly and involving the eye and Spigelia anthelmia (pinkroot) for burning or pulsating pain radiating into the neck and shoulders [50].

Brain stimulation represents a promising contribution by biotechnology to the treatment of neurologic and psychiatric disorders, and there have been several developments in neurostimulation for migraine. The Vagus Nerve Stimulator, developed for refractory epilepsy, has been approved by the FDA for migraine but not yet frequently used as it involves hospitalization and a surgical procedure for the implantation of a cybernetic device. An electronic stimulator implanted in the chest periodically stimulates the right vagus nerve, uninvolved in respiration, in the neck at a rate, duration and intensity that can be adjusted by the clinician; the patient can also activate the device with a hand-held magnet. Vagal stimulation clearly improves seizure control, and the similarity between epileptic and migrainous auras suggested that the device could be used for migraine. Because there is a strong correlation between migraine and epilepsy, migraine patients were present among the participants in vagus nerve stimulator studies for epilepsy, and their migraines were significantly improved as well. Headache patients were later studied, and small numbers had near-complete alleviation of migraine and cluster headaches [51].

Noninvasive magnetic stimulation of the cranium with a hand-held device has been approved by the FDA for psychiatric disorders, and since migraine is likewise disproportionately represented in this patient population improvement in headaches was soon evident. Significant improvement in migraines was demonstrated in controlled studies, and the FDA has recently approved transcranial magnetic stimulation for this use. A headband-like device for transcutaneous electrical stimulation of the supraorbital nerve in the face has proven very popular with patients and produced significant headache improvement with negligible adverse effects. The latter two devices have been approved in Europe, and are awaiting approval in the United States [52].

Stimulation of peripheral nerves has also been used for relief of refractory migraine. Recurrent stimulation of the occipital nerve at the base of the skull has been shown first in open-label trials and subsequently in controlled investigations to alleviate migraine and also to be useful for cluster headache and intractable cases of neuralgia in the distribution of the occipital nerve. The technique is an outgrowth of the spinal cord stimulator methodology used for intractable back and limb pain, and is thought to modulate the migraine generators associated with the trigeminal nerve through the trigeminocervical complex, a matrix of afferent nerve fibers connecting the caudal trigeminal nucleus with upper cervical spinal levels, chiefly C 2, from which the greater occipital nerve originates. Cylindrical epidural electrodes can be implanted by needle at the C1 spinal level with fluoroscopic guidance, and if done with local anesthesia this will permit preliminary assessment of therapeutic response. Because of the possibility of lead migration and the observation that headache syndromes, unlike neuropathic pain, may require some weeks for therapeutic effects to become evident, more durable attachment of flat and broad paddle electrodes is usually attempted under general anesthesia. The implantable pulse generator has been located in the buttock, thoracic region or low abdomen, and can be activated and the parameters of stimulation adjusted by the patient with a hand-held device. Significant reductions in pain severity, pain-related disability, number of days per month with headache and amount of medication needed for headache relief have been reported in patients with severe episodic migraine, chronic migraine present on more than half of the days each month, cluster headache and a few less common headache syndromes. Patients have tolerated the procedure well, but general anesthesia is usually required and must be repeated when battery replacement is necessary, which may be as often as every year with frequent use. PET scanning and functional MRI inaging has been done in some of these studies, and has suggested that repetitive nerve stimulation induces slow neuromodulatory changes in the central pain matrix that connects the cervical spine, midbrain, thalamic nuclei and cerebral cortical regions [53]. These approaches are very promising for more effective treatment of migraine and other headache disorders in the years to come.


1. Miller N (2005). Walsh and Hoyt's Clinical Neuro-ophthalmology, ed 6. Philadelphia: Lippincott Williams & Wilkins.

2. Borsook D (2012). The Migraine Brain : Imaging, structure, and function. New York: Oxford University Press.

3. Waldman SD (2011). Pain Management, ed. 2. Philadelphia: Elsevier/Saunders.

4. Unschuld, PU (2010). Medicine in China: A History of Ideas, ed. 2. Berkeley: University of California Press.

5. Pole S (2012). Ayurvedic Medicine: The Principles of Traditional Practice. Philadelphia: Singing Dragon Press.

6. Cohen K (2006). Honoring the Medicine: The Essential Guide to Native American Healing. New York: Ballantine Books.

7. Kaadan AN, Jabban HZ, Bankasly A (2015). Migraine in Islamic medicine, Abu Hasan al Tabari (d 360H, 970 AD) as an example. ISHIM Journal, in press.

8. Koehler PJ, Boes CJ (2010). A history of non-drug treatment in headache, particularly migraine. Brain, 133: 2489-2500.

9. Strehlow W, Hertzka G (1987). Hildegard of Bingen’s Medicine. Rochester, VT: Bear and Company.

10. Levin M, Baskin S, Bigal ME (2008). Comprehensive Review of Headache Medicine. New York: Oxford University Press.

11. Tyler KL (2003). Pioneers in Neurology: William Richard Gowers (1845-1915). J Neurol, 250: 1012-1013.

12. Tfelt-Hansen PC, Koehler PJ (2011). One hundred years of migraine research: Major clinical and scientific observations from 1910 to 2010. Headache, 51(5): 752-778.

13. Stover LJ, Hagen K (2006). Prevalence, burden and cost of headache disorders. Curr Opin Neurol 19(3): 281-285.

14. Wolff HG (1963). Headache and Other Head Pain, ed. 2. . New York: Oxford University Press.

15. Olesen J, Friberg L, Olsen TS (1990). Timing and topography of cerebral blood flow, aura and headache during migraine attacks. Ann Neurol, 28(6): 791-798.

16. Tfelt-Hansen PC (2010). History of migraine with aura and spreading depression from 1941 onwards. Cephalalgia, 30(7): 780-792.

17. Sanchez-Del Rio M, Reuter U, Moskowitz MA (2006). New insights into migraine pathophysiology. Curr Opin Neurol, 19(3): 294-298.

18. DiLorenzo C, Grieco GS, Santorelli FM (2012). Migraine headache: a review of the molecular genetics of a common disorder. J Headache Pain, 13(7): 571-780.

19. Rudkjobing LA, Esserlind AL, Olesen J (2012). Future possibilities in migraine genetics. J Headache Pain, 13(7): 505-511.

20. Gepetti P, Rossi E, Chiarugi A, Benemei S. Antidromic vasodilatation and the migraine mechanism. J Headache Pain, 13(2): 103-111.

21. Headache Classification Committee of the International Headache Society (2013). The International Classification of Headache Disorders, 3 [rd] edition (beta version). Cephalalgia,33(9):629-808.

22. Lipton RB, Dodick D, Sadovsky R, Kolodner K, Endicott J, Hettiarachchi J, Harrison W (2003). A self-administered screener for migraine in primary care. Neurology, 61: 375-382.

23. Bendtsen L, Jensen R (2006). Tension-type headache: the most common, but also most neglected, headache disorder. Curr Opin Neurol, 19(3):305-9.

24. Nesbitt AD, Goadsby PJ (2012). Cluster headache. Br Med J (Clinical Research ed), 344: e2407.

25. Lipton RB, Bigal ME, Steiner TJ, Silberstein SD, Olesen J (2004). Classification of primary headaches. Neurology, 63(3): 427-435.

26. Gilmore B, Michael M (2011). Treatment of Acute Migraine Headache. Am Fam Phys, 83(3):271-280.

27. Lewis DW. Pediatric migraine. Neurol Clin, 27(2): 481-501.

28. Schankin CJ, Straube A (2012). Secondary headaches: secondary or still primary? J Headache Pain, 13(4): 263-270, 2012.

29. Tsushima Y, Endo K (2005). MR imaging in the evaluation of chronic or recurrent headache. Radiology, 235 (2): 575-579.

30. Kurth T, Mohamed S, Maillard P (2011). Headache, migraine and structural brain lesions and function: population-based Epidemiology of Vascular Ageing-MRI study. Br Med J, 341: c7357.

31. Scher AI, Gudmundsson LS, Sigurdsson S (2009). Migraine headache in middle age and late-life brain infarcts. JAMA, 301(24): 2563-2570.

32. Nappi RE, Nappi G (2012). Neuroendocrine aspects of migraine in women. Gynecol Endocrinol, 28(suppl 1): 37-41.

33. Rapoport AM (2008). Acute and prophylactic treatments for migraine: present and future. Neurol Sci, 29 (suppl 1): S110-122.

34. Kalra AA, Elliott DE (2007). Acute migraine: Current treatment and emerging therapies. Ther Clin Risk Management, 3(3): 449-459.

35. Chowdhury D (2010). Acute management of migraine. JAPI, 58 (suppl 4): 21-25.

36. Katsarava Z, Obermann M (2013). Medication overuse headache. Headache, 26(3): 276-281.

37. Morren JA, Galvez-Jimenez N (2010). Where is dihydroergotamine mesylate in the changing landscape of migraine therapy? Expert Opin Pharmacother, 11(18): 3085-3093.

38. Bigal ME, Ferrari M, Silberstein SD, Lipton RB, Goadsby PJ (2009). Migraine in the triptan era: lessons from epidemiology, pathophysiology and clinical science. Headache, 48 (suppl 1): S21.

39. Tepper SJ (2012). Serotonin syndrome. Headache, 52(2): 195-197.

40. Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE (2010). The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Socety position paper. Headache, 50(6): 1089-1099.

41. Dodick DW, Lipton RB, Ferrari MD (2004). Prioritizing treatment attributes and their impact on selecting an oral triptan: results from the TRIPSTAR Project. Curr Pain Headache Res, 8(6): 435-442.

42. Lipton RB, Stewart WF, Stone AM, Láinez MJ, Sawyer JP (2000). Stratified care vs. step care strategies for migraine: the Disability in Strategies of Care (DISC) Study: A randomized trial. JAMA, 284(20): 2599-2605.

43. Schürks M, Diener HC, Goadsby P (2008). Update on the prophylaxis of migraine. Curr Treat Options Neurology, 10(1): 20-29.

44. Galletti F, Cupini LM, Corbelli I, Calabresi P, Sarchelli P (2009). Pathophysiological basis of migraine prophylaxis. Prog Neurobiol, 89(2): 176-192.

45. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E (2012). Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults. Neurology, 78(17): 1337-1345.

46. Smitherman TA, Walters AB, Maizels M, Penzien DB (2011). The use of antidepressants for headache prophylaxis. CNS Neurosci Ther, 17(5): 462-469.

47. Gales BJ, Bailey EK, Reed AN, Gales MA (2010). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the prevention of migraines. Ann Pharmacother, 44(2): 360-366.

48. Pittler MH, Ernst E (2010). Feverfew for preventing migraine. Cochrane Database Syst Rev, CD002286.

49. Markley HG (2012). CoEnzyme Q10 and riboflavin: the mitochondrial connection. Headache, 52(suppl 2): 81-87.

50. Kamthan PS. (2004). How to cure Headaches and Facial Neuralgia, Glaucoma, Toothache etc. with Homeopathy. Delhi: B. Jain.

51. Mauskop A (2005). Vagus nerve stimulation relieves chronic migraine and cluster headaches. Cephalalgia, 25(2): 82-86.

52. Magis D, Sava S, Sasso d’Elia T, Baschi R, Schoenen J (2013). Safety and patient satisfaction of transcutaneous Supraorbital Neurostimulation (tSNS) with the Cefaly device in headache treatment: a survey of 2,313 headache sufferers in the general population. J Headache Pain, 14: 95.

53. Lambru G, Matharu MS (2012). Occipital nerve stimulation in primary headache syndromes. Ther Adv Neurol Disord, 5(1): 57-67.
About Author:

Miles E. Drake
Ph.D., M.D

A.B.- Harvard University
M.D.- Duke University School of Medicine

Professor emeritus (1982 to 2007) -Ohio State University College of Medicine and Public Health
Lecturer (2007-2013) - AGU School of Medicine
I can recall a young female patient who came to my office complaining of major headaches, occurring at any time of the day with no specific triggers. During the history taking process I tried to gather as much information as possible to zero in on a diagnosis. I was convinced it was a tension headache as opposed to migraines; although she had already self diagnosed herself with migraines. She did not fit the criteria for migraines with or without an aura, so I was more convinced it was tension headaches. I decided to monitor her after treating her for tension headaches and while she was in the waiting room, instinct told me to send her for a CT scan. Her CT scan revealed a space occupying lesion which eventually turned out to be a brain tumour. As the saying goes...never take things for granted and always be thorough.

Thanks for starting such helpful thread. I would like to participate in it

Possibly Related Threads...
Last Post
Replies: 0
Views: 1,519
10-22-2015, 03:22 AM
Last Posthectorduvan89

Users browsing this thread:
1 Guest(s)

Migraine: Diagnosis and Classification of Headache51