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Mon 1 Jan 2007 11:48 AM

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Mind over matter

One third of patients in the waiting room of a primary care physician are sufferers. HME examines the roots of migraine management

Migraine without aura, previously known as common migraine, is a chronic neurovascular disorder that affects between 5-25% of women and 2-10% of men worldwide. It is a markedly disabling condition that places a significant burden on sufferers in terms of pain, direct and indirect costs of care and impaired quality of life. Many patients are unable to work, or their work productivity is reduced during and between attacks. The impact of migraine is evident not only in the workplace, but also on family life, relationships, and overall well-being.

Migraine attacks may start at any age. World Health Organisation figures demonstrate that 16% of school children in Egypt suffer from migraine. While the incidence of migraine is similar for both sexes during childhood, its incidence increases in females after puberty. The prevalence of migraine among male patients peaks around age 35, while prevalence among female patients tends to increase during the first few decades of life, peaking around 40, and then declining over the next few decades. An estimated 70% of all migraine sufferers are women, and this significantly greater incidence, studies show, holds throughout the world and in every culture.

While an estimated two thirds of migraine sufferers are managed in a primary care, diagnosis and treatment remain suboptimal. It is thought that one third of migraine sufferers go undetected. Affected patients will seek medical care, but not specifically for symptoms of migraine. Conversely, headache is one of the most common symptoms reported in primary care, indicating that routine screening for migraine may help clinicians identify patients in need of further evaluation.

Early recognition and management of migraine can translate into a reduced chance of illness (chronic daily headache can be a consequence of poor migraine management), reduced patient dependency on medications and fewer practice and emergency department visits; overall, prompt recognition improves patient outcome at every level.


Understanding of the pathophysiology of migraine continues to evolve. Theories on the pathogenesis of migraine include the vascular theory; the cortical spreading depression theory; the neurovascular hypothesis; the serotonergic abnormalities hypothesis and the integrated hypothesis. The onset of migraine was originally explained using the vascular hypothesis. This theory suggests that the aura of migraine is caused by vasoconstriction and reduction in cerebral blood flow, while the migraine itself is the result of a compensatory vasodilation of these same intracerebral arteries. Although it has been shown that during the aura of migraine there is decreased cerebral blood flow, other studies do not support this hypothesis. Currently it is believed that migraine involves dysfunction of brainstem pathways that normally affect input of sensory information. Positron emission tomography studies have shown that there is activation of the brainstem at the onset of migraine. It has also been shown that specific serotonin (5-HT) receptor subtypes (5-HT and 5-HT ) may be involved in the pathophysiology of migraine. These receptors are also the targets of medications used in the treatment of acute migraine.

Genetic links

Many positive association studies have documented that migraine runs in families, with a strong familial influence demonstrated in twin studies. Mutations in the calcium-channel gene CACNA1A, located on chromosome 19, have been found responsible for familial hemiplegic migraine (FHM) in some families, and a link to chromosone 19 also appears to occur in some families with more commonly occurring migraine. More recently, De Fusco and colleagues identified a point mutation in the ATP1A2 gene associated with familial hemiplegic migraine type 2, while Ambrosini and colleagues linked the same mutation to basilar migraine (BM).

It is clear that the genetic background of migraine is complex. Migraine is a polygenic, multifactorial condition, with headache attacks varying in frequency, duration, and symptomatology both between sufferers, and between attacks in the individual sufferer. As a result, there are difficulties in evaluating sufferers and few positive association studies have been replicated. Nevertheless, genetic studies continue to provide important information about the molecular basis of migraine.


Migraine without aura is characterised by episodes of throbbing, unilateral head pain. Attacks are associated with nausea, vomiting, or sensitivity to light, sound or movement. When untreated, symptoms typically last between four and 72 hours, although the duration may be less in children. Differentiating between migraine without aura and episodic tension-type headache may be difficult. Tension type headache is the most common form of primary headache and is characterised by the lack of associated features. Any severe and recurrent headache is most likely to be a form of migraine and is also likely to be responsive to antimigraine therapy.

It has widely accepted that migraine triggering factors can prompt an attack in sufferers. Migraine precipitants vary between sufferers, although certain foods, hormonal fluctuations and stress are common targets. Approximately half of female migraine sufferers report episodes associated with their menstrual cycle and for some women, the first three months of pregnancy can exacerbate attacks. Women whose migraines are affected by pregnancy or menstruation are also likely to have more severe migraines if they take oral contraceptives.

Migraine sufferers have a higher incidence of comorbidities than nonmigraineurs, with a higher risk of coexisting affective or anxiety disorders, stroke, epilepsy, or sleep disorders. Additional conditions can include asthma and allergies, infection with H. pylori, fibromyalgia, systemic lupus erythematosus, Raynaud's syndrome and mitral valve prolapse.

Diagnosing migraine

The goals of diagnosis are to exclude serious underlying disease as a cause for migraine (secondary headache) and to diagnose primary headache (not caused, or a symptom of, another disease or condition).

The diagnostic criteria established by the International Headache Society (see ‘At a glance: diagnostic criteria for migraine without aura') are widely followed. In summary, a diagnosis can usually be made if the patient reports at least unilateral headaches, each lasting 4 to 72 hours, accompanied by photophobia, phonophobia, nausea, vomiting, and other symptoms, and if other forms of common persistent headache are ruled out.

Migraine is substantially underdiagnosed, so a complaint of headache should prompt further questioning. Clinicians should begin with a comprehensive patient history, including neurologic family history, and physical exam. Enquire about any conditions that might be associated with headache, including chronic or recent illnesses and treatments; injuries (particularly head or back); dietary changes; medications; history of drug, alcohol, or caffeine abuse; and stress, depression or anxiety. A standard screening method can aid in identifying patients with unreported migraine symptoms. Relevant enquires may include:

• Duration and frequency of headaches

• Recent changes in how the headaches feel

• Location of pain

• Type of pain. Is it throbbing or is there a steady pressure?

• Intensity of the headache (on a scale in which 1=mild and 5=incapacitating)

• Associated symptoms, such as visual disturbances or nausea and vomiting

• Headache behaviours

• What appears to trigger the headache? (Food, fatigue, menstrual cycle etc.)

• What seems to relieve it?

• What non-drug treatments have been tried?

Clinicians may also find patient headache worksheets useful (See ‘At a glance: further resources.). Many headache centers, such as that at the US-based Cambridge Health Alliance, use these comprehensive questionnaires to record information about the type of pain, location, triggers, and accompanying symptoms a patient reports. Such tools can aid clinicians in determining the impact the pain has on the patient's life, and enable the patient to better communicate this information. Worksheets can also be used to effectively track the patient's migraine history and the effectiveness of therapy over time, often in combination with a personal "headache diary". Diaries may also be effective in helping patients identify and eliminate trigger factors that influence their headaches. During episodes, patients should try, as a minimum, to capture the date, duration and intensity of the attack, any preceding symptoms, suspected triggers and any medication administered; including relief, if any.

The American Headache Society has established a simple red flag system to prompt screening for secondary headaches during migraine diagnosis. The system can be easily remembered by the mnemonic SNOOP:

• Systemic symptoms; such as fever or weight loss or

• Secondary risk factor; such as HIV or systemic cancer

• Neurologic symptoms: or abnormal signs such as confusion, impaired alertness, papilledema, asymmetry, motor weakness, nuchal rigidity, visual disturbance other than aura, dysphasia

• Onset: sudden, abrupt, split-second, seconds to minutes, rapid onset of headache

• Older: New headache onset in an older patient or a progressively worsening headache in a middle-aged patient (>50 years of age)

• Progression pattern: Previous headache history-A major change in attack frequency, severity, or clinical features; a first headache or different headache unlike any experienced before.

The presence of any of these symptoms should prompt further investigation. While diagnostic testing is useful when neurologic and systemic findings are present, to rule out secondary or ominous headache; it cannot diagnose primary headache. When exam results are normal, headaches are recurrent and their pattern stable, and pain is severe and temporarily disabling, the likely diagnosis is migraine without aura.


Migraine sufferers differ in their management needs, largely due to the variation in severity of symptoms and their impact on the sufferer. Treatment should be tailored to the individual patient, and therapeutic decisions should be influenced by attack frequency, attack variability, migraine-induced disability, coexisting conditions and overall treatment outcomes.

Pharmacological management typically can be divided into three categories: acute, preemptive or preventive. Acute treatment is initiated during an attack to relieve pain and disability. Preemptive treatment is used when a known headache trigger exists, and preventive treatment is maintained to reduce attack frequency, severity, and duration.

The US Headache Consortium Guidelines recommend stratified care, and include agents for acute treatment (such as NSAIDS, opiates, and combination analgesics) and migraine-specific treatments (such as ergotamine, dihydroergotamine, and the triptans). The Migraine Disability Assessment (MIDAS) scale can be used to classify patients. The scale is designed to identify sufferers most severely affected by their migraine and, therefore, most in need of care (see ‘At a glance: the MIDAS questionnaire).

Effective preventive medications range from anti-convulsives, specifically topiramate and valproic acid, to off-label agents including selective serotonin reuptake inhibitors (SSRIs), and beta-blockers such as propanolol and verapamil. Therapy should be initiated at the lowest effective dose, and increased slowly until clinical benefits are achieved without adverse effects. Acute medications range from analgesics for mild to moderate migraine, to triptans, in spray or orally disintegrating form, for moderate to severe migraine. Triptan injections may also be prescribed. For preemptive treatments, triptans are first line therapy, unless contraindicated. Full prescribing recommendations can be found on the American Headache Society website.

Future therapies are also promising. Recently approved treatments, levetiracetam and zonisamide, can be used effectively off-label with careful explanations. Another promising treatment is botulinum toxin; injections into forehead and brow muscles have been reported to improve migraine symptoms.

For the majority of patients, migraine symptoms can be managed within primary care. However, if symptoms are unchanging or worsening, comorbidities are present requiring polypharmacy, and the patient is considered unsuitable for outpatient management, referral should be made to a neurologist.


Time spent educating patients on migraine can result in reduced anxiety, and increased understanding of treatment goals and improved compliance with the treatment regime. Physicians should offer a clear, concise explanation for the diagnosis, ensure questions are answered simply and fully, and invite patient participation in treatment decisions. A structured treatment plan with clear follow-up can aid in this.

Behavioural therapies can provide an important adjunct to pharmacological management of migraine. Avoiding triggers is an important factor in reducing migraine attacks, and patients will benefit from behavioural strategies of improved diet, exercise, and lifestyle and stress management. Physicians should educate patients about non-drug therapies such as anti-migraine nutrition, exercise, relaxation, biofeedback, yoga, and meditation. Alternative treatments such as acupuncture, physical therapy, and massage may also prove beneficial to migraine sufferers.

At a glance: diagnostic criteria for migraine without aura*

A minimum of five attacks fulfilling the following criteria:

• Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)

• Headache has at least two of the following characteristics:

> Unilateral location

> Pulsating quality

> Moderate or severe pain intensity

> Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs)

• During headache at least one of the following:

> Nausea and/or vomiting

> Photophobia and phonophobia

• Not attributed to another disorder

*As specified by the International Headache Society

At a glance: the MIDAS questionnaire*


Please answer the following questions about all the headaches you have had over the last three months. Write your answer next to each question. Write zero if you did not do the activity in the last three months.

1. On how many days in the last three months did you miss work or school because of your headaches?

2. How many days in the last three months was your productivity at work or school reduced by half or more because of your headaches? (Do not include days you counted in question 1 where you missed work or school.)

3. On how many days in the last three months did you not do household work because of your headaches?

4. How many days in the last three months was your productivity in household work reduced by half or more because of your headaches? (Do not include days you counted in question 3 where you did not do household work.)

5. On how many days in the last three months did you miss family, social, or leisure activities because of your headaches?

A. On how many days in the last three months did you have a headache? (If a headache lasted more than one day, count each day.)

B. On a scale of 0–10, on average how painful were these headaches (where 0=no pain at all, and 10=pain as bad as it can be)?

Grade Definition Score

• Minimal or infrequent disability 0–5

• Mild or infrequent disability 6–10

• Moderate disability 11–20

• Severe disability 21+

*Stewart et al (Cephalagia,1999;19:107-14)

At a glance: further resources

• The International Headache Society; for diagnostic criteria:

• The National Headache Foundation; for diagnostic tools, and patient education resources:

• US Headache Consortium Guidelines: evidence-based treatment for migraine in primary care:

• Migraine Disability Information Centre; for downloadable MIDAS forms and patient education:

“The goals of diagnosis are to exclude serious underlying disease and to diagnose primary headache.”
“Time spent educating patients on migraine can result in reduced anxiety,increased understanding of treatment goals, and improved compliance.”

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