Migraine headaches in a nutshell

According to the International Headache Society, a migraine is a headache that lasts for 4–72 hours and presents with at least two of the following symptoms: unilateral localisation, moderate to severe pain intensity, aggravation by movement, and a pulsating feeling. The headache is also usually accompanied by nausea, vomiting, photoand phonophobia.1 Migraine headaches are typically classified into two major subtypes, namely migraine with an aura, and a migraine headache without an aura.2 Migraine is considered to be chronic when it occurs for a minimum duration of four (4) hours per day, and lasts for more than 15 days per month, within a three-month period.3 Chronic migraine is frequently associated with the so-called medicationoveruse-headache.4


Introduction
According to the International Headache Society, a migraine is a headache that lasts for 4-72 hours and presents with at least two of the following symptoms: unilateral localisation, moderate to severe pain intensity, aggravation by movement, and a pulsating feeling.The headache is also usually accompanied by nausea, vomiting, photo-and phonophobia. 1 Migraine headaches are typically classified into two major subtypes, namely migraine with an aura, and a migraine headache without an aura. 2 Migraine is considered to be chronic when it occurs for a minimum duration of four (4) hours per day, and lasts for more than 15 days per month, within a three-month period. 3Chronic migraine is frequently associated with the so-called medicationoveruse-headache. 4 A migraine headache is generally preceded by a premonitory phase that lasts for hours before the headache begins. 1 This phase is characterised by fatigue, mood changes and gastrointestinal problems, which could persist throughout the entire migraine attack. 1 One in five 'migraineurs' (i.e.people who suffer from migraine) also experience an aura, which consists of visual, sensory or motor disturbances. 1The aura phase is followed by actual headache and this, in turn, is followed by a recovery phase, or postdrome (also referred to as a 'migraine-hangover'), with fatigue and continued sensory disturbances.The page number in the footer is not for bibliographic referencing www.tandfonline.com/oemd13 in the central and peripheral neurons, that has been implicated in the transmission of pain signals and is released during severe migraine attacks. 8

Classification
Migraine is usually classified as having two major subtypes, namely migraine with an aura, and migraine without an aura.Additional subtype classifications are depicted in Figure 1.

Diagnosis
The diagnosis is made, based on the clinical presentation or symptoms of the patient, and by excluding other causes of frequent headaches. 9In many cases the pain experienced during migraine attacks, occurs unilaterally. 10The pain is described as severe and is accompanied by nausea and/or vomiting, hypersensitivity to light, sound and odour. 7ronic migraine diagnosis relies on the International Classification of Headache Disorders (ICHD-3) beta criteria, because there are no biological markers for chronic migraine.

Pharmacological management
From a pharmacotherapeutic perspective, migraine management may be divided into prophylactic measures, and the treatment of acute attacks, as described in the following section.

Migraine prevention
Migraine attacks can range in intensity from moderate to severe, and may be preceded by other symptoms. 8The migraines can change from being episodic to being chronic.Although episodic migraine can remain unchanged for years, there is also the likelihood that it could remit or develop into a situation whereby it may be classified as chronic, with an increasing severity and frequency of headaches per month. 8When the headaches do become chronic, it would be highly advisable to look at the migraineur in question and individualise preventative migraine therapy. 8These drugs will, on average, reduce migraine frequency by 50% in about 40-45% of patients; however, compliance and adherence are poor because of their many adverse effects.Drug classes for migraine prevention are described below.

β-blockers
The following beta-blockers have proven efficacy in this setting: atenolol, metoprolol, nadolol, propranolol and timolol. 2 Use of these drugs should be carefully monitored in patients who exhibit undesirable adverse effects and switched to a different class, such as the anti-epileptic agents (e.g.valproic acid). 2

Anti-epileptic agents
Several anti-epileptics have shown increasing potential in migraine prevention.Treatment options include carbamazepine, valproate, gabapentin, topiramate and lamotrigine. 2In this class, topiramate is one of the most effective therapy options to consider in patients with chronic migraine. 2

Serotonin-receptor antagonists
Methysergide is a 5-HT 2 receptor antagonist and 5-HT 1B/D receptor agonist, and pizotifen, a 5-HT 2 receptor antagonist 15 .Both drugs provide adequate and effective prophylaxis against migraines. 15urrently, pizotifen is registered for use in South Africa but mainly considered for use in patients that are refractory to other prophylactic drugs, due to the high cardiac adverse effect profile.The use of pizotifen should not be longer than six months. 15

Other agents
Flunarizine is a calcium channel blocker that also has antihistaminergic properties.It is used for migraine prophylaxis and in some instances, as a first line drug in children with hemiplegic migraines. 16Other calcium-channel blockers include verapamil. 2Angiotensin II-receptor antagonists (e.g.candesartan), and certain antidepressants (e.g.amitriptyline and venlafaxine), are other potential options. 2

Botulinum toxin A
Onabotulinum toxin A is classified as a neurotoxin, which is primarily a product of the anaerobic bacterium, Clostridium botulinum.The toxin appears to exert its mechanism of action by inhibiting the release of nociceptive mediators involved in the pathogenesis of migraine. 4These include substance P, CGRP and glutamate; it inhibits these nociceptive mediators from the peripheral nerve terminals of primary afferents. 4In the two randomised clinical trials that the drug underwent, it was evident from the data collected that onabotulinum toxin A is a safe, well-tolerated, and an effective prophylactic treatment in patients suffering from chronic migraine.

Managing acute attacks
Acute migraine attacks should be treated early, when the pain is still mild and current guidelines recommend non-steroidal antiinflammatory drugs (NSAIDs), aspirin and paracetamol for the treatment of acute mild to moderate migraine attacks. 9Many of the drugs used for the treatment of acute migraine attacks are also used for treating chronic migraine. 9got alkaloids, such as ergotamine, are 5-HT-receptor agonists and bind to α-adrenoceptors and dopamine receptors. 4Their use has been reduced since the arrival and introduction of the triptans. 4Their use has also been declining due to their unwanted side-effects, inconvenience and a high likelihood for causing medication-overuse headaches. 2matriptan was specifically formulated for the treatment of acute migraine attacks.It has a high specificity for the 5-HT 1B and 5-HT 1D serotonin receptors. 2This mechanism of action produces cerebral vasoconstriction, secondary to their inhibition of calcitonin gene-related peptide (CGRP) and inflammatory peptide release. 2 The triptans are most effective when they are taken when the pain is mild to moderate. 8There are a few more triptans that have been introduced for use in South Africa, including zolmitriptan, naratriptan, rizatriptan and elitriptan.The concomitant use of other agents that increase serotonin levels, such as the SSRIs and the serotonin-noradrenaline reuptake inhibitors (SNRIs), should be avoided due to the danger of developing serotonin syndrome. 11The triptans should also be avoided in patients with a history of ischemic heart disease, cerebrovascular disease and uncontrolled hypertension. 12novel, highly-selective 5-HT 1F -receptor agonist, with a seemingly good cardiovascular safety profile, namely lasmiditan, is currently in clinical development.Two CGRP antagonists have also shown promise during clinical development, namely olcegepant and telcagepant. 13The latter has, however, been discontinued due to safety concerns. 14

Conclusion
Migraine headaches are commonly encountered in the clinical practice setting.Patients suffering from migraine must endure an often-debilitating neurological disorder, with frequent attacks of severe headache that require acute, abortive treatment.The recurrence of these episodes may also be markedly decreased using effective, preventive measures, including the use of prophylactic medication.The clinician may play a vital role in the effective management of migraine through the promotion of a better understanding of the correct and effective use of migraine treatment options, as well as the reduction and management of associated risk factors and behaviours.

Migraine with aura Typical aura Figure 1: Subtype classifications of migraine 10
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Table I :
10ternational Classification of Headache Disorders diagnostic criteria for migraine10 3

Table II :
Classes and examples of drugs that are used in the prevention of migraine headaches in adults, in South Africa 2 2

Table III :
10AIDS used for acute migraine treatment in adults10

Table IV :
10iptans used for acute migraine treatment in adults10