Migraine

Classification and Clinical Features of Migraine

Migraine is defined as an idiopathic recurring headache disorder with attacks that last 4–72 hours. Typical characteristics are unilateral location, pulsating quality, moderate or severe intensity, and aggravation by routine physical activity. There is also usually nausea, photophobia and phonophobia.

Migraine can be a disabling condition for the sufferer. Most migraine headaches are successfully managed by the patient and their general practitioner, but a small number fail to respond or become ‘fixed’, and sufferers may present for treatment at EDs. As most patients (up to 80% in some studies) have tried oral medications prior to presenting, parenterally administered agents.

In some patients migraine is preceded by an ‘aura’ of neurological symptoms localizable to the cerebral cortex or brain stem, such as visual disturbance, paraesthesia, diplopia or limb weakness. These develop gradually over 5–20 minutes and last less than 60 minutes. Headache Opens in new window, nausea and/or photophobia usually follow after an interval of less than an hour.

Several variant forms of migraine have been defined, including ophthalmoplegic, abdominal, hemiplegic and retinal migraine, but all are uncommon. In ophthalmoplegic migraine the headache is associated with paralysis of one or more of one or more of the nerves supplying the ocular muscles. Horner’s syndrome may also occur.

Abdominal migraine manifests as recurrent episodes of abdominal pain for which no other cause is found. Retinal migraine, which is fortunately very rare, involves recurrent attacks of reticnal ischaemia which may lead to bilateral optic atrophy. Hemiplegic migraine is a stroke mimic.

Pathophysiology

The pathophysiology of migraine is complex and not completely understood. It is probably the result of interaction between the brain and the cranial circulation in susceptible individuals.

The phenomenon of ‘cortical spreading depression’ is probably the event underlying the occurrence of an aura in migraine. This is a short-lasting depolarization wave that moves across the cerebral cortex. A brief phase of excitation is followed by prolonged depression of nerve cells. At the same time there is failure of brain ion homoeostasis, an efflux of excitatory amino acids from nerve cells, and increased energy metabolism. This phenomenon appears to be dependent on the activation of an N- methyl-D-aspartate receptor, which is subtype of the glutamate receptor.

The headache pain of migraine seems to result from the activation of the trigemino-vascular system. The trigeminal nerve transmits headache pain from both the dura and the pia mater. The triggers for the development of migraine headache are probably chemical and are thought to originate in the brain, the blood vessel walls and the blood itself.

These triggers stimulate trigeminovascular axons, causing pain and the release of vasoactive neuropeptides, including calcium G-related peptide (CGRP) from perivascular axons. These neropeptides act on mast cells, endothelial cells and platelets, resulting in increased extracellular levels of arachidonate metabolites, amines, peptides and ions. These mediators and the resultant tissue injury lead to a prolongation of pain and hyperalgesia.

Serotonin has also been specifically implicated in migraine. By activation of afferents, it causes a retrograde release of substance P. This in turn increases capillary permeability and oedema.

Treatment

The complexity of the mechanisms involved in the genesis of migraine suggests that there are a number of ways to interrupt the process to provide effective relief from symptoms.

A wide variety of pharmacological agents and combinations of agents have been tried for the treatment of migraine, with varying results. Interpreting the evidence is challenging, as the majority of the studies have small sample sizes, compare different agents or combinations of agents, are conducted in settings other than EDs, and the outcome measure(s) tested varies widely.

Because the ED migraine population appears to be different from the general outpatient population, the data presented here are based on studies in emergency departments (EDs).

At present the most effective agents seem to be the phenothiazines (chlorpromazine, prochlorperazine, droperidol and possibly haloperidol) and the tripans, each of which has achieved > 70% efficacy in a number of studies. Note that tripans are contraindicated in patients with a history of ischaemic heart disease, uncontrolled hypertension or with the concomitant use of ergot preparations.

Pethidine is not indicated for the treatment of migraine. Its reported effectiveness is only 56%, it has a high rate of rebound headache and it carries a risk of dependence. In two small RCTs haloperidol administered as 5mg in 500 mL normal saline was reported to give significant pain relief in more than 80% of patients.

Lignocaine (lidocaine) has been shown to be no more effective than placebo. The data on dihydroergotamine are difficult to interpret because it is often used in combination with other agents, e.g. metoclopramide; however, it has also been shown to be less effective than chlorpromazine and sumatriptan in acute treatment, and to have a high rate of unpleasant side effects. There are insufficient data to recommend this as standard therapy.

    Adapted from: Textbook of Adult Emergency Medicine E-Book. Authored By Peter Cameron, George Jelinek, Anne-Maree Kelly, Lindsay Murray, Anthony F. T. Brown. References as cited include:
  1. Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Acute pain management; scientific evidence, 2nd edn. Canberra: National Health and Medical Council (Australia) 2005.
  2. Friedman BW, Greenwald P, Bania TC, et al. Randomized trial of IV dexamethasone for acute migraine in the emergency department. Neurology 2007 (Epub ahead of print).
  3. Kelly AM. Specific pain syndromes: Headache. In: Mace S, Ducharme J, Murphy M, eds. Pain management and procedural sedation in the emergency department. New York: McGraw-Hill, 2006.
  4. Kelly AM, Kerr D, Clooney M. Impact of oral dexamethasone versus placebo after ED treatment of migraine with phenothiazines on the rate of recurrent headache: a randomized controlled trial. Emergency Medicine Journal 2008; 25:26–29.