Introduction: Migraine is the commonest neurological disorder and the most frequent condition for referral to neurological departments. It is a leading cause of disability as ranked by the World Health Organisation and can effect individuals of all ages from childhood to old age. The prevalence of migraine is 10-12% of the population, is three times more common in women, and the peak prevalence is between the ages of 30-50 years. Migraine prevalence declines in post-menopausal women and the natural history is that migraine goes into remission in older age. However there are exceptions and individual can continue to suffer from migraine into old age.
Written by Dr Edward O’Sullivan, Director, Migraine Clinic, Cork University Hospital
Diagnosis
The International Headache Society has standardised the clinical diagnostic criteria for migraine and these guidelines are universally adopted by physicians worldwide. The majority of migraneurs will diagnostically fulfil one of the list in fig.1
1.Episodic Migraine Without Aura
2.Episodic Migraine With Aura
3.Chronic Migraine
4.Vestibular Migraine
Fig.1
The cardinal features of a migraine attack are recurrent bouts of severe headaches, which can be unilateral or bilateral, is throbbing and pounding in character and exacerbated by movement. The headaches are accompanied by nausea which can lead to vomiting, photophobia and phonophobia. 20-30% of patient may experience aura symptoms which can either precede or coincide with the headache. The commonest aura symptoms are visual lasting 5-60 minutes and consists of flashing light, zig-zag lines, and an expanding scintillitating scotoma. Other aura symptoms are sensory paraesthesia, motor weakness and dysphasia.
In 10% of migraine patients the condition becomes a progressive disorder and they insidiously develop Chronic Migraine as defined in Fig.2.
Chronic Migraine: 1.3
A. Headache (TTH-like and /or Migraine-like on >15 d/mo for > 3 month and fulfilling criteria B and C.
B. In a patient who has had > 5 attacks of fulfilling criteria
B-D
For 1.1 Migraine Without Aura and /or criteria B and C for 1.2 Migraine With Aura
C. On > 8 d/month for > 3 month fulfilling any of the following:
1.Criteria C and D for Migraine Without Aura
2.Criteria B and C for Migraine With Aura
3.Believed by the patient to be migraine at onset and relieved by a triptan or ergot derivative
D. Not better accounted for by another ICHD-3 diagnosis
Fig.2
3% of Episodic Migraine patients convert to Chronic Migraine on an annual basis. Risk factors for progression include: increasing age, female, medication-overuse (acute therapies), ineffective acute therapies, obesity and co-morbid anxiety / depressive disorders.
Migraine Disability
A number of measurement tools are used to evaluate the disability and quality of patients who suffer from migraine. The MIDAS (migraine disability assessment score) and the HIT (headache impact test) were developed in the triptan era and in more recent times the Migraine specific quality of life questionnaire was pioneered to evaluate patients who have Chronic Migraine. Individuals, during attacks are frequently unable to carry out routine daily activities and typically have to lie down in a quiet dark room, resorting to comfort measures such as applying a cold compress or tying a scarf around their head. Time lost from work, lost productivity, cancelled social engagements, and family life are all greatly impacted with consequences for the individual and the wider family.
Pathophysiology of Migraine
Migraine is a recurrent neurological disorder and the trigemino-vascular theory gives a clear understanding of the mechanisms for pain transmission. The ophthalmic division of the trigeminal nerve and the upper cervical nerves are the pain sensitive pathway and these nerves innervate the meninges, dura mater, large intracranial arteries and the dural venous sinuses. During a migraine attack, on activation of the trigemino-vascular system, either spontaneously or by a trigger factor, neuropeptides are released from the peripheral end of these nerves. These neuropeptides include C.G.R.P. (calcitonin gene related peptide), neurokinin and substance P. These peptides cause a neurogenic inflammatory reaction in the meninges and large intracranial arteries activating first order neurons in the trigeminal nerve and the transmission of a painful afferent signal to the trigeminal nucleus caudalis and upper cervical nuclei (trigemino-cervical complex). 2nd order neurons relay messages to the thalamus and 3rd order neurons further relay signals to the higher centres in the cerebral cortex where pain is perceived.
Trigger Factors and Migraine
The identification of migraine trigger factors is a cornerstone in the history taking in patients who suffer from migraine. Notwithstanding their importance, triggers are only identifiable in approximately 40% of patients. The common trigger factors are listed in fig. 3.
Trigger Factors
- Stress and Anxiety, overtiredness and lack of sleep
2. Diet / Food additives: MSG, aspartate, dairy products, processed foods
3. Alcohol
4. Caffeine
5.MISSED MEALS
6.Menstrual cycle. Usually just prior
7.Bright lights and loud noises
8.Changing weather conditions
9.Exercise
10.Combined Oral Contraceptives
11.Pregnancy
Fig.3
Diet and Migraine
1.Caffeine: Caffeine has a similar structure to adenosine and is an antagonist at adenosine A1 and A2 receptors in the brain. Caffeine is rapidly absorbed and easily crosses the blood-brain barrier. It is contained in many drinks most notably coffee, but also cocoa, soft drinks, and energy drinks. Caffeine is also contained in analgesics such as excedrin, solpadeine and anadin extra. In low dose caffeine has analgesics properties and is often used to enhance the efficacy of simple analgesics, paracetamol and aspirin providing additional and more rapid relief from headache and acute migraine attacks. However, increased intake of caffeine leads to tolerance and habituation and patients are at risk of dependence leading to increased headache frequency and progression to the development of Chronic Migraine. Withdrawal can result in rebound headache and the continued risk of escalating caffeine consumption. The safe daily intake of caffeine should be limited to 200mg (- 3 cups of coffee per day)
2.Food Additives: In a number of studies, 12%-60% of migraineurs have reported dietary foods as a trigger with many identifying more than 1 dietary trigger. The common dietary triggers are foods containing MSG (monosodiumglutamate) e.g curries, pizzas processed meat, aspartate e.g chocolate, and tyramine e.g. cheese. There is no scientific evidence demonstrating causation between dietary triggers and migraine. The link is based on observations facilitated by the use of headache diaries. In addition multifactorial factors involving multiple triggers including diet, overtiredness, lack of sleep, stress and the menstrual cycle are frequently reported by individuals. General advice is to avoid incriminating dietary triggers with the goal of reducing the frequency of migraine.
Alcohol and Migraine: Alcohol consumption is frequently reported as a trigger for migraine and other headache types and up to 1/3rd of migraine patients have identified alcohol as a trigger. Red wine is most commonly identified, but white wine and other alcohol beverages can also cause headache. The causative ingredients is controversial but biogenic amines, sulphites, flavonoid phenols, and 5hydroxytyramine mechanisms lead to vasodilating processing and activation of the trigeminovascular system. Alcohol itself is a potent vasodilator and is known to release C.G.R.P. (calcitonin gene related peptide) a neuropeptide which is intrinsically involved in the pathogenesis of migraine. In migraine patients the headache onset is often acute and begins within 3 hours of intake and can occur after a single drink. As a result many migraneurs are fearful of alcohol, reduce their intake and consume with caution.
Delayed onset headache usually begins the following day when the alcohol level has returned to near zero, hence the term ‘’hangover’’ headache and is probably due to different mechanisms. “Hangover” headache is common, occurs in both migraine and non-migraine individuals and is more likely to occur with alcohol excess.
Sugar and Migraine
The relationship between dieting, food intake, meal times, fasting, missed meals, exercise and migraine is well established. Low blood sugar levels and the sympathetic drivers to maintain normal blood sugars are thought to trigger migraine. The control of appetite is a function of the hypothalmus and disruption of these homeostatic mechanisms in susceptible individuals will trigger migraine. In communities where people fast as in the month of Ramadan, studies have demonstrated an increase in the frequency and severity of migraine attacks. Dehydration and electrolyte imbalance also play a part.
Migraine patients commonly report fasting, either intentionally or by a missed meal, as a trigger for their migraines. Recent studies have reaffirmed a genetic predisposition between migraine attacks and low blood sugar. Altered glucose transport into the brain is associated with hemiplegic migraine and migraine with aura. The hypothalmus is activated early during migraine attacks, the premonitory phase, when symptoms such as tiredness, fatigue, yawning, dizziness and certain food cravings are present. This activation is postulated to be an adaptive behavioural response to hypoglycaemia or an energy compromised brain. There follows a latent period of up to a number of hours before the onset of headache which develops on activation of the trigeminovascular system.
Another hypothesis in migraine is insulin resistance both peripherally and in the brain. This leads to downregulation of insulin receptors in astrocytes and neurons resulting in reduction of glucose uptake and glycogen synthesis particularly at times of high metabolic demand. These leads to a cascade of changes in neuronal metabolism in hippocampus, amygdala and cerebral cortex.
Management of Migraine
It’s never been a better era to be a migraine sufferer. Scientific advancement has lead to the discovery of migraine specific therapeutic medications for both the treatment of acute attacks and the prevention of future attacks. The triptans, C.G.R.P. monoclonal antibodies, and small molecule gepants are now part of our armamentarium and have transformed our ability to manage migraine. The landscape continues to change with further treatments in late stage clinical development, including the ditans, 5HT1F antagonists for acute attacks and PACAP (pituitary adenylate cyclase activating peptide) inhibitors for prevention.
Conclusions
Migraine is a recurrent headache disorder with most experiencing episodic attacks whilst for others it becomes a progressive disorder leading to chronic migraine. Headache diaries, in clinical practice, have always been a cornerstone in the management of migraine, particularly now that we have new and better medications. The identification of trigger factors, many of which are dietary, is facilitated by keeping accurate up to date diaries. The self-awareness generated and the vigilance applied by this exercise reduces the overall frequency of migraine and the avoidance of certain attacks.
