Yan Wenming, Department of Radiotherapy, Affiliated Hospital of Inner Mongolia Medical University
Reviewed by Liu Zhibing and Sun Lihua Yan Wenming (reviewer)
Chinese Journal of Practical Medicine, 2007, Vol. 1, No. 1: 36-
Migraine is a common and frequent clinical disease characterized by severe headache, either left or right, with repeated attacks and throbbing pain, usually lasting 4 to 72h. It may be accompanied by nausea and vomiting. Typical migraine patients have prodromal symptoms and triggering factors such as mood swings, lack of sleep, and alcohol consumption. Light, sound or activity can aggravate the headache, while rest in a quiet environment can relieve the headache.
Aura refers to a completely reversible focal neurological symptom that occurs before or along with the headache and manifests as visual, sensory, proverbial, or motor deficits or irritation symptoms. Most auras are visual symptoms, often binocularly isotropic, such as blurred vision, dark spots, bright spots and bright lines, or distorted vision. Sensory symptoms are mostly distributed in the face-hand region. Aura symptoms usually develop gradually within 5-20 min and last no more than 60 min. different aura can appear one after another [1].
1 Classification and diagnosis of migraine
1.1 Classification of migraine [2, 3]: The second edition of the International Classification of Headache Disorders (ICHD-2) of the IHS in 2004 classifies migraine as primary headache, including six subtypes (see Table 1), with migraine without aura and migraine with aura being common.
Table 1 International ICHD-II migraine typology
1.1 Migraine without aura
1.2 Migraine with aura
1.2.1 Migrainous headache with typical aura
1.2.2 Non-migraine headache with typical aura
1.2.3 Typical aura without headache
1.2.4 Familial hemiplegic migraine
1.2.5 Sporadic hemiplegic migraine
1.2.6 Basal migraine
1.3 Periodic syndromes in children that are often precursors to migraine
1.3.1 Periodic vomiting
1.3.2 Abdominal migraine
1.3.3 Benign episodic vertigo in children
1.4 Retinal migraine
1.5 Migraine complications
1.5.1 Chronic migraine
1.5.2 Migraine persistent state
1.5.3 Persistent aura without infarction
1.5.4 Migrainous infarction
1.5.5 Migraine-induced epileptiform attacks
1.6 Likely migraine
1.6.1 Likely migraine without aura
1.6.2 Likely migraine with aura
1.6.3 Likely chronic migraine
1.2 Diagnosis of migraine [2, 3-6]: The main diagnosis of migraine is based on the clinical manifestations. In taking the history, attention should be paid to the location, nature, degree, duration, concomitant symptoms, aura manifestations, and the effect of activities on the headache. The patient’s headache diary helps in the diagnosis. In clinical practice, secondary headaches should first be excluded before considering whether they are accompanied by other types of primary headaches. Neuroimaging is performed in the presence of (1) abnormal neurological findings, (2) acute exacerbation of headache frequency or degree, (3) change in the nature of headache, (4) new onset of headache or sudden onset of severe headache after the age of 50, (5) headache that has failed to respond to multiple treatments, and (6) other symptoms such as dizziness and numbness. EEG, TCD and other tests are not recommended as routine diagnostic tests.
The diagnostic criteria developed by the IHS are operational and are commonly used as diagnostic tools. The diagnostic criteria for migraine without aura are shown in Table 2, and those for migraine with aura are shown in Table 3. If the headache after typical aura does not match the characteristics of migrainous headache, the diagnosis should be typical aura with non-migrainous headache; if there is no headache attack after typical aura, the diagnosis should be typical aura without headache; if the aura shows weakness of limbs, the diagnosis should be hemiplegic migraine, and if there is a similar attack in the first-degree relative, the diagnosis should be familial hemiplegic migraine. If the aura manifests as weakness of the limbs, the diagnosis is hemiplegic migraine. Basal migraine was diagnosed when the aura showed involvement of nerve tissue innervated by the posterior circulatory system, such as dysarthria, vertigo, tinnitus, hearing loss, diplopia, simultaneous visual symptoms in bilateral nasal or bilateral temporal visual fields, ataxia, altered consciousness, and bilateral sensory abnormalities, rather than limb weakness [1].
If only one of the diagnostic criteria is worse than the diagnostic criteria, but there are diagnostic criteria that are not met for other headaches, the diagnosis of migraine is likely [1].
Table 2 Diagnostic criteria for migraine without aura
A At least 5 episodes meeting the characteristics of items B-D
B Headache attacks (untreated or ineffective in treatment) lasting 4 to 72 hours
C Headache characterized by at least 2 of the following: (1) unilateral, (2) throbbing, (3) moderate or severe pain, (4) aggravated by daily activities or avoidance of such activities when the headache is present
D The headache is accompanied by at least one of the following: (1) nausea and/or vomiting, (2) photophobia or phonophobia
E Cannot be attributed to other diseases
Table 3 Diagnostic criteria for typical aura with migrainous headache
A At least 2 episodes meeting the characteristics of items B-D
B Aura with at least 1 of the following manifestations without motor weakness (1) fully reversible visual symptoms, including positive manifestations (e.g., flashes of light, bright dots and lines) and/or negative manifestations (e.g., visual field defects), (2) fully reversible sensory abnormalities, including positive manifestations (e.g., pins and needles) and/or negative manifestations (e.g., numbness), (3) fully reversible verbal dysfunction
C meet at least 2 of the following: (1) isotropic visual symptoms and/or unilateral sensory symptoms, (2) at least 1 aura symptom progressive course ≥ 5 min, and/or different aura symptoms occurring in succession, course ≥ 5 min, (3) each symptom lasts 5 to 60 min
D The headache occurs at the same time as the aura symptoms or within 60 min after the onset of the aura, and the headache meets the diagnostic criteria of migraine without aura B-D
E Cannot be attributed to other diseases
2 Clinical manifestations
A migraine attack consists of four parts: the prodrome phase, the aura phase, the headache phase, and the recovery phase. Many migraine attacks do not go through all four phases. For example, patients with migraine without aura have an attack without an aura, and some migraine attacks may be followed by an aura without a headache.
2.1 Prodromal phase
In the hours and days preceding a migraine attack, some patients may exhibit certain prodromal symptoms that include mental cognitive symptoms, neurological symptoms, and nonspecific somatic complaints. Fatigue, inattention, and neck stiffness are the most common prodromal symptoms.
2.2 Aura phase
Migraine aura mostly precedes the headache, and the headache often occurs within 60 minutes of the onset of aura symptoms. The aura can also occur at the same time as the headache or, rarely, even after the headache. The aura mostly presents with completely reversible focal neurological symptoms, including visual, somatosensory, verbal, and motor deficits or irritations. Visual aura is the most common and is often bilateral. Most sensory aura are accompanied by visual symptoms.
Simple visual auras include visual field defects, dark spots, simple flashes, shimmering lights, bright spots, geometric shapes, etc. Complex auras include flashing dark spots or fortification spectra, distortion of visual objects, large and small visual objects, and “mosaic” vision. Sensory aura is usually seen in the hands and mouth, and abnormal sensation or numbness often starts in the hands and then jumps to the face, lips, tongue and other parts. Weakness aura is rare, usually unilateral, and often accompanied by sensory symptoms. In addition, aura such as aphasia, loss of use, loss of recognition, impaired consciousness, and altered perception can be seen.
Aura symptoms usually develop gradually within 5-20 minutes and disappear completely after 20-60 minutes. Different aura may appear one after another.
2.3 Headache phase
The typical headache is mostly located on one side, gradually worsens to moderately severe, and is pulsating. The headache can be aggravated by physical activity during the headache period. The headache lasts for 4 to 72 hours in adults and 1 to 72 hours in children, and in many people the headache disappears after sleep. It is important to note that migraine attacks cannot be literally assumed to be migraines, but in fact about 40% of patients have bilateral headaches.
Patients often experience a loss of appetite during the headache, about 90% of patients experience nausea, and half of patients experience vomiting during the headache. Patients are sensitive to certain sensory stimuli and are often photophobic and acoustic, and many want to lie down and rest in a quiet, unlit room at this time. The headache may be accompanied by dizziness, blurred vision, nasal congestion, hunger, abdominal discomfort, diarrhea, polyuria, pallor, abnormal sensations of heat and cold, sweating, depression, fatigue, anxiety, irritability, and difficulty concentrating.
2.4 Recovery period
After the headache, patients often feel tired and have reduced concentration, and may show signs of depression, anxiety and irritability, while some patients are more euphoric and feel particularly refreshed. Some patients may still have residual symptoms of scalp tenderness, and some may feel muscle weakness, pain, loss of appetite or hunger.
3 Epidemiology
Migraine is more prevalent in Western countries. In the United States, the annual prevalence of migraine is 1l%, and 18% of women and 6% of men have had at least one migraine attack in the previous year. The prevalence of migraine is related to age, gender, race, income and other factors.
There is a lack of relevant epidemiological data in China. Because the current international diagnostic criteria for migraine are not used, the statistics are not comparable with those of foreign countries.
4 Pathophysiology
After nearly a century of research, although some pathophysiological phenomena of migraine have been understood, the cause of headache is still unclear. To date, there is no theory that can explain the occurrence and development of migraine in a self-explanatory manner.
4.1 Genetic factors
Many migraineurs have a family history of migraine, but the molecular genetic characteristics are inconclusive, with the exception of familial hemiplegic migraine.
4.2 Aura
Aura symptoms result from abnormalities in neuronal function.
Noxious stimuli acting on the cerebral cortex of many animals can trigger a decrease in spreading cortical electrical activity at a rate of 2-6 mm/min, a phenomenon known as cortical spreading depression (CSD). In fact, the cortical depression is preceded by a transient enhancement of neuronal activity.
In 1958, Milner et al. suggested that the development of a visual aura in migraine is consistent with the process of cortical spreading depression.
4.3 Headache
Headache perception in migraineurs may be associated with activation of the head and neck pain afferent system and abnormalities in pain modulation mechanisms.
In the 1930s, Graham and Wolff et al. found that extracranial vasodilation was associated with migraine attacks. Compression of the temporal artery temporarily relieved the headache. Patients treated with ergotamine showed a simultaneous reduction in the amplitude of extracranial arterial pulsations along with headache relief. Further studies found that it was mainly the frontal branch of the superficial temporal artery that was associated with migraine attacks.
In the 1950s, Chapman et al. first identified an inflammatory mechanism in the development of migraine. They observed that subcutaneous irrigation fluid at the migraine site had inflammatory activity, the degree of which correlated with the degree of headache; after treatment with ergotamine, the inflammatory activity could be reduced. A later study by Goadsby et al. showed that calcitonin gene related peptide (CGRP) concentrations were increased in the external jugular venous blood of patients during migraine attacks; sumatriptan reduced the concentration of CGRP during migraine attacks.
Recent experimental animal studies have shown that trigeminal nerve activation can reverse the release of CGRP, substance P, neurokinin A and other active substances, triggering neurogenic inflammation. Interaction of neurotransmitters with the vascular wall leads to vasodilation, plasma protein leakage, platelet activation and further release of other inflammatory factors.
Neurogenic inflammation can sensitize the trigeminal nerve fibers (peripheral sensitisation) to non-noxious stimuli (e.g., pulsation of blood vessels) that would otherwise not be felt, which can worsen the headache. In addition, neurogenic inflammation can also cause central sensitisation. In clinical practice, headache patients sometimes experience painful sensitization (cutaneous Mlodynia) in response to harmless stimulation of normal skin (e.g., light hair brushing), which is thought to be a manifestation of central sensitisation, and the efficacy of tretinoin is greatly diminished if it is administered after the onset of this phenomenon. Central sensitization may also be related to the mechanism by which the headache persists.
Abnormalities in pain regulation mechanisms are present during migraine, and enkephalin levels in cerebrospinal fluid have been measured and found to be lower in patients during migraine attacks compared to interictal and headache-free control patients. There is a reflex link between the trigeminal nervous system and the autonomic nervous system, but the exact pathway of the link is not yet understood. It has been suggested that excitation of the caudal nucleus of the trigeminal nerve during migraine can cause vasodilation via a parasympathetic pathway originating from the superior salivary nucleus and passing through the pterygopalatine ganglion.
5 Treatment
After the diagnosis is clear, first of all, the patient should be educated to understand the pathogenesis, clinical manifestations and treatment process of headache, which can eliminate unnecessary worries about severe headache and vomiting symptoms, and also make the patient understand the existing treatment means and better cooperate with the treatment.
A regular lifestyle should be cultivated. Since migraine patients are often very sensitive to various drastic changes in their lives, it is especially important to maintain a regular sleep, diet and supplemented by appropriate exercise. Excessive stress should be avoided, but not overly relaxed.
Look for and avoid various migraine triggers. Climate changes, special diets, noisy environments, stressful exertion, and emotional changes may trigger headaches, and different patients often have different triggers.
Encourage keeping a headache diary. The diary should include the date of each headache attack, duration, intensity of the headache, accompanying symptoms, treatment, special experiences before the headache (diet, climate, environment, physical condition, etc.) and the effect of the headache on daily functions such as work life. Memory is often biased, and a headache diary helps to identify headache triggers and also provides a basis for rational selection and objective evaluation of various treatments.
Make full use of all non-pharmacological means. Drinking coffee, giving massage, cold or hot compresses may have good effects when headaches occur, and finding a quiet, dark room to rest in if possible can often provide quick relief. Professional acupuncture, massage, physical therapy, biofeedback therapy and cognitive-behavioral therapy are all very effective.
The basic principles of migraine prevention and treatment are: (1) to help patients establish scientific and correct prevention and treatment concepts and goals; (2) to maintain a healthy lifestyle; (3) to find and avoid various migraine triggers; (4) to make full use of non-pharmacological interventions, including massage, physical therapy biofeedback therapy, cognitive behavioral therapy and acupuncture; (5) pharmacological treatment includes two categories: acute attack treatment and preventive treatment. Chinese medicine is widely used, but more evidence-based medical evidence is needed [1].
Pharmacological treatments include two major categories: acute exacerbation treatment and prophylactic treatment.
5.1 Acute exacerbation treatment [1-10]
Acute attack treatment is aimed at pain relief, elimination of concomitant symptoms and restoration of daily function, and is divided into nonspecific and specific treatments. Nonspecific therapeutic drugs can be used for a variety of pains, while specific therapeutic drugs are effective only for certain types of headaches such as migraine and not for other headaches and pains in other areas.
Non-specific therapeutic drugs include: (1) analgesics and non-steroidal anti-inflammatory drugs; (2) sedatives such as barbiturates; and (3) opioids. The first class of drugs is most commonly used clinically, such as aspirin, acetaminophen, ibuprofen, naproxen, anti-inflammatory pain, tofenamic acid, etc. There are many kinds of drugs. Some of these drugs are commonly used over-the-counter, such as acetaminophen and caffeine compound, with few adverse reactions. The latter two categories are easily addictive and should be used with caution, and can be applied occasionally in severe cases where other treatments are ineffective.
Specific therapeutic drugs include: ① Ergot preparations: ergotamine and dihydroergotamine. Ergotamine caffeine is commonly used in China, which is a compound preparation of ergotamine tartrate and caffeine; ② Trutane-type drugs: a variety of drugs and dosage forms have been marketed abroad, and oral dosage forms of sumatriptan and zolmitriptan are available in China. Tritans are 5-HTlB/1D receptor agonists, and some can agonize 5-HTlF receptors. They are mainly used to control acute attacks of headache by constricting the blood vessels in the head, inhibiting the neuronal and neurogenic inflammation around the trigeminal system, and inhibiting the transmission through the secondary neurons of the trigeminal system, which affect the activation process of the trigeminal and pain afferent system.
The choice of medication for acute attacks needs to be based on the severity of headache, concomitant symptoms, frequency of attacks, past drug response and past medical history, and the patient’s wishes. For many mild to moderate migraine attacks, over-the-counter analgesic medications are safe and effective; however, more severe headache attacks with greater impact on daily functioning should be preferred to specific treatment, and the degree of impact of migraine on daily functioning can be clinically assessed by a number of scales (e.g., the MIDAS scale). If accompanied by severe nausea and vomiting, extra gastrointestinal administration can be used. There are various dosage forms such as subcutaneous and intravenous injection, nasal spray, oral disintegration and anal suppository in foreign countries, and these dosage forms also have the advantage of short duration of action, but there is a lack of these drugs in China at present, and they need to be developed and introduced urgently. Early and adequate use of drugs after the onset of headache can better control the headache, but if the headache attacks frequently, this approach is not appropriate. However, if headache attacks are frequent, this approach is inappropriate because the use of drugs in the acute phase of treatment should not exceed 2-3 days per week, otherwise it may lead to drug abuse headache. There is a significant uncertainty in the response to headache attacks and medications, and a medication can be considered ineffective only after it has been used in sufficient quantity for two consecutive attacks. When choosing drugs, attention should also be paid to the adverse effects of drugs, for example, all atopic therapeutic drugs have the effect of constricting blood vessels and may constrict coronary arteries, so they should not be used in patients with coronary heart disease, ischemic cerebrovascular disease, and poorly controlled hypertension.
Antiemetics and drugs that enhance gastrointestinal motility not only treat the concomitant symptoms of headache attacks, but also facilitate the absorption of other drugs and the treatment of headache. These drugs include gastrofacial, morpholine, prochlorperazine, haloperidol, etc. Corticosteroids can also be used for severe migraine attacks.
5.2 Prophylactic treatment [1, 3-7,10,11]
The aim of prophylactic treatment is to reduce the frequency of migraine attacks, shorten the duration of migraine attacks, and reduce the severity of migraine attacks.
Migraine prophylaxis mostly requires daily medication, and the currently used prophylactic medications often have some adverse effects at the effective dose, so not all migraine patients need prophylaxis. Prophylactic treatment may be considered in the following cases: recurrent headaches that seriously affect daily life; acute treatment is ineffective or cannot be administered due to adverse effects and contraindications; frequent migraine attacks that may lead to drug overdose and dependence; special needs of the patient, etc.
Commonly used drugs for preventive treatment of migraine include: ① β-adrenergic receptor blockers: not all β-blockers have the effect of migraine prevention, propranolol, nadolol, atenolol, metoprolol, timolol, etc. have certain effect; ② antidepressants: such as amitriptyline, fluoxetine, etc.; ③ calcium antagonists: such as flunarizine, nimodipine, verapamil, etc.; ④ antiepileptic drugs. Such as sodium valproate. Some foreign countries have reported that sodium bivalate, topiramate, gabapentin, etc. are effective; ⑤ 5-HT antagonists: including benzothiazide and methicillin, etc.; ⑥ Others: local injection of botulinum toxin A, coenzyme Q10, high-dose vitamin B2, etc. can also be used for migraine prophylaxis.
All the above-mentioned types of prophylactic drugs are only effective for some patients, and different patients often need different drugs.
Because the mechanism of drug prophylaxis for migraine is not known, the choice of medication can often feel rather blind. Combining the patient’s other medical history and the mechanism of the medication can help in the selection of medication. If the patient has a history of hypertension and angina pectoris, beta-blockers or calcium antagonists can be tried preferentially; if accompanied by depressed mood, antidepressants should be considered first.
The following should be noted for the use of prophylactic medications: Pain medication abuse must be ruled out before starting prophylaxis. Because none of the available prophylactic medications are effective for substance abuse headaches; all medications should be started in small doses and gradually increased. All medications should be increased gradually, starting with small doses, until they become effective or until the maximum dose of the medication is reached or until unacceptable adverse effects occur: there is a delay in the onset of action of the medication, and each medication should be tried for a sufficient period of time, usually 2-6 months, with many medications taking effect within 4 weeks and showing more pronounced effects over the next 3 months; interference with other medications should be avoided when trying prophylactic medications; pregnancy should be avoided during prophylaxis It is advisable to remind patients not to expect too much from preventive medication; there is no medication that can completely stop migraine attacks, and it is considered effective if the number of headache attacks is reduced by half.
5.3 Traditional Chinese medicine treatment [12]
5.3.1 Acupuncture for migraine and research
Acupuncture has good clinical efficacy in the treatment of migraine. Wang [13] studied the mechanism of acupuncture for migraine, and 40 rats were divided into normal control and model control groups and treatment groups, and acupuncture control and treatment groups. Plasma endothelin ET and neuropeptide Y-NPY) levels in jugular venous blood were determined by using a release immunoassay. The results showed that the levels of ET and NPY were significantly lower in the model control group compared with the normal control group (P