The etiology of migraine is unclear and may be related to the following factors.
Genetic factors
Approximately 60% of migraine patients have a family history of migraine, and their relatives are at 3-6 times greater risk of developing migraine than the general population. Consistent Mendelian inheritance patterns have not been found in familial migraine patients, reflecting the interaction of different epistatic rates and polygenic genetic characteristics with environmental factors. Familial hemiplegic migraine is clearly an autosomal dominant inheritance with a high abnormal epistasis and has been localized to three disease loci including 19p13 (associated with mismatched mutations in the brain-expressed voltage-gated P/Q calcium channel gene), 1q21 and 1q31.
Endocrine and metabolic factors
The disease is more frequent in females than males, with onset in adolescence, easy onset during menstruation, and reduced or stopped during pregnancy or after menopause. This suggests that endocrine and metabolic factors are involved in the development of migraine. In addition, abnormalities in the metabolism of 5-hydroxytryptamine (5-HT), norepinephrine, substance P and arachidonic acid can also affect the occurrence of migraine.
Dietary and psychiatric factors
Migraine attacks can be triggered by certain foods and medications, including tyramine-containing cheeses, nitrite-containing preservatives in meats and cured foods, phenylethylamine-containing chocolate, food additives such as monosodium glutamate (MSG), red wine and wine. Medications include oral contraceptives and vasodilators such as nitroglycerin. Some environmental and mental factors such as stress, overwork, emotional stress, too much or too little sleep, menstruation, and bright light can also trigger it.
Pathogenesis
The pathogenesis of migraine is not well understood, but the following theories are the main ones.
Vascular theory
The traditional vascular theory suggests that migraine is a primary vascular disease. Intracranial vasoconstriction causes migraine aura symptoms, followed by extracranial and intracranial vasodilatation and production of vasoactive peptides in the perivascular tissue leading to sterile inflammation resulting in pulsatile headache. Local compression of carotid and superficial temporal arteries, and vasoconstrictor ergot alkaloids such as ergotamine can relieve episodic headache support this theory. Neuroimaging development of TCD, PET and other clinical applications further developed the vascular origin theory, suggesting that aura and aura-free migraine are the same disease with different degrees of vasospasm. Various neurons have different sensitivities to ischemia, and aura symptoms appear due to vasoconstriction and reduced blood flow after which neurons in the visual cortex are most sensitive to ischemia, so visual aura appears first, and then more and more neuronal functions are affected, and then other neurological symptoms such as numbness of fingers gradually appear.
Neurological theory
The neurological theory suggests that changes in neurological function during a migraine attack are primary and changes in blood flow are secondary. Migraine aura is caused by extended cortical depression (CSD), which is a band of inhibitory neuroelectrical activity originating in the posterior cerebral cortex (occipital lobe) caused by various noxious stimuli, extending at a rate of 2-5 mm/min to the adjacent cortex, accompanied by an extended reduction in blood flow. CSD is a good explanation for migraine aura symptoms. In addition, 5-hydroxytryptamine (5-HT) is involved in headache onset. At the beginning of a headache attack, 5-HT is released from platelets and acts directly on the small intracranial blood vessels causing them to constrict and attach to the vessel walls. When the plasma 5-HT concentration decreases, it acts on the large arteries and the tensional constricting effect disappears, and the blood vessel wall dilates. 5-HT is both a neurotransmitter and a humoral mediator, affecting both nerves and blood vessels. Tretinoin drugs for migraine are central 5-HT receptor agonists or partial agonists. This confirms the involvement of neurological dysfunction in the process of migraine attacks.
Trigeminal vascular theory
The anatomical and physiological basis of this theory is the trigeminal vascular complex. Intracranial pain-sensitive tissues such as cerebral blood vessels, meningeal vessels, and venous sinuses have perivascular nerve fibers that enter the trigeminal ganglion with the ophthalmic branch of the trigeminal nerve or enter the posterior roots of the 1 and 2 cervical nerves (C1 and C2) from the posterior cranial fossa; both of them send nerve fibers to the trigeminal nerve cervical complex, which consists of the caudal end of the nucleus of the spinal bundle of the trigeminal nerve and the posterior horn of C1 and C2, after the transposition of the trigeminal ganglion and C1 and C2 spinal ganglia; The trigeminal cervical complex emits nerve fibers that project to the thalamus via brainstem crossings. The peripheral pain mechanism of this doctrine suggests that trigeminal ganglion damage may be the neural basis for migraine production. When the trigeminal ganglion and its fibers are stimulated, it can cause increased release of substance P (SP), calcitonin gene-related peptide (CGRP), and other neuropeptides. These active substances acting on the adjacent cerebral vascular wall can cause vasodilation and pulsatile headache, and also increase vascular permeability and plasma protein leakage, producing sterile inflammation and stimulating nociceptive fibers to the center, forming a vicious circle.
Pathophysiology
Intracranial pain-sensitive tissues such as cerebral blood vessels, meningeal vessels, venous sinuses, their perivascular nerve fibers and trigeminal nerve may be the physiological basis of migraine occurrence and nociceptive transmission pathways. Electrical stimulation of the trigeminal ganglion can lead to aseptic inflammation of the dural vessels. The trigeminal vascular reflex theory of migraine suggests that migraine is caused by the release of substance P (SP) and other neurotransmitters from the afferent fiber endings of the trigeminal nerve, and the efferent nerve acts on the intracranial and extracranial vessels, causing headache and vasodilation. The most prominent neuropeptide associated with the trigeminal system is calcitonin gene-related peptide (CGRP), followed by substance P (SP), and neurokinin A (NKA). Substance P is a neurotransmitter that transmits and lowers the pain threshold and acts synergistically with neurokinin A (NKA), while calcitonin gene-related peptide (CGRP) has a strong vasodilating effect and causes headache by dilating blood vessels.
Clinical manifestations
Frequent attacks of migraine will affect the patient’s life and work, most directly affecting sleep, as lack of sleep makes the patient unrefreshed during the day, and work is greatly affected. Moreover, some patients often have attacks as soon as they work, which is very delayed. At the same time, when people suffer from headache disease for a long time, their personality changes and they often become irritable. In addition, because the headache is not cured for a long time, life is greatly affected, psychological fragility, loss of confidence, and over time, it will have a negative impact on people’s cardiovascular and cerebrovascular, and clinically, cerebral thrombosis, hypertension and cerebral hemorrhage are also more common after headache attacks.
The following are the clinical manifestations of the main types of migraine.
1.Migraine without aura
Migraine without aura is the most common type of migraine, accounting for about 80%. There may be no obvious aura symptoms before the onset of migraine, but some patients have mental disorder, fatigue, yawning, loss of appetite and general discomfort before the onset of migraine, and pain can be triggered by menstruation, alcohol consumption and hunger on an empty stomach. The headache is slowly aggravated, with recurrent episodes of frontotemporal pain on one side or both sides, which is pulsating, and the symptoms are complicated by contraction of the neck muscles when the pain persists. It is often accompanied by nausea, vomiting, photophobia, phonophobia, sweating, general discomfort, and scalp tenderness. Compared with migraine with aura, migraine without aura has a higher frequency of attacks, which can seriously affect patients’ work and life, and often requires frequent treatment with painkillers. medication-overuse headache”.
2.Migraine with aura
Migraine with aura accounts for about 10% of migraineurs. There may be precursory symptoms such as tiredness, inattention and yawning for hours to days before the attack. The most common aura is visual aura, such as blurred vision, dark spots, flashes of light, bright spots and bright lines, or distortion of vision; followed by sensory aura, with sensory symptoms mostly distributed in the face-hand region; speech and motor aura are rare. Aura symptoms generally develop gradually within 5-20 minutes and last no more than 60 minutes; different aura can appear one after another. Headache occurs at the same time as or within 60 minutes after the aura and is manifested as a one-sided or bilateral frontotemporal or retro-orbital pulsating headache, often accompanied by nausea, vomiting, photophobia or phonophobia, pallor or sweating, polyuria, irritability, odor terror and fatigue, etc. Head and facial edema and temporal artery prominence are seen. The headache can be aggravated by activity and relieved by sleep. The pain usually peaks in 1~2 hours and lasts for 4~6 hours or more than 10 hours, and can last for several days in severe cases. After the headache subsides, there are often fatigue, lethargy, irritability, weakness and poor appetite.
(1) Migraine headache with typical aura: It is the most common type of migraine with aura, and the aura is completely reversible visual, sensory or verbal symptoms, but no physical weakness. Migrainous headache with typical aura is defined as a headache that occurs simultaneously with or within 60 minutes after the aura and is consistent with the characteristics of migraine. If the headache occurs at the same time as the aura or within 60 minutes after the aura and is not consistent with migraine, it is called non-migraine headache with typical aura; when the headache does not occur within 60 minutes after the aura, it is called typical aura without headache. The latter two should be distinguished from transient ischemic attacks.
(2) Hemiplegic migraine hemiplegic migraine: It is rare clinically. In addition to motor weakness, the aura should include one of three types of aura: visual, sensory and verbal. The aura lasts from 5 minutes to 24 hours and is completely reversible. If at least one of the first- or second-degree relatives of a person with hemiplegic migraine has a migraine aura that includes motor weakness, the migraine is familial hemiplegic migraine; if not, it is called sporadic hemiplegic migraine.
(3) Basal migraine: The aura symptoms clearly originate from the brainstem and/or both cerebral hemispheres, and are clinically seen as dysarthria, vertigo, tinnitus, hearing loss, diplopia, simultaneous visual symptoms in the nasal and temporal visual fields of both eyes, ataxia, impaired consciousness, and simultaneous sensory abnormalities bilaterally, but no motor weakness symptoms. Headache with migraine characteristics, often accompanied by nausea and vomiting, occurs at the same time as or within 60 minutes of the aura.
3.Retinal migraine
Retinal migraine is a recurrent, fully reversible monocular visual disturbance, including flickering, dark spots or blindness, with migraine attacks, with normal interictal ophthalmologic examination. Unlike basal migraine, in which visual aura symptoms often involve both eyes, retinal migraine visual symptoms are limited to one eye and lack neurological deficits or irritation originating in the brainstem or cerebral hemispheres.
4. Childhood periodic syndrome
Childhood periodic syndrome, which is often the precursor of migraine, can be considered as migraine equilibrium, and can be seen clinically as periodic vomiting, recurrent abdominal pain with nausea and vomiting, i.e. abdominal migraine, and benign childhood episodic vertigo. The attacks are not accompanied by headache, and migraine may occur over time.
Complications of migraine
(1) Chronic migraine: Migraine headache can be considered as chronic migraine if the headache attacks are more than 15 days per month for 3 months or more, and headache caused by drug overdose is excluded.
(2) Migraine persistence: Migraine attacks lasting ≥ 72 hours and with severe pain, but there may be a brief period of remission obtained by sleep or medication application in between.
(3) Persistent aura without infarction: Patients with migraine with aura have one aura or multiple aura symptoms lasting more than 1 week in one attack, mostly bilateral; other symptoms of this attack are similar to those of previous attacks; neuroimaging is required to exclude cerebral infarction lesions.
(4) Migrainous infarction: In rare cases, ischemic infarction in the corresponding blood supply area of the skull occurs after migraine aura symptoms, which often lasts for more than 60 minutes, and the ischemic infarct lesion is confirmed by neuroimaging, which is called migrainous infarction.
(5) Migraine-induced epileptic seizure: In rare cases, migraine aura symptoms can trigger an epileptic seizure, and the epileptic seizure occurs during or within 1 hour after the aura symptoms.
Oculomotor paralysis migraine
Ophthalmoplegic migraine is characterized by recurrent migraine-like headaches, with headache attacks occurring simultaneously with or within 4 days of ocular muscle paralysis on the headache side. In some cases, MRI-enhanced scans may indicate recurrent demyelination of the affected motor nerve. Therefore, there is a tendency not to consider oculomotor palsy migraine as a subtype or variant of migraine.
Differential diagnosis
Cluster headache
Cluster headache, also known as histamine headache, is a rare clinical condition. It presents as a series of intense, transient, severe unilateral drilling pains. The headache is most often confined and fixed to one orbital, retrobulbar, and frontotemporal region. The onset is sudden and unpredictable, with a fixed duration of 15 minutes to 3 hours and episodes ranging from 1 every other day to 8 per day. The pain is severe, often unbearable, with facial flushing, conjunctival congestion, lacrimation, runny nose, and nasal congestion, mostly without nausea or vomiting. The age of onset is usually later than that of migraine, averaging 25 years old, with a male to female ratio of about 4:1.
Tension-type headache
Tension-type headache: It is also called muscle contraction headache. The headache is more diffuse and can be located in the forehead, both temporal, parietal, occipital and cervical areas. The nature of the headache is often dull, with a feeling of pressure and tightness in the head. The headache is often persistent, but in some cases it may be paroxysmal or throbbing. It is rarely accompanied by nausea and vomiting. Most patients have pressure points on the scalp and neck, and massage on the head and neck can relieve the headache. It is mostly seen in young and middle-aged women. Emotional disorders or psychological factors can aggravate headache symptoms.
Painful ophthalmoplegia
Painful ophthalmoplegia is an inflammatory disease characterized by headache and ophthalmoplegia involving the idiopathic orbit and cavernous sinus. It is a paroxysmal, intractable swelling, stabbing or tearing pain behind the eye and around the orbit, accompanied by motility, talipes and/or adductor nerve palsy. The disease can resolve on its own after a few weeks, but is prone to recurrence. Appropriate glucocorticoid therapy can relieve pain and ocular muscle palsy.
Symptomatic migraine
Symptomatic migraine is caused by head and neck vascular lesions such as ischemic cerebrovascular disease, cerebral hemorrhage, unruptured saccular aneurysm and arteriovenous malformation; headache caused by non-vascular intracranial diseases such as intracranial tumor; headache caused by intracranial infection such as brain abscess and meningitis. These secondary headaches can also be clinically manifested as migraine-like headaches, which may be accompanied by nausea and vomiting, but without the typical migraine attack process, and most cases have focal neurological deficits or irritation symptoms, and cranial imaging can show the lesion. Headache due to disorders of the internal environment such as hypertensive crisis, hypertensive encephalopathy, eclampsia or pre-eclampsia may present as bilateral throbbing headache, and the timing of the headache is closely related to elevated blood pressure.
Drug overdose headache
Overdose headache is a secondary headache. Overdose mainly refers to too frequent and regular use, such as a fixed number of days per month or week. Clinically, it is common to take ergotamine, treprostin, and opiates regularly for ≥10 days per month or simple painkillers for ≥15 days for more than 3 months, and the headache occurs or worsens significantly during the above-mentioned drug overdose. Headache occurrence is drug-related and may be migraine-like or mixed headache of both migraine and tension-type headache nature, with the headache resolving or returning to the original headache pattern within 2 months after drug discontinuation. Overdose headache is ineffective for preventive treatment measures, so it is extremely important to make a proper diagnosis.
Treatment of the disease
Treatment of migraine is aimed at reducing or ending the headache attack, relieving the accompanying symptoms, and preventing the recurrence of the headache. Treatment includes both pharmacological and non-pharmacological treatments. Non-pharmacological treatment is mainly physical therapy, which can be used to relieve stress, maintain a healthy lifestyle and avoid various migraine triggers by using magnetic therapy, oxygen therapy and psychological guidance. The pharmacological treatment is divided into the treatment during the attack period and the preventive treatment. To achieve the best results, medication should usually be taken immediately at the onset of symptoms. Medications include non-specific analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids.
and opioids, and specific medications such as ergots and traptans. Drug selection should be individualized according to the degree of headache, concomitant symptoms and previous medications.
1. Mild to moderate headache: NSAIDs such as acetaminophen, naproxen and ibuprofen alone can be effective, but if they are not effective, migraine-specific drugs should be used. Opioids such as pethidine are also effective for acute attacks of confirmed migraine, but because of their addictive properties, they are not recommended for migraine treatment routinely.
2. Moderate-severe headache: Migraine-specific therapeutic drugs such as ergot preparations and traptans can be used directly to improve the symptoms as soon as possible, and some patients who have severe headache but have responded well to NSAIDS in previous attacks can still use NSAIDS.
(1) Ergot agents: non-selective agonists of 5-HT1 receptors, such as ergotamine and dihydroergotamine (DHE), which can terminate the acute attacks of migraine.
②Triptans: They are selective agonists of 5-HT1B/1D receptors, which may play an analgesic role by constricting cerebral blood vessels and inhibiting neuropathic transmission in peripheral nerves and secondary neurons of the “trigeminal cervical complex”. Commonly used drugs include sumatriptan, naratriptan, rizatriptan, zolmitriptan, and almotriptan. Adverse effects of ergot and treprostatin drugs include nausea, vomiting, palpitations, irritability, anxiety, peripheral vasoconstriction, and large amounts of long-term application can cause hypertension and ischemic necrosis of the limbs. The above two classes of drugs have potent vasoconstrictive effects and are contraindicated in patients with severe hypertension, heart disease and pregnant women. In addition, if ergot and treprostatin drugs are applied too frequently, they can cause drug overuse headache. To avoid this, it is recommended to use the drugs no more than 2 to 3 days per week.
3. Concomitant symptoms: Nausea and vomiting are prominent concomitant symptoms of migraine and are also common adverse drug reactions, so the combination of antiemetic (such as metoclopramide 10mg intramuscular injection) is necessary. Benzodiazepines may be given to sedate and put the patient to sleep in cases of irritability.
Prognosis of the disease
The prognosis for most migraine patients is good. Migraines may gradually resolve with age, and some patients may stop having migraine attacks by the age of 60 to 70.
Disease management
There is no specific treatment that can eradicate migraine, but the most effective treatment is prevention by avoiding triggers during the interval of migraine. The details are as follows.
1 Stay away from tyraminic acid-based foods
Tyramine is the main trigger of vasospasm, which can cause headache attacks. These foods include cheese, chocolate, citrus foods, marinated sardines, chicken liver, tomatoes, milk and lactic acid drinks.
2. Reduce the intake of alcohol
All alcoholic beverages can trigger headaches, especially red wine contains more headache-inducing chemicals. If you must drink, it is best to choose vodka, white wine such as colorless wine.
3.Learn to reduce stress
Relax, choose a warm bath, do yoga and other relaxation exercises can avoid headaches.
4.Regular exercise
For people who have migraine, exercises that focus on breathing training and breath regulation (such as yoga and qigong) can help patients stabilize the autonomic nervous system and reduce symptoms such as anxiety and muscle tightness.
5. Regularity of life
Create a quiet environment, maintain a regular routine, and go to bed and get up regularly even on holidays.