Migraine

Migraine is a type of primary headache. In typical cases, the attack lasts from 4 to 72 hours, while the symptoms may be pronounced. Often the pain is one-sided, throbbing, aggravated by physical exertion, and may also be accompanied by symptoms such as nausea, sensitivity to light, sound, odors. 25% of patients develop precursors of an epileptic seizure, more often before, but sometimes after, a headache attack. The diagnosis is made on the basis of clinical data. Triptans, dihydroergotamine, antiemetics and analgesics are used in the treatment. Prevention consists of lifestyle correction (e.g., sleep or diet) and the use of medications (e.g., beta-blockers, amitriptyline, topiramate, divalproex, monoclonal antibodies).

Epidemiology of migraine

Migraine is the most common cause of recurrent headache of moderate to severe intensity; in the United States, the prevalence of this pathology for 1 year is 18% in women, 6% in men. Migraine usually begins at a young age, subsequently the degree of its intensity changes over the years; After 50 years, the disease often regresses. Some studies have shown a hereditary predisposition to the development of migraine.

Based on data from a survey of veterans of conflicts in Iraq and Afghanistan, an assumption is made about the possibility of developing migraine after head injuries.

Pathophysiology of migraine

It is believed that migraine is a neurovascular headache syndrome in which there is a change in the functional activation of the central nervous system (activation of the nuclei of the brain stem, hyperexcitability, and then spreading depression of the cerebral cortex) and involvement in the process of the neurovascular complex of the trigeminal nerve (the release of neuropeptides leads to painful inflammation of the vessels of the skull and dura mater).

A large number of factors have been identified that can provoke a migraine attack, for example:

• Drinking red wine
• Irregular meals
• Strong irritants (e.g., flickering lights, strong odors)
• Weather changes
• Sleep deprivation
• Stress
• Hormonal factors, especially those associated with menstruation
• Certain food products

Trigger products vary from person to person.

In some cases, a migraine attack or worsening of its course can be caused by a head injury, neck pain or temporomandibular joint dysfunction.

Fluctuations in estrogen levels are also a possible trigger factor. In many patients, the debut of migraine coincides with menarche, severe attacks develop during menstruation (the so-called menstrual migraine), and during menopause there is a deterioration. Most women have migraine remission during pregnancy (although in some cases there is a deterioration during the 1st or 2nd trimester of pregnancy); They are exacerbated after the birth of the child, when estrogen levels drop sharply.

Taking oral contraceptives and other hormonal drugs sometimes provokes or increases the intensity of migraine attacks, and is also a risk factor for stroke in women suffering from migraine with aura.

Familial hemiplegic migraine is a rare subtype of migraine that is associated with defects in genes located on chromosomes 1, 2, and 19. The role of the genetic component in the more common forms of migraine is currently being studied. In some families, the manifestations of migraine vary considerably, causing headache in some family members in the first place, dizziness, hemiplegia or aura in others. These data indicate that that migraines may actually be a more generalized illness rather than just a headache.

Symptoms and signs of migraine

Often foreshadows attacks prodromal period (the feeling that migraine begins). The prodromal period may include mood swings, neck pain, cravings for a specific food, loss of appetite, nausea, or a combination of these symptoms.

Approximately 25% of patients have precursors that precede seizures. Auras are transient neurological disorders that can affect sensitivity, balance, motor coordination, speech, or vision; They last from a few minutes to an hour. After the onset of a headache episode, the aura may persist. Most often, auras develop visual disturbances (flashes of light, arcs of flickering lights, bright zigzags, scotoma). Less common are paresthesia and numbness (usually starting in the hand and then moving to the arm and face), speech disorders, and transient brainstem dysfunction (manifested by ataxia, confusion, or even stunning). In some patients, the aura develops almost against the background of the absence or minor headache.

The intensity of the headache varies from moderate to severe, the attacks last from 4 hours to several days, with regression in typical cases after sleep. Most often, the pain is one-sided, but it can spread to both halves, has a pulsating character, the most common localization is the frontotemporal region.

However, migraine develops not only a headache. It is accompanied by a range of symptoms, such as nausea (sometimes vomiting), photophobia, phonophobia and osmophobia. During an attack, patients complain of difficulty concentrating. Normal physical activity usually increases the intensity of headaches; That is why, as well as due to the development of photo- and phonophobia, patients prefer to be in a dark room during an attack, with a minimum number of extraneous sounds. In severe cases, seizures practically incapacitate patients, preventing them from working and disrupting family life.

The frequency and intensity of seizures vary widely. Many patients have several types of headache, including less severe attacks that are not accompanied by nausea or photophobia; According to the clinical picture, they may resemble tension headaches, but they are, in fact, a form of migraine.

Chronic migraine

Patients with episodic migraine may subsequently develop chronic migraines. In such patients, headache attacks occur ≥ 15 times a month. Previously, this pathology was called a mixed, or combined, headache, since it had features of both migraine and tension headache. Headaches of this kind often occur in patients who abuse the use of drugs to relieve headache attacks.

Other symptoms

With other, rarer forms of migraine, other symptoms may develop:

• In basilar migraine, there is a combination of dizziness, ataxia, visual field limitations, sensory disturbances, focal weakness and changes in the state of consciousness.
• In the hemiplegic form of migraine (can be sporadic or familial), unilateral paresis develops.

Diagnosis of migraine

• Clinical Evaluation

When diagnosing migraines, they rely on characteristic symptoms and the absence of pathology during an objective examination, which includes a detailed assessment of the neurological status.

Warning features that should be noted and which indicate the presence of a different pathology (even in patients with verified migraine) include the following:

• A headache that reaches a peak of intensity within a few seconds (like a "thunderclap")
• Debut over the age of 50
• Headache attacks with increasing intensity and/or frequency for several weeks or more
• History of malignancy (brain metastases) or immunodeficiency disorder (e.g., HIV infection, AIDS)
• Fever, meningism, altered state of consciousness, or a combination thereof
• Persistent focal neurological symptoms
• Congestive optic disc
• A distinct change in the nature of headaches

In patients with a characteristic clinical picture and the absence of the above-mentioned warning signs, additional examination is not required. In the presence of "red flags", an examination is often necessary, including an MRI and, in some cases, a lumbar puncture.

The most common diagnostic errors include:

• Ignoring the fact that migraines can cause bilateral pain, which is not always described as throbbing.
• Misdiagnosis of migraine as sinus headache or excessive eye strain occurs because there are no autonomic and visual symptoms of migraine.
• The assumption that any episode of headache in a patient with a verified migraine is a migraine attack (a "thunderclap" headache or a change in the nature of a habitual headache may indicate a new, potentially serious pathology).
• Migraine with aura can be mistaken for a transient ischemic attack, especially if the aura occurs without a headache, in the elderly.
• Diagnosing a sudden headache as a migraine, since it disappears after taking triptan (taking triptans relieves headaches and subarachnoid hemorrhage).

Some rare disorders can mimic migraines with aura:

• Dissection of the carotid or vertebral artery
• Cerebral vasculitis
• Moyamoya disease
• CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
• MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like seizures)

Prognosis for migraine

In some patients, migraine attacks are infrequent and quite tolerable. In others, migraine occurs as a debilitating ailment, leading to frequent episodes of disability, loss of ability to be productive and a significant decrease in the quality of life.

Treatment of migraine

• Eliminate obvious triggers
• Relaxation techniques, yoga or behavioral interventions
• With unexpressed attacks - acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs)
• In the case of acute attacks, it is recommended to take triptans, lasmiditan, hepants (antagonists of calcitonin-gene-linked peptide [ubrohepant, etc.]) or dihydroergotamine together with an antiemetic - a dopamine antagonist
• Neuromodulatory devices for the treatment of acute attack and prevention

A detailed explanation to patients of the features of a disorder such as migraine helps them understand that, despite the incurability of this pathology, it is possible to control it, which encourages patients to take a more active part in treatment.

The patient is advised to keep a headache diary, which should note the number and time of onset of seizures, provoking factors and reaction to medications. The identified provoking factors are eliminated as much as possible. However, eliminating triggers may be exaggerated.

For patients who use drugs for the treatment of acute migraine attacks (analgesics, triptans, lazmiditans, opioids) often (for example, > 2 days / week), especially with abusive headache, prophylactic drugs (see table Drugs for the treatment of migraine) should be combined with a program to stop taking analgesics that have previously been abused.

Clinicians sometimes recommend the use of behavioral psychotherapy (biofeedback, stress management, psychotherapy) in situations where the main cause of headache is stress, as well as excessive use of analgesics.

Yoga can reduce the frequency and intensity of headaches; It increases vagal tone and reduces sympathetic, thereby improving the autonomic balance of the heart. Relaxation techniques can reduce the activity of the sympathetic nervous system, reduce muscle tension, and alter the activity of brain waves.

Treatment for acute migraine depends on the frequency, duration, and severity of the attacks. It may include analgesics, antiemetics, triptans, and/or dihydroergotamine. If patients want to avoid drug treatment or in the case when drug treatment has been ineffective, then neuromodulatory therapy can sometimes be used to stop acute attacks and prevent them.

Acute attacks

For migraine attacks of mild to moderate intensity, NSAIDs or acetaminophen are prescribed.

If these drugs are ineffective, triptans or dihydroergotamine should be considered. Effective headache relief with triptans or dihydroergotamine should not be considered as a diagnostic criterion for migraine, since these same drugs can relieve pain in subarachnoid hemorrhage or other organic brain lesions.

If mild seizures worsen, or if seizures are severe from the onset, triptans or dihydroergotamine may be used. With severe nausea, a combination of triptan with an antiemetic is effective, also taken at the beginning of the attack.

They are selective agonists of serotonin 1B-, 1D-receptors. Not being inherently analgesics, triptans specifically block the release of neuropeptides, which provoke a headache attack. These drugs are most effective when taken at the very beginning of the attack. They are available in forms for oral administration, intranasal and subcutaneous; Forms for subcutaneous administration are more effective, but give more side effects. Excessive use of triptans can also lead to the development of abusive headaches. Taking triptans and dihydroergotamine can provoke spasm of the coronary arteries, and therefore these drugs are contraindicated in patients with coronary heart disease or malignant arterial hypertension; With caution they should be used in elderly patients and in the presence of risk factors for vascular pathology. Alternatives are ubrohepant and rimegepant, which belong to hepants (low molecular weight receptor antagonists of the calcitonin gene encoded peptide [CGRP]).

When triptans or dihydroergotamine are contraindicated due to cardiovascular disease, lasmiditan (a novel selective serotonin [5-HT] 1F receptor agonist) or a hepant such as ubrohepant or rimegepant may be prescribed. Lasmiditan, which has a much greater affinity for serotonin 1F receptors than for 1B receptors, has no contraindications from the cardiovascular system. (Triptans induce vasoconstriction by activating 5-HT1B receptors.) At the moment, there are no special cardiovascular precautions or contraindications when using hepants and there are no serious cardiovascular and gastrointestinal effects.

Antiemetic drugs as monotherapy (e.g., metoclopramide, prochlorperazine) can also stop an attack of mild to moderate headaches. If you are intolerant to triptans and other vasoconstrictor drugs, it is possible to use prochlorperazine in the form of suppositories (25 mg) or tablets (10 mg).

Strong evidence supports the use of neuromodulatory devices for the treatment and prevention of attacks in chronic migraines.

Seizures that do not stop

Intravenous infusion of large volumes of fluid (e.g., 1 to 2 L of 0.9% saline) may help relieve headaches and improve well-being, especially in patients with dehydration as a result of vomiting.

In severe prolonged attacks, intravenous administration of dihydroergotamine in combination with a dopamine receptor antagonist (e.g., metoclopramide 10 mg intravenously, prochlorperazine 5-10 mg intravenously) is effective. Dihydroergotamine is also available in intranasal and subcutaneous forms. An inhalation form is currently under development.

Opioids should be used only as a last resort, when other means are ineffective.

Chronic migraine

In the treatment of chronic migraine, the same drugs are used as for episodic migraine, including monoclonal antibodies that block CGRP. In addition, there is strong evidence in favor of onabotulinum toxin A and topiramate.

Evidence supports the use of neurostimulation to treat and prevent attacks in chronic migraines. Non-invasive options include supraorbital stimulation, vagus nerve stimulation, monopulse transcranial magnetic stimulation, and remote electrical stimulation.

Neuromodulatory treatment

Neuromodulatory therapies that affect brain activity through electric currents or magnetic fields can be non-invasive, using commercially available devices. Such methods are also used to treat and prevent seizures.

Non-invasive transcranial magnetic stimulation using a handheld device applied to the back of the head can relieve acute migraines. A device that uses a bandage that provides painless electrical stimulation of the skin (called remote electrical neuromodulation) can relieve acute migraine pain. It is also effective to use a portable device that provides non-invasive stimulation of the vagus nerve.

For the treatment of acute migraine attacks (with or without aura) or to reduce the frequency of attacks in some cases, patients ≥ 18 years of age can use trigeminal nerve stimulation using a device applied to the forehead.

Non-invasive neuromodulatory devices are not accompanied by significant side effects. Invasive treatments are generally only available at specialized centers and are at greater risk than non-invasive treatments.

Prevention of migraine

Daily preventive treatment is warranted when frequent migraines interfere with daily activities despite treatment in the acute period. Some experts consider onabotulinum toxin A to be the drug of choice.

Patients who often use analgesic drugs (for example, more than 2 times a week), especially for headaches caused by excessive use of drugs, preventive treatment should be combined with measures aimed at stopping the excessive use of analgesics. The choice of drug may be based on concomitant pathology:

• Amitriptyline dosage at night for patients with insomnia
• Beta-blockers - in patients with anxiety or coronary heart disease
• Topiramate, when taking which weight loss develops, for patients who do not want to gain weight
• Monoclonal antibodies (e.g., erenumab, fremanezumab, galcanezumab), when other drugs have been shown to be ineffective
• Hepants can be used for acute attacks (ubrohepant, rimegepant) and for the prevention (atogepant, rimegepant) of migraine

Monoclonal antibodies, used to prevent migraines, block the activation of calcitonin-gene-related peptide (CGRP), which can trigger migraines.

Neuromodulatory therapy may also be effective. Transcutaneous stimulation of the supraorbital nerve with a device applied to the forehead can reduce the frequency of migraines. Transcranial magnetic stimulation, carried out with a device placed in the area of the occipital bone of the skull, is indicated for the treatment of acute attacks and preventive therapy of migraine in adolescents (≥ 12 years) and adults.