Migraine: Causes, Symptoms, and Treatment

Migraine is a primary neurological pain disorder characterized by recurrent attacks of moderate to severe throbbing headache, often accompanied by nausea, photophobia, phonophobia, and impaired performance. Migraine is a leading cause of years lost and disability in people under 50 years of age, according to global epidemiological studies. [1]

The disease progresses in phases: prodromal symptoms occur hours or days before an attack, sometimes an aura with reversible neurological phenomena, followed by a painful phase and a postdrome with fatigue and cognitive "fog." This structure reflects complex neurobiological mechanisms, including cortical spreading depression during aura and activation of the trigeminovascular system. [2]

Migraine is a heterogeneous condition with various subtypes: without aura, with aura, chronic, menstruation-associated, vestibular, hemiplegic, and other rare variants. Subtypes and diagnostic criteria are systematized in the International Classification of Headache Disorders, Third Revision. [3]

The clinical significance of migraine is great not only because of the severity of attacks, but also because of the risk of chronicity, comorbid anxiety and depression, and a moderately increased risk of ischemic stroke in some patients with migraine with aura, especially when smoking and using combined hormonal contraceptives. [4]

Code according to ICD 10 and ICD 11

In the International Classification of Diseases, 10th revision, section G43 includes the main forms of migraine: without aura, with aura, migraine status, complicated form, as well as codes for other clarifications. These codes are used for clinical documentation, statistics, and reimbursement. [5]

In the International Classification of Diseases, 11th revision, category 8A80 covers migraine in general and its subcategories: without aura, with aura, chronic migraine, and other specified and unspecified forms. The International Classification of Diseases, 11th revision, is better aligned with the current International Classification of Headache Disorders, facilitating comparison of clinical and coding approaches. [6]

Table 1. International Classification of Diseases codes for migraine

Classification	Code	Name
ICD 10	G43.0	Migraine without aura
ICD 10	G43.1	Migraine with aura
ICD 10	G43.2	Migraine status
ICD 10	G43.3	Complicated migraine
ICD 10	G43.8 G43.9	Other specified and unspecified forms
ICD 11	8A80.0	Migraine without aura
ICD 11	8A80.1	Migraine with aura
ICD 11	8A80.2	Chronic migraine
ICD 11	8A80.Y 8A80.Z	Other specified and unspecified forms

Epidemiology

Migraine is one of the most common neurological diseases in the world; according to the Global Burden of Disease projects, the prevalence approaches 15% of the population, with women affected approximately 2-3 times more often than men.[7]

The disease most often begins in adolescence and young adulthood, peaking in the 30s and 40s, after which the frequency of attacks decreases in many individuals. Despite this, migraine remains the leading cause of disability among people under 50, underscoring its socioeconomic significance. [8]

Chronic migraine, defined as the presence of headache on at least 15 days per month for 3 months, of which at least 8 days meet the criteria for migraine, is less common than the episodic form but carries a higher risk of disability and comorbidity.[9]

Factors that influence the unfavorable course and progression include inadequately controlled attacks, medication-induced headaches, cutaneous allodynia, obesity, sleep disturbances, and psychoemotional disorders. Timely prevention and correction of modifiable factors reduce the risk of chronicity. [10]

Reasons

Migraine has a polygenic nature, with high heritability and a complex interaction of genetic and environmental factors. Genetic variants influence cortical excitability, ion channel function, neuropeptide regulation, and pain transmission. Familial forms, such as hemiplegic migraine, illustrate the role of monogenic mechanisms, but most cases are polygenic. [11]

Attack triggers vary widely: sleep deprivation or excess, stress and subsequent "release," fluctuations in sex hormones, hunger or dehydration, bright light, strong odors, certain foods, and alcohol. These factors do not "cause" migraines, but they lower the attack threshold in predisposed brains. [12]

A key role is played by calcitonin gene-related peptide and other molecules of the trigeminovascular system, which mediate neurogenic vasodilation and inflammation of the membranes, contributing to pain and hyperalgesia. This is confirmed by the effectiveness of drugs targeting this pathway. [13]

In some patients, the attack is preceded by prodromal signals - yawning, food cravings, mood changes, stiffness of the neck muscles, which reflects the involvement of the hypothalamus and brainstem structures responsible for homeostasis and nociception. [14]

Risk factors

Non-modifiable factors include female gender, reproductive age, and family history. They are associated with a higher likelihood of onset and more severe migraine. [15]

Modifiable factors include obesity, frequent and irrational use of symptomatic analgesics, poor sleep, high stress levels, anxiety-depressive symptoms, and low self-efficacy in managing attacks. Addressing these factors reduces attack frequency and the risk of chronicity. [16]

People with migraine with aura have a moderately increased risk of ischemic stroke, which is exacerbated by smoking and the use of combined hormonal contraceptives. The combined influence of these factors requires an individualized contraceptive strategy. [17]

Medication-induced overuse headache occurs when triptans, combination analgesics, and opioids are used more frequently than the recommended monthly dose, which in itself maintains a high level of pain and chronicity. Prompt training in frequency of use is a preventative measure. [18]

Pathogenesis

The prodrome and postdrome indicate the involvement of hypothalamic-brainstem networks regulating the sleep-wake cycle, feeding behavior, and stress response. This explains the appearance of thirst, yawning, irritability, and cognitive "inertia" around the attack. [19]

The aura is associated with cortical spreading depression, a wave of short-term hyperexcitability followed by suppression of neural activity that correlates with positive and negative visual phenomena.[20]

Pain is generated by activation of the trigeminovascular system and the release of neuropeptides, primarily calcitonin gene-related peptide, substance P, and other mediators, leading to neurogenic inflammation of the dura mater. Central sensitization explains allodynia and the decreased effectiveness of late analgesic administration. [21]

Identification of key links is a feature of modern therapy: drugs that block calcitonin gene-related peptide and its receptor have proven effective in both preventing and stopping attacks, confirming the central role of this pathway. [22]

Symptoms

A typical attack is a unilateral throbbing pain of moderate to severe intensity, worsening with physical activity and accompanied by nausea and/or vomiting, photophobia, and phonophobia. The duration without treatment ranges from 4 to 72 hours. [23]

Auras are reversible focal symptoms, most often visual: flickering, zigzag lines, and scotomas. Sensory, speech, brainstem, and motor phenomena are also possible. Each symptom develops gradually over 5-60 minutes, and the entire aura typically resolves before the onset of pain or at its onset. [24]

Prodromal symptoms include yawning, frequent urination, food cravings, mood swings, and neck stiffness. Postdromal symptoms include fatigue, hypersensitivity to stimuli, and brain fog. [25]

Some patients experience autonomic symptoms—lacrimation, nasal congestion, redness of the eye on the side of the pain, dizziness, and imbalance in vestibular migraine. The severity and range of symptoms vary between attacks and patients. [26]

Classification, forms and stages

The International Classification of Headache Disorders, Third Revision, distinguishes between migraine without aura and migraine with aura, as well as chronic migraine, probable migraine, status migraine, migraineous infarction, and persistent aura without infarction. It also identifies aura subtypes and special forms, including vestibular and hemiplegic.[27]

The staging includes a prodrome, an aura (if present), a pain phase, and a postdrome period. Understanding the stages is important for choosing the right time for therapy: early treatment increases the likelihood of relief and prevents central sensitization. [28]

Chronic migraine is diagnosed when headaches occur on at least 15 days per month for 3 months, of which at least 8 days meet the criteria for migraine or are relieved by specific medications. It requires different preventive measures, including botulinum toxin and antibodies to calcitonin gene-related peptide. [29]

Menstrual-associated migraine occurs in a significant proportion of women of reproductive age; attacks are often predictable and may require short prophylactic regimens around menstruation. Vestibular migraine presents with attacks of dizziness and imbalance, consistent with the Barany Society criteria and the International Classification of Headache Disorders. [30]

Complications and consequences

Drug-induced overuse headache is a common complication of excessive use of triptans, combination analgesics, opioids, and sometimes nonsteroidal anti-inflammatory drugs. This condition maintains a high level of pain and reduces the effectiveness of treatment, therefore requiring weaning off the excessive medications and prevention. [31]

Migraine with aura is associated with a moderately increased risk of ischemic stroke, particularly in women younger than 45 years, smokers, and users of combined hormonal contraceptives, necessitating assessment of vascular risk and selection of contraceptives.[32]

The chronic form sharply reduces the quality of life, increases the risk of anxiety and depression, sleep disturbances and social isolation, which requires a multidisciplinary approach: pharmacoprophylaxis, psychotherapy, lifestyle modification, treatment of comorbid conditions. [33]

Rarely, migraine infarction and persistent aura without infarction occur, which require the exclusion of vascular pathology and management according to the principles of acute neurological conditions, followed by specialized prevention. [34]

When to see a doctor

Seeking medical attention is indicated in the presence of new or changing pain patterns, unusual intensity, the onset of neurological deficits, impaired consciousness, high fever, neck stiffness, in pregnant women, and in people over 50 years of age at the first headache episode. These are "red flags," collectively known as the SNOOP10 criteria. [35]

A scheduled consultation is recommended if the attack frequency is 4 or more per month, there is a significant loss of quality of life, relief therapy is ineffective or intolerable, and medication-induced overuse headache is suspected. Early prevention reduces the risk of chronic headache. [36]

Immediate medical attention is required in the case of a sudden “thunderclap” headache, the first occurrence of the most severe pain in life, persistent neurological symptoms, head trauma, immunodeficiency and oncopathology. [37]

During pregnancy, any new headaches require evaluation to rule out preeclampsia and other secondary causes; treatment strategies during this period have safety considerations. [38]

Diagnostics

The first step is a detailed medical history: onset, duration, and frequency, pain character, associated symptoms, relationship with activity, triggers, medication history, family history, and headache diary. Already at this stage, in most cases, a diagnosis can be made according to the criteria of the International Classification of Headache Disorders, Third Revision. [39]

The second step is a neurological examination assessing cognition, cranial nerves, coordination, and sensation. Routine neuroimaging is not required with a normal examination and typical migraine symptoms. It is indicated for "red flags," atypia, focal deficits, older age of onset, and changes in pain patterns. [40]

The third step is minimal laboratory testing as indicated to rule out secondary causes: signs of inflammation, coagulation disorders, toxic effects, pregnancy. There are no specific "migraine tests"; the diagnostic value of laboratory testing without a clinical basis is low. [41]

The fourth step is to assess the risk of medication-induced headache: days of medication use per month for each group. If thresholds are exceeded, a plan for discontinuing excess medications, replacing treatment strategies, and initiating prophylaxis is discussed. [42]

The fifth step is an analysis of comorbid conditions and chronicity factors: obesity, sleep apnea, depression and anxiety, sleep disorders, stress. This influences the choice of prevention and the expected effectiveness. [43]

Table 2. When neuroimaging is needed for headaches

Situation	Justification
The most severe pain in my life that arose for the first time	Exclusion of subarachnoid hemorrhage and vascular accidents
Focal neurological deficit or altered consciousness	Exclusion of stroke, space-occupying and inflammatory processes
Older age of onset and progressive change in the nature of pain	Exclusion of secondary causes
Immunodeficiency, oncopathology, systemic symptoms	Exclusion of infections and metastases
Atypical aura, prolonged aura, pattern change	Exclusion of migraine infarction and other conditions

Differential diagnosis

Tension headaches are usually bilateral, compressive, mild to moderate in intensity, without nausea, and slightly worsened by activity. Unlike migraine, the typical triad of photophobia, phonophobia, and nausea is absent. [44]

Cluster headaches are brief, intense, unilateral attacks with pronounced autonomic symptoms on the side of pain and motor agitation, which distinguishes it sharply from migraine. Individual attacks last 15-180 minutes with marked periodicity. [45]

Transient ischemic attack with visual symptoms is characterized by a sudden onset, often negative phenomena, maximum severity at the onset and short duration, whereas migraine aura develops gradually and often includes positive phenomena. [46]

Sinusitis, cervicogenic pain, angle-closure glaucoma, and temporal arteritis mimic migraine but have distinctive features and require targeted investigations in the presence of appropriate red flags and clinical clues.[47]

Table 3. Differences between migraine and its frequent “doubles”

State	The nature of pain	Escort	Attack duration	The key to distinction
Migraine	Throbbing, often one-sided	Nausea, photophobia, phonophobia	4-72 hours	Increased with activity, prodrome, aura
Tension headache	Compressive, bilateral	No nausea, mild photophobia and sound phobia	30 minutes to 7 days	Less disruptive to daily life
Cluster headache	Extreme intensity, one-sided	Lacrimation, rhinorrhea, agitation	15-180 minutes	Pronounced autonomic signs
Transient ischemic attack	It doesn't always hurt	Focal deficit	Minutes	Sudden onset, negative symptoms
Sinusitis	Dull, oppressive	Rhinitis, fever	Days	Pain when bending, fever

Treatment

The strategy begins with principles: early administration of pain-relieving medications when pain worsens, tailoring a plan for mild and severe attacks, limiting the frequency of symptomatic medications, taking into account comorbidities and patient preferences, and training in self-management and diary keeping. Early and adequate control reduces the risk of sensitization and chronicity. [48]

For mild to moderate attacks, nonsteroidal anti-inflammatory drugs and acetaminophen are effective, sometimes in combination with antiemetics. The combination of sumatriptan and naproxen is superior to monotherapy in terms of the likelihood of sustained relief and a reduction in daily relapses. Limiting the frequency of administration is necessary to prevent hyper-use headaches. [49]

Migraine-specific medications include triptans, gepants, and ditans. Triptans are highly effective but have vasoconstrictive effects and are contraindicated in certain cardiovascular conditions. Gepants for relief—ubrogepant, rimegepant, and intranasal zavegepant—have demonstrated efficacy without vasoconstrictive effects. Lasmiditan, a ditan, activates serotonin type 1F receptors and is suitable for patients with contraindications to triptans, but may cause sedation, which limits driving on the day of administration. [50]

The approach to vomiting and severe nausea includes metoclopramide or domperidone as indicated, fluid intake, and rest in a quiet, darkened room. Opioids are not recommended due to their low efficacy and high risk of overuse headache; they are reserved for rare, resistant cases with strict monitoring. [51]

Prevention is indicated for seizures with a frequency of at least 4 per month, severe disability, and the ineffectiveness of treatment or contraindications. First-line treatment includes beta-blockers, tricyclic antidepressants, anticonvulsants, and some antihypertensive agents. The choice depends on comorbidities and tolerability profile. [52]

Botulinum toxin type A is effective for chronic migraine using the PREEMPT protocol. It reduces the number of headache days and improves quality of life with a favorable safety profile; the dosage and injection schedule are standardized. [53]

Current preventive treatments include monoclonal antibodies to calcitonin gene-related peptide or its receptor and oral gepants for daily prophylaxis. The 2024 position statement of the American Headache Society recognizes these drugs as first-line options without the requirement for prior failure with traditional agents, reflecting their specific action and high tolerability profile. [54]

Non-pharmacological options are important for reducing the frequency and severity of attacks: cognitive behavioral therapy, relaxation, mindfulness approaches, and biofeedback. Regular physical activity, particularly strength training and vigorous aerobic exercise, has been shown to significantly reduce migraine burden. Weight management in obese individuals further reduces attack frequency. [55]

Non-implantable neuromodulation devices—external trigeminal nerve stimulation, single-pulse transcranial magnetic stimulation, non-invasive vagal stimulation, and external electrical stimulation—may be considered in patients with drug intolerance, in pregnant women, and in those with a strong preference for a non-drug strategy. Efficacy has been demonstrated for some devices in both relief and prevention. [56]

Menstrual-associated migraine may require short-term prophylaxis in the second half of the cycle: long-acting triptans, magnesium, and hormonal modulation methods under supervision. The choice of strategy takes into account contraception and vascular risks. [57]

Migraine status requires infusion protocols in a medical facility with the use of antiemetics, hydration, nonsteroidal anti-inflammatory drugs, intravenous magnesium, sometimes corticosteroids when indicated, and exclusion of secondary causes. Guidelines emphasize individualization and early referral for help. [58]

Table 4. Attack relief: proven options

Class	Examples	Key points
Nonsteroidal anti-inflammatory drugs and acetaminophen	Ibuprofen, naproxen, acetaminophen	Early admission, frequency control per month
Triptans	Sumatriptan, zolmitriptan, rizatriptan, etc.	High efficiency, cardiovascular limitations
Hepants	Ubrogepant, rimegepant, intranasal zavegepant	No vasoconstrictive effects, suitable for those with contraindications to triptans
Ditan	Lasmiditan	Sedation may occur, driving restrictions may apply on the day of the appointment.
Antiemetic drugs	Metoclopramide, domperidone	Reduced nausea, improved absorption

Table 5. Prevention: from traditional to targeted

Group	Examples	Notes and evidence base
Beta-blockers	Propranolol, metoprolol	First line in the absence of contraindications
Antidepressants	Amitriptyline, venlafaxine	Selection based on sleep and mood comorbidity
Anticonvulsants	Topiramate, valproate	Topiramate is effective; valproate is contraindicated during pregnancy and when planning pregnancy.
Antihypertensive drugs	Candesartan	Alternative in case of intolerance to others
Botulinum toxin type A	According to the PREEMPT protocol	Effective for chronic migraine
Antibodies to calcitonin gene-related peptide or its receptor	Erenumab, fremanezumab, galcanezumab, eptinizumab	Recommended as first line in 2024
Oral gepants for prophylaxis	Atogepant, rimegepant	Daily or every other day as indicated

Table 6. Neuromodulation devices

Technology	Scope of application	Comments
External stimulation of the trigeminal nerve	Prevention and relief	Convenient for daily use
Single pulse transcranial magnetic stimulation	Aura and cupping	Portable devices with proven effectiveness in some patients
Non-invasive vagus nerve stimulation	Treatment and prevention	No systemic side effects
Remote electrical stimulation	Docking	Control from your phone, convenient for early start

Table 7. Special groups: pregnancy and lactation

Situation	What is allowed	What to avoid
Pregnancy	Acetaminophen; limited use of nonsteroidal anti-inflammatory drugs in the second trimester; sumatriptan upon approval	Valproate is contraindicated; nonsteroidal anti-inflammatory drugs in the third trimester; opioids
Planning a pregnancy	Maximum non-drug measures, transition to safe regimens	Valproate and potential teratogenic agents
Lactation	Individually, acetaminophen and some triptans are often possible	Long-acting opioids

Prevention

Regular sleep with consistent bedtimes and wake-up times, adequate hydration, regular meals without prolonged fasting, moderate caffeine, stress management, and scheduled exercise reduce the likelihood of attacks. Keeping a diary helps identify individual patterns and points of intervention. [59]

Physical activity is an independent preventative option: strength training and intense aerobic exercise show the greatest reduction in attack frequency; regularity and gradual progression are essential for sustained results. Weight loss in obese individuals further reduces migraine burden. [60]

Behavioral approaches—cognitive behavioral therapy, relaxation, and mindfulness—reduce the incidence and disability, especially when combined with pharmacotherapy. The choice of approach depends on availability and preference; the evidence base is growing, including studies in children and adolescents. [61]

Nutraceuticals can be considered as supplements: magnesium, riboflavin, and coenzyme Q10 have varying degrees of evidence; however, butterbur extract is no longer recommended due to the risk of hepatotoxicity. The decision on use and dosage should be made by a physician, taking into account concomitant conditions. [62]

Table 8. Nutraceuticals: What is important to discuss

Means	Potential benefits	Security considerations
Magnesium	Reduction in the frequency of attacks	Diarrhea at high doses, selection of salt form
Riboflavin	Reduction in migraine days with long-term use	Safe, colors urine
Coenzyme Q10	Possible reduction in frequency	Cost, variability of forms
Butterbur extract	Previously considered	Not recommended due to hepatotoxicity

Forecast

In a significant proportion of patients, the frequency of attacks decreases over time, especially after 40–50 years of age, although some remain chronic, requiring long-term prevention and non-drug strategies. [63]

The prognosis improves with early initiation of adequate relief, limiting the frequency of taking symptomatic medications, starting prophylaxis when indicated, and working with modifiable factors - sleep, weight, stress, comorbidity. [64]

In the migraine with aura group, it is important to control vascular risk factors and avoid combinations that increase the risk of stroke, such as smoking and some forms of hormonal contraception. Personalized contraceptive choice reduces risks. [65]

Modern targeted agents – antibodies to calcitonin gene-related peptide and oral gepants – have expanded the possibilities of prevention and in some patients allow for clinical remission or a significant reduction in migraine days. [66]

Answers to frequently asked questions

Is it true that "strong coffee" triggers migraines in everyone? No. Caffeine affects different people differently: for some, it triggers an attack, while for others, moderate doses help relieve pain. A stable daily intake, without sudden fluctuations and without evening doses, is recommended. [67]

How many times a month can you take painkillers without causing headaches? Safe limits depend on the class: triptans and combination analgesics should be used no more than 9-10 days a month, and nonsteroidal anti-inflammatory drugs (NSAIDs) no more than 14-15 days. Exceeding these limits increases the risk of recurrent headaches. [68]

Is an aura always dangerous for blood vessels? Aura moderately increases the risk of ischemic stroke, especially in women who smoke and use combined hormonal contraceptives. Choosing contraception and quitting smoking reduce the risk. [69]

Is it possible to treat migraines during pregnancy? Yes, but the choice of medications is limited by fetal safety: acetaminophen is the first-line drug; nonsteroidal anti-inflammatory drugs are permitted in a limited manner in the second trimester; sumatriptan is considered by prior agreement. Valproate is contraindicated. [70]

Should targeted prophylaxis be initiated immediately? The decision is individual. In 2024, specialized societies recognized antibodies to calcitonin gene-related peptide and gepants as acceptable first-line prophylaxis, without the need for prior "testing" of traditional agents, taking into account availability and cost. [71]