cortical spreading depression, or spreading depression according to leão, is a burst of neuronal activity followed by a period of inactivity, which is seen in those with migraines with aura. there are a number of explanations for its occurrence, including activation of nmda receptors leading to calcium entering the cell. after the burst of activity, the blood flow to the cerebral cortex in the area affected is decreased for two to six hours. it is believed that when depolarization travels down the underside of the brain, nerves that sense pain in the head and neck are triggered. pain the exact mechanism of the head pain which occurs during a migraine episode is unknown. some evidence supports a primary role for central nervous system structures (such as the brainstem and diencephalon), while other data support the role of peripheral activation (such as via the sensory nerves that surround blood vessels of the head and neck). the potential candidate vessels include dural arteries, pial arteries and extracranial arteries such as those of the scalp. the role of vasodilatation of the extracranial arteries, in particular, is believed to be significant. neuromodulators adenosine, a neuromodulator, may be involved. released after the progressive cleavage of adenosine triphosphate (atp), adenosine acts on adenosine receptors to put the body and brain in a low activity state by dilating blood vessels and slowing the heart rate, such as before and during the early stages of sleep. adenosine levels have been found to be high during migraine attacks. caffeine's role as an inhibitor of adenosine may explain its effect in reducing migraine. low levels of the neurotransmitter serotonin, also known as 5-hydroxytryptamine (5-ht), are also believed to be involved. calcitonin gene-related peptides (cgrps) have been found to play a role in the pathogenesis of the pain associated with migraine, as levels of it become elevated during an attack. diagnosis the diagnosis of a migraine is based on signs and symptoms. neuroimaging tests are not necessary to diagnose migraine, but may be used to find other causes of headaches in those whose examination and history do not confirm a migraine diagnosis. it is believed that a substantial number of people with the condition remain undiagnosed. the diagnosis of migraine without aura, according to the international headache society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria": five or more attacks—for migraine with aura, two attacks are sufficient for diagnosis. four hours to three days in duration two or more of the following: unilateral (affecting one side of the head) pulsating moderate or severe pain intensity worsened by or causing avoidance of routine physical activity one or more of the following: nausea and/or vomiting sensitivity to both light (photophobia) and sound (phonophobia) if someone experiences two of the following: photophobia, nausea, or inability to work or study for a day, the diagnosis is more likely. in those with four out of five of the following: pulsating headache, duration of 4–72 hours, pain on one side of the head, nausea, or symptoms that interfere with the person's life, the probability that this is a migraine attack is 92%. in those with fewer than three of these symptoms, the probability is 17%. classification main article: ichd classification and diagnosis of migraine migraine was first comprehensively classified in 1988. the international headache society updated their classification of headaches in 2004. a third version was published in 2018. according to this classification, migraine is a primary headache disorder along with tension-type headaches and cluster headaches, among others. migraine is divided into seven subclasses (some of which include further subdivisions): migraine without aura, or "common migraine", involves migraine headaches that are not accompanied by aura. migraine with aura, or "classic migraine", usually involves migraine headaches accompanied by aura. less commonly, aura can occur without a headache, or with a nonmigraine headache. two other varieties are familial hemiplegic migraine and sporadic hemiplegic migraine, in which a person has migraine with aura and with accompanying motor weakness. if a close relative has had the same condition, it is called "familial", otherwise it is called "sporadic". another variety is basilar-type migraine, where a headache and aura are accompanied by difficulty speaking, world spinning, ringing in ears, or a number of other brainstem-related symptoms, but not motor weakness. this type was initially believed to be due to spasms of the basilar artery, the artery that supplies the brainstem. now that this mechanism is not believed to be primary, the symptomatic term migraine with brainstem aura (mba) is preferred. childhood periodic syndromes that are commonly precursors of migraine include cyclical vomiting (occasional intense periods of vomiting), abdominal migraine (abdominal pain, usually accompanied by nausea), and benign paroxysmal vertigo of childhood (occasional attacks of vertigo). retinal migraine involves migraine headaches accompanied by visual disturbances or even temporary blindness in one eye. complications of migraine describe migraine headaches and/or auras that are unusually long or unusually frequent, or associated with a seizure or brain lesion. probable migraine describes conditions that have some characteristics of migraines, but where there is not enough evidence to diagnose it as a migraine with certainty (in the presence of concurrent medication overuse). chronic migraine is a complication of migraines, and is a headache that fulfills diagnostic criteria for migraine headache and occurs for a greater time interval. specifically, greater or equal to 15 days/month for longer than 3 months. abdominal migraine the diagnosis of abdominal migraine is controversial. some evidence indicates that recurrent episodes of abdominal pain in the absence of a headache may be a type of migraine or are at least a precursor to migraines. these episodes of pain may or may not follow a migraine-like prodrome and typically last minutes to hours. they often occur in those with either a personal or family history of typical migraine. other syndromes that are believed to be precursors include cyclical vomiting syndrome and benign paroxysmal vertigo of childhood. differential diagnosis other conditions that can cause similar symptoms to a migraine headache include temporal arteritis, cluster headaches, acute glaucoma, meningitis and subarachnoid hemorrhage. temporal arteritis typically occurs in people over 50 years old and presents with tenderness over the temple, cluster headache presents with one-sided nose stuffiness, tears and severe pain around the orbits, acute glaucoma is associated with vision problems, meningitis with fevers, and subarachnoid hemorrhage with a very fast onset. tension headaches typically occur on both sides, are not pounding, and are less disabling. those with stable headaches that meet criteria for migraines should not receive neuroimaging to look for other intracranial disease. this requires that other concerning findings such as papilledema (swelling of the optic disc) are not present. people with migraines are not at an increased risk of having another cause for severe headaches. prevention main article: prevention of migraines preventive treatments of migraine include medications, nutritional supplements, lifestyle alterations, and surgery. prevention is recommended in those who have headaches more than two days a week, cannot tolerate the medications used to treat acute attacks, or those with severe attacks that are not easily controlled. recommended lifestyle changes include stopping tobacco use and reducing behaviors that interfere with sleep. the goal is to reduce the frequency, painfulness, and duration of migraine episodes, and to increase the effectiveness of abortive therapy. another reason for prevention is to avoid medication overuse headache. this is a common problem and can result in chronic daily headache. medication preventive migraine medications are considered effective if they reduce the frequency or severity of the migraine attacks by at least 50%. due to few medications being approved specifically for the preventative treatment of migraine headaches; many medications such as beta-blockers, anticonvulsive agents such as topiramate or sodium valproate, antidepressants such as amitriptyline and calcium channel blockers such as flunarizine are used off label for the preventative treatment of migraine headaches. guidelines are fairly consistent in rating the anticonvulsants topiramate and divalproex/sodium valproate, and the beta blockers propranolol and metoprolol as having the highest level of evidence for first-line use for migraine prophylaxis in adults. propranolol and topiramate have the best evidence in children; however, evidence only supports short-term benefit as of 2020. the beta blocker timolol is also effective for migraine prevention and in reducing migraine attack frequency and severity. while beta blockers are often used for first-line treatment, other antihypertensives also have a proven efficiency in migraine prevention, namely the calcium channel blocker verapamil and the angiotensin receptor blocker candesartan. tentative evidence also supports the use of magnesium supplementation. increasing dietary intake may be better. recommendations regarding effectiveness varied for the anticonvulsants gabapentin and pregabalin. frovatriptan is effective for prevention of menstrual migraine. the antidepressants amitriptyline and venlafaxine are probably also effective. angiotensin inhibition by either an angiotensin-converting enzyme inhibitor or angiotensin ii receptor antagonist may reduce attacks. medications in the anti-calcitonin gene-related peptide, including eptinezumab, erenumab, fremanezumab, and galcanezumab, appear to decrease the frequency of migraines by one to two per month. they are, however, expensive: a year of erenumab costs $6,900 as of 2019. alternative therapies acupuncture has a small effect in reducing migraine frequency, compared to sham acupuncture, a practice where needles are placed randomly or do not penetrate the skin. physiotherapy, massage and relaxation, and chiropractic manipulation might be as effective as propranolol or topiramate in the prevention of migraine headaches; however, the research had some problems with methodology. another review, however, found evidence to support spinal manipulation to be poor and insufficient to support its use. tentative evidence supports the use of stress reduction techniques such as cognitive behavioral therapy, biofeedback, and relaxation techniques. regular physical exercise may decrease the frequency. numerous psychological approaches have been developed that are aimed at preventing or reducing the frequency of migraine in adults including educational approaches, relaxation techniques, assistance in developing coping strategies, strategies to change the way one thinks of a migraine attack, and strategies to reduce symptoms. other strategies include: progressive muscle relaxation, biofeedback, behavioral training, acceptance and commitment therapy, and mindfulness-based interventions. the medical evidence supporting the effectiveness of these types of psychological approaches is very limited. among alternative medicines, butterbur has the best evidence for its use. however, unprocessed butterbur contains chemicals called pyrrolizidine alkaloids (pas) which can cause liver damage, however there are versions that are pa free. in addition, butterbur may cause allergic reactions in people who are sensitive to plants such as ragweed. there is tentative evidence that coenzyme q10 reduces migraine frequency. feverfew has traditionally been used as a treatment for fever, headache and migraine, women's conditions such as difficulties in labour and regulation of menstruation, relief of stomach ache, toothache and insect bites. during the last decades, it has mainly been used for headache and as a preventive treatment for migraine. the plant parts used for medicinal use are the dried leaves or the dried aerial parts. several historical data supports feverfew's traditional medicinal uses. in addition, several clinical studies have been performed assessing the efficacy and safety of feverfew monotherapy in the prevention of migraine. the majority of the clinical trials favoured feverfew over placebo. the data also suggest that feverfew is associated with only mild and transient adverse effects. the frequency of migraine was positively affected after treatment with feverfew. reduction of migraine severity was also reported after intake of feverfew and incidence of nausea and vomiting decreased significantly. no effect of feverfew was reported in one study. there is tentative evidence for melatonin as an add-on therapy for prevention and treatment of migraine. the data on melatonin are mixed and certain studies have had negative results. the reasons for the mixed findings are unclear but may stem from differences in study design and dosage. melatonin's possible mechanisms of action in migraine are not completely clear, but may include improved sleep, direct action on melatonin receptors in the brain, and anti-inflammatory properties. devices and surgery medical devices, such as biofeedback and neurostimulators, have some advantages in migraine prevention, mainly when common anti-migraine medications are contraindicated or in case of medication overuse. biofeedback helps people be conscious of some physiological parameters so as to control them and try to relax and may be efficient for migraine treatment. neurostimulation uses noninvasive or implantable neurostimulators similar to pacemakers for the treatment of intractable chronic migraine with encouraging results for severe cases. a transcutaneous