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Marja-LiisaSumelahti

Migraine

Essentials

  • Effective drug treatment of a migraine attack should be started when the pain is mild.
  • Paracetamol or NSAIDs in sufficient doses are suitable for the treatment of mild migraine attacks.
  • In severe attacks, triptans are the primary choice.
  • In prolonged and severe attacks, a triptan can be combined with an NSAID, and the combination can be taken again within the next 24 hours.
  • The antiemetic metoclopramide should be given in addition to analgesics.
  • Prophylactic medication should be started if the frequency or severity of attacks affects the patient's functional ability.
  • As it has been shown that opioids do not improve the results of migraine treatment and involve a risk of drug-induced headache, they should not be used.

Definition and epidemiology

  • Migraine is a paroxysmal neurovascular disease. Of several mediators, the protein known as calcitonin gene-related peptide (CGRP) plays a role in the development of migraine pain.
  • The prevalence of migraine in the adult population is about 10%, in men 5% and in women 15%.
  • According to the international ICHD-3 classification, migraine attacks are classified into attacks without aura (85%) and attacks with prodromal symptoms, or aura (15%). The latter consist of typical attacks with visual aura and rarer types of migraine with aura, such as migraine with brainstem aura, hemiplegic migraine and retinal migraine.
    • A visual aura is typically a brief positive visual symptom preceding pain.
    • Rarer aura symptoms are brainstem symptoms, such as vertigo, numbness, speech or swallowing disturbances or symptoms of motor paralysis.
  • Factors precipitating migraine attacks include changes in the amount of stress, disturbance of the sleep-wake rhythm, hypoglycaemia and, in women, lowered oestrogen levels during menstruation or during breaks in taking combined oral contraceptives.

Symptoms

  • A migraine attack is divided into premonitory stage, aura, headache stage and postdrome stage.
  • In adults, the duration of a migraine attack is 4-72 hours.
  • During a few days before the attack, and after the attack, there may be changed alertness.
  • Typical symptoms include yawning, a craving for sweets, tiredness, and irritability.
  • The headache stage may be preceded by aura, or prodromal symptoms, lasting for 5-60 minutes.
    • A common visual aura is an enlarging, scintillating scotoma with bright margins, a grey or bright area with serrated edges.
    • A unilateral sensory disturbance, difficulty finding words or motor paralysis may also represent an aura.
  • A migraine aura can occur without a subsequent headache.
  • Migraine headache is a pulsating, often unilateral severe or moderate headache getting worse on exertion. In addition, there may be nausea or vomiting as well as general sensory sensitivity (to light, sounds, smells).
  • The attack is associated with disturbances of the autonomic nervous system. During the attack, the patient prefers to lie down in a dark, cool and silent room.

Diagnosis

  • Diagnosis is based on patient history. The neurological status is normal between attacks.
  • The diagnostic criteria are defined in the ICHD-3 (International Classification of Headache Disorders).
  • Neuroimaging is not warranted in adult patients with typical migraine and normal neurological status Does This Patient with Headache Need Neuroimaging?.

Diagnostic criteria

Diagnostic criteria of migraine with typical aura

Migraine with typical aura - Modified ICHD-3 criteria (1.2.1)
AAt least two attacks fulfilling criteria B and C
BAura consisting of visual, sensory and/or speech/language symptoms, each fully reversible, but no motor, brainstem or retinal symptoms
CAt least two of the following four characteristics:
1at least one aura symptom spreads gradually over HASH(0x2fcfe80) 5 min, and/or two or more symptoms occur in succession
2each individual aura symptom lasts at least 5 but less than 60 minutes
3at least one aura symptom is unilateral
4the aura is accompanied, or followed within 60 min, by headache
DNot better accounted for by another ICHD-3 diagnosis, and transient ischaemic attack (TIA) has been excludedhttp://ihs-headache.org/en/resources/guidelines/.

Differential diagnosis

Migraine headache

  • In subarachnoid haemorrhage, the pain has an explosive onset, and it is often associated with a decreased level of consciousness Intracranial Aneurysm and Subarachnoid Haemorrhage (Sah).
  • In meningitis, there is neck stiffness, fever, a decreased level of consciousness and confusion in addition to headache Meningitis in Adults.
  • Cluster headache causes brief, intense pain lasting 15-180 minutes in the region of one eye and is associated with lacrimation Cluster Headache (Horton's Syndrome).
  • Tension headache typically consists of only headache with no additional symptoms, squeezing bilateral pain, no prodromal symptoms, nausea or sensory sensitivity; exercise improves the condition Tension Headache.

Migraine aura

  • Temporal lobe epilepsy seizure
  • In an occipital lobe epilepsy seizure the visual disturbance is more colourful, more “electric” and of a shorter duration than in migraine.
  • The onset of a TIA attack is sudden (in a vertebrobasilar TIA, there is a dark visual field defect, no bright visual sensations, no slow expansion, usually no headache) Transient Ischaemic Attack (Tia).
  • In acute glaucoma, there is severe pain in the eye, which may feel hard when palpated Glaucoma.

Treatment of migraine attack Hyperbaric Oxygen Therapy for Migraine, Parenteral Dexamethasone for Acute Severe Migraine Headache

  • Rest in a calm, quiet, dark environment
  • As the headache stage of a migraine attack begins, an analgesic should already be taken for mild pain, either paracetamol, an NSAID or a triptan (tablet, nasal spray or subcutaneous injection). Triptans can be combined with other analgesics.
  • Paracetamol or an NSAID may be taken already during the aura stage, but triptans, however, should not be taken at that stage yet.
  • A subcutaneously injected triptan is rapidly absorbed and effective even in severe pain. Tablets usually start taking effect within one hour. In prolonged attacks, repeated doses are necessary. Two doses of triptans can be taken within 24 hours.
  • The contraindications for triptans must be observed.
  • Combining 10 mg/day metoclopramide with other drugs used to treat migraine attacks improves their absorption.

Paracetamol and NSAIDs

Triptans

Other drugs

  • Diazepam 2-10 mg p.o./rectally
  • Opioids are not used for the treatment of migraine. Their efficacy is not superior to that of NSAIDs, and they are associated with a risk of drug dependence and analgesic rebound headache.

Medication during pregnancy and lactation

  • Paracetamol can be used throughout pregnancy. Ibuprofen and naproxen can be used in early pregnancy.
  • Triptansare contraindicated during pregnancy and lactation. Occasional use of sumatriptan (less than 4 times) during pregnancy is probably not harmful. Sumatriptan is known to be excreted in breast milk in small amounts; conventional doses should not cause any harm to the infant.

Menstrual migraine

  • Menstrual migraine is a type of migraine without aura that begins between 2 days before or 2 days after the first day of bleeding.
  • The beginning of the attack is associated with a rapid decline in oestrogen levels.
  • Menstrual migraine may be prolonged and intense.
  • If menstrual migraine occurs regularly, the following can be used prophylactically:
    • Naproxen 500 mg twice daily starting 2 days before the menstrual period and continuing until the end of period (at maximum for 7 days).
    • Triptans starting 1-2 days before the period and continuing for 5-7 days, provided that the menstrual cycle and associated migraine are very regular. Drugs for this purpose include:

Treatment of an acute prolonged migraine attack

  • Status migrainosus is a migraine attack with severe symptoms continuing for several days.
  • Treatment should be started without delay on the emergency ward if a patient reports his/her typical migraine symptoms and no secondary causes are suspected.
  • Subcutaneously injected triptans act rapidly.
  • Analgesics and antiemetics should be given parenterally.
  • 500 mg of hydrocortisone and 200 mg of indomethacin mixed with 1 000 ml of sodium chloride 0.9% and glucose 5% solution (NaCl 0.9/G5) can be given intravenously over 6-8 hours.
  • On discharge, the patient should be instructed to contact outpatient care to revise his/her migraine treatment plan.

Preventive therapy Biofeedback for Migraine in Adults, Spinal Manipulation Therapy for Migraine Headache, Ssris and Snris for Preventing Tension-Type Headaches and Migraine

  • Maintaining a steady sleep-wake rhythm and taking meals regularly, avoiding individual precipitating factors.
  • Consideration of the patient's lifestyle and work-related matters: are there factors in the current life situation or at the workplace that may sustain the migraine and is it possible to invervene?
  • Regular physical exercise reduces the incidence of migraine attacks.
  • Preventive medication may be considered if there are four or more attacks in a month.
  • Initially, tablet medication should be tried. Treatment is usually continued for 3-6 months, after which the need for further medication should be considered.
  • Prophylactic tablets reduce the frequency of attacks and severity of pain by 30-50%, at best.
  • Prophylactic medication should be continued as indicated. Often a few months is sufficient, sometimes medication is required for years. The situation of a patient on preventive medication should be regularly monitored both clinically and with a headache diary.
  • Sometimes different preventive drugs have to be combined in order to achieve the desired effect.
  • Beta blockers
    • Propranolol 20-40 mg × 2 or 3 times a day, 160 mg once a day
    • Metoprolol 47.5-200 mg/day
    • Contraindications: asthma, slow heart rate, low blood pressure
  • Candesartan 16 mg once a day Sartans in Migraine Prophylaxis
  • Amitriptyline 10-25 mg/day or nortriptyline 25-50 mg/day, especially if the migraine is associated with tension headache or a tendency to depression
  • Topiramate, starting very carefully with 15-25 mg once daily, increasing the dose with caution to no more than 50 mg twice daily Topiramate for the Prophylaxis of Episodic Migraine in Adults (must not be used during pregnancy)
  • Valproic acidValproate for the Prophylaxis of Episodic Migraine in Adults 300-500 mg × 2 or 3 times a day (see also follow-up of the treatment of epilepsy Treatment of Epilepsy in Adults; must not be used during pregnancy). Is not used for migraine prophylaxis in women of fertile age.
  • Gabapentin has not been shown to be effective in migraine prevention Gabapentin or Pregabalin for the Prophylaxis of Episodic Migraine in Adults. There are no studies on pregabalin in migraine.
  • Botulinum toxin type A has been shown to be effective in the prevention of chronic migraine, only Botulinum Toxins for the Prevention of Migraine in Adults.
  • Among new prophylactic treatments, of the calcitonin gene-related peptide (CGRP) monoclonal antibodies, the subcutaneous erenumab (Aimovig® ), fremanezumab (Ajovy® ) and galcanezumab (Emgality® ) can be used. Check local reimbursement conditions and policies.
  • Botulinum toxin is beneficial in the prevention of chronic migraine. Botulinum Toxins for the Prevention of Migraine in Adults
  • Non-pharmacological forms of prophylaxis

Intervention in chronic daily headache

  • Chronic migraine or chronic daily headache can be diagnosed if there have been 15 or more headache days per month for 3 months.
  • This is frequently a combination of chronic migraine, tension headache and medication overuse.
  • If drug-induced headache is identified, it is necessary to reduce any overuse of migraine medication or discontinue or wean the patient off medication. At the same time, starting migraine prophylaxis is recommended.
  • When analgesics are tapered off over 1-3 weeks, sickness absence may be necessary during the first few days.
  • When planning further treatment, non-pharmacological and pharmacological prophylaxis of various types of headaches should be considered. The patient should be instructed to document the use of headache drugs and rescue medication.

Prognosis Risk of Ischaemic Stroke in People with Migraine with Aura

  • Migraine often starts at school age.
  • If migraine attacks without aura continue to occur in adulthood, in women the frequency decreases during pregnancy and the attacks often cease completely after menopause.
  • Migraine with aura may become more intensive during pregnancy and in patients taking menopausal oestrogen replacement therapy.
  • Migraine with aura is associated with a risk of cerebral infarction which is increased by the use of combination oral contraceptives and smoking Smoking Cessation.

    References

    • Bird S, Derry S, Moore RA. Zolmitriptan for acute migraine attacks in adults. Cochrane Database Syst Rev 2014;(5):CD008616. [PubMed]
    • Law S, Derry S, Moore RA. Sumatriptan plus naproxen for the treatment of acute migraine attacks in adults. Cochrane Database Syst Rev 2016;4():CD008541. [PubMed]
    • Linde M, Mulleners WM, Chronicle EP et al. Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013;(6):CD010609. [PubMed]
    • Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(4):CD008041. [PubMed]
    • Rabbie R, Derry S, Moore RA. Ibuprofen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(4):CD008039. [PubMed]
    • Law S, Derry S, Moore RA. Naproxen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(10):CD009455. [PubMed]
    • Derry S, Moore RA. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;(4):CD008040. [PubMed]
    • Linde M, Mulleners WM, Chronicle EP et al. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013;(6):CD010610. [PubMed]
    • Derry CJ, Derry S, Moore RA. Sumatriptan (oral route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev 2012;(2):CD008615. [PubMed]