Migraine

Migraines are a common primary headache disorder and can present variably. Typically they consist of debilitating headaches, accompanied by an aura in one-third of patients.

Epidemiology

Migraine is a very common condition, with a 1-year prevalence of 12% ⁸. It is most prevalent in early-middle adulthood, although it can manifest at any age ⁸.

Clinical presentation

Migraines have an extremely varied presentation. As a result, many types have been described ⁷:

• migraine with aura (most common type)

• migraine without aura

• aura without headache

• vestibular migraine

• migraine with brainstem aura (basilar-type migraine)

• retinal migraine

• hemiplegic migraine (and familial hemiplegic migraine)

• migraine with unilateral motor symptoms

• menstrual migraine

• abdominal migraine

In migraine with aura, there is a typical sequence of symptoms in four phases that any given patient will experience ^7,8.

• premonitory symptoms ^7,8

  • occur hours to days prior to the headache

  • symptoms are often subtle, such as increased yawning, emotional lability, food cravings, neck stiffness, bowel changes, etc.

• aura ^7,8

  • occur just prior to headache

  • if a visual aura, a variety of positive (e.g. teichopsia) or negative (e.g. visual field loss) phenomena may manifest

• headache ^7,8

  • typically unilateral in the frontotemporal region, but can be more expansive

  • has a throbbing character

  • often associated nausea, vomiting, photophobia, phonophobia, osmophobia, etc.

  • often worsened with physical activity

  • usually lasts 4-72 hours in duration

• postdrome ^7,8

  • occurs after the headache

  • symptoms are often subtle, including exhaustion, poor concentration, etc.

These symptoms or 'attacks' can occur in two patterns ^7,8:

• episodic: <15 migraine days per month, known as 'episodic migraine'

• chronic: ≥15 migraine days per month, known as 'chronic migraine' (previously 'transformed migraine')

Complications

• status migrainosus: migraine attack lasting >72 hours

• persistent aura without infarction

• migrainous vasospasm

• migrainous infarction

• migraine aura-triggered seizures

Pathology

The exact aetiopathogenesis of migraine is yet to be fully elucidated, but is likely highly complex ⁸. It is hypothesized that cortical spreading depression and subsequent activation of the trigeminovascular system, leading to release of neuropeptides such as calcitonin gene-related peptide (CGRP) ⁸.

Genetics

Migraine may have polygenic risk factors, but there are rare instances of monogenic migraine, such as familial hemiplegic migraine due to mutations in the CACNA1A, ATP1A2 or SCNA1 genes ^8,12.

Additionally, albeit very rarely, migraine can be part of other monogenic syndromes, such as ¹²:

• cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

• COL4A1 brain small-vessel disease

• mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)

• hereditary hemorrhagic telangiectasia (HHT)

• retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)

• CACNA1A-related disorders

  • episodic ataxia type 2 (EA2)

  • spinocerebellar ataxia type 6 (SCA6)

• retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome

Radiographic features

MRI

In the vast majority of cases, MRI is essentially normal. In up to 40% of patients with migraine ¹³ there may be non-specific T2 hyperintensities in the white matter of the centrum semiovale, not dissimilar to small vessel deep white matter ischemic change. Additionally, there may be increased T2/FLAIR signal in the cortex overlying white matter abnormalities, in the brainstem, and very rarely reversible signal abnormalities in the convexal subarachnoid spaces ^1,13. In assessing white matter hyperintensities, it is important to consider rare monogenic syndromes (as aforementioned, e.g. CADASIL) in which migraine can be an early clinical manifestation ¹³.

In hemiplegic migraines, venous dilatation may be seen, best appreciated on on SWI MIP images contralateral to the hemiparesis ³. Changes in cerebral perfusion have also been described ³. See the main article on hemiplegic migraines for a detailed discussion.

Treatment and prognosis

Management can be broadly dichotomised into preventative and abortive strategies.

In regards to preventative strategies:

• lifestyle: good sleep hygiene, regular aerobic exercise, having routine meal schedules, having adequate hydration, utilizing relaxation techniques or mindfulness, etc. ⁹

• pharmacotherapy: generally indicated if having >4 migraines per month ⁸

  • oral therapy ⁸

    • antidepressants: amitriptyline, nortriptyline, etc.

    • antihypertensives: propranolol, verapamil, candesartan, etc.

    • antiseizure medications: topiramate, sodium valproate, etc.

    • small molecule CGRP receptor antagonists: rimegepant, ubrogebant, telcagepant, atogepant, zavegepant, etc.

    • others: pizotifen, flunarizine, etc.

  • injectable therapy ⁸

    • CGRP antagonists: galcanezumab, fremanezumab, eptinezumab, erenumab

    • botulinum toxin A injections

    • greater occipital nerve blocks and other cranial nerve blocks

• neuromodulation therapy: external transcutaneous trigeminal nerve stimulation (eTNS), external transcutaneous supraorbital nerve stimulation, single-pulse transcranial magnetic stimulation (sTMS), non-invasive vagal nerve stimulation (nVNS) ¹¹

In regards to abortive strategies ^8,10:

• simple analgesia: acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), soluble aspirin, etc.

• antiemetics: metoclopramide, ondansetron, etc.

• triptans: sumatriptan, naratriptan, zolmitriptan, rizatriptan, eletriptan, etc.

• gepants (as above)

• ditans: lasmiditan, etc.

• advanced therapy for refractory acute pain including status migrainosus: often requiring inpatient hospital admission

  • intermittent intravenous therapies: fluids, dopamine antagonists (e.g. chlorpromazine), corticosteroids, sodium valproate, magnesium sulfate

  • continuous intravenous infusions: lignocaine, ketamine, dihydroergotamine

  • greater occipital nerve blocks and other cranial nerve blocks

  • neuromodulation therapies (as above)

Differential diagnosis

For MRI appearances consider:

• chronic small vessel deep white matter ischemic change

• demyelination (e.g. multiple sclerosis)

• cerebral vasculitis

• stroke