MANAGING MIGRAINES & RED FLAGS FOR SECONDARY HEADACHES
Abstract: This article will discuss migraines, medication overuse and red flags for important secondary headache disorders.
Introduction
There are many causes of headache which have been described in the medical literature and classified in The International Classification of Headache Disorders published by the International Headache Society. For practical clinical purposes, all headaches can be classified as one of the primary headache syndromes or as headaches secondary to an underlying disease process or medical condition. This discussion will focus on one the common primary headache syndromes migraines, as well as touch upon medication overuse headaches. Red flags for important secondary headache disorders will be highlighted.
Epidemiology
Migraines are common, affecting approximately 5% of males and 15% of females in population surveys around the world. Migraines may begin in childhood or early adulthood, reaching peak prevalence in middle-aged women. Migraines rarely occur for the first time after the age of 50 years.
Aetiology
The pathophysiology of migraine is not well understood. In migraines it is believed that the brain is hyper-reactive to triggers such as stress, leading to the generation of a wave of cortical excitation. This is turn activates the trigeminovascular system, causing release of neurotransmitters, vasodilatation and neurogenic inflammation. Nociceptive impulses travel via the trigeminal nerve to the brainstem pain centres, producing headaches. At least some forms of migraines may be genetically determined (eg. familial hemiplegic migraine).
Clinical Features & Differential Diagnosis
Migraines have been described as sick headaches, comprising episodic headaches often unilateral, associated variably with nausea, vomiting, light and noise sensitivity, and dizziness. Often there may be a prodrome in the hours or days preceding a headache, though not always apparent, perhaps comprising fatigue, nausea, depression or food cravings. One in eight migraineurs experiences auras, usually visual (eg. flashes of light, zigzag lines, visual blurring) or somatosensory (eg. numbness, tingling in the face or limbs). Motor phenomena such as hemiplegia are rare.
Prominent negative visual symptoms (ie. loss or obscuration) should raise an index of suspicion of mimics such as amaurosis fugax (transient monocular blindness from carotid atherosclerosis) or optic nerve ischaemia from giant cell arteritis. Transient sensory or motor deficits, especially when auras occur without headaches (aura without headache), should raise the possibility of transient ischaemic attack, stroke or seizures. These red flags should be heeded in patients who are atypical in presentation (eg. older patients with cardiovascular or epilepsy risk factors), especially if they do not have a past history of recurring headaches with similar accompanying neurological phenomena. Such patients may require further evaluation, including specialist referral for tertiary evaluation.
Headaches may last hours or days, and the mean frequency in population studies is about once a month. Migraine triggers include psychological, hormonal, environmental and dietary factors. Common factors include stress (often release from stress in the weekends) and sleep (often too little sleep, or sometimes oversleeping). Some describe an association with menses (menstrual migraine), or changes in pregnancy (eg. may improve in the second and third trimesters) and menopause (eg. worsening during the perimenopausal period). Environmental factors such as cigarette smoke and strong perfume scents can trigger an attack. Certain foods, alcohol, caffeine withdrawal and missing meals can all set off a migraine attack.
Migraines which conform to the International Headache Society criteria for migraine diagnosis and which occur regularly should be straightforward, eg. unilateral, throbbing headaches associated with nausea/vomiting, photophobia and/or sonophobia, perhaps worsened by physical activity, with or without auras.
A red flag for secondary headaches is the migraine patient presenting with the worst headache ever, usually presenting to the A&E department. Only about 1% of patients presenting to the emergency room will turn out to have subarachnoid haemorrhage (SAH), but the chances of SAH rise to 12% of patients who describe the worst headache ever. Clues to SAH include an abrupt onset (thunderclap) headache which spreads through the neck to the interscapular region, neck stiffness, altered consciousness and neurological deficits. Neuroimaging should be considered in every patient describing atypical headaches which do not conform to their usual headache pattern, which are progressive, unresponsive to the usual medications, unusually severe, related to head injury or which are associated with neurological deficits. Besides intracranial haemorrhage, transient ischaemic attack/stroke, seizures and giant cell arteritis, other important diagnostic considerations in patients presenting with severe and acute headaches are hypertension, meningitis, raised intracranial pressure (eg. brain tumour, pseudotumour cerebri) and local ocular conditions like glaucoma. All such patients should have vital signs routinely checked (ie. including temperature, blood pressure) and a thorough neurological examination for signs of meningism (eg. neck stiffness), papilloedema and focal deficits. Signs of raised intracranial pressure include headache, nausea, vomiting, false localizing 6th cranial nerve palsy, altered consciousness, papilloedema, elevated blood pressure and bradycardia. Neurological or ophthalmology consultation may be required in complex cases.
Another important consideration is medication overuse headaches, which should be considered in patients who have very frequent headaches and take analgesics, ergots or triptans very frequently. Most forms of acute headache medication used more than 2 days a week for longer than a few weeks can lead to medication-overuse headache. Headaches may develop or worsen during medication overuse, and should resolve after discontinuation of the overused medication.
Investigations
Common migraines can often be diagnosed on clinical grounds. In older patients presenting with new headaches after the age of 50 years, especially those with a history of temporal headaches and visual symptoms (eg, transient visual blurring, diplopia, eye pain, sudden loss of vision), giant cell arteritis should be excluded. ESR elevation (moderate to >100 mm/h) is common and is rarely (~ 3%) normal. Other acute phase reactants like C-reactive protein (CRP) may also be elevated. The ESR can be followed serially in monitoring for treatment response.
Neuroimaging is indicated when intracranial haemorrhage, ischaemic stroke or space-occupying mass lesions are suspected. CT scans are useful in the detection of fresh blood and skull fractures. MRI is the preferred modality of imaging for acute stroke and for more detailed delineation of the brain parenchyma and mass lesions in the brain, particularly in the posterior fossa which is not well visualized on routine CT scanning of the brain. Contrast enhancement is indicated to better outline infection and neoplasm, if not contraindicated. Lumbar puncture is helpful if not contraindicated (eg. if there is a focal mass lesion with mass effect) to evaluate suspected CNS infection or malignancy and to document opening cerebrospinal (CSF) fluid pressures. Both low and high CSF pressures can cause headaches.
Treatment
Patients should be taught to avoid any identifiable triggers and drug overuse. Mild acute attacks of migraine can be treated with a range of medications including simple analgesics like paracetamol with or without caffeine, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) (eg. Naproxen sodium, ibuprofen) and COX-2 inhibitors. Milder medications should be used for mild attacks, and in general the patient should be told that the medications work better if taken early in an attack. More severe attacks will likely require prescription drugs such as NSAIDs, aspirin, analgesic combinations containing codeine and probably the best, 5HT1 receptor agonists or triptans (eg. sumatriptan, zolmitriptan etc).
The triptans act on cranial blood vessel 5HT1B receptors causing vasoconstriction. They also act on 5HT1D/F receptors to inhibit vasodilation and inflammation, and reduce central transmission of pain. About 65% of migraines will improve within 2 hours of taking a triptan, which should also be taken as early as possible for optimal response. Nasal spray and injection formulations are available for patients with severe nausea and vomiting. Adverse effects include numbness, tingling, flushing and malaise. Chest tightness occur in about 3% of patients for reasons which are unclear, but may in some instances be due to coronary vasoconstriction. As such coronary artery disease is an absolute contraindication to all of the triptans. The ergot derivatives act on the same receptors as triptans, causing more generalized vasoconstriction. They are a less costly and reasonably effective alternative to the triptans. The same contraindications apply to ergots as for triptans.
In extremely severe migraines, secondary headaches such as due to SAH should be considered. Parenteral therapy is often required for severe migraines, including NSAIDs (eg. ketorolac), narcotics (eg. pethidine), sodium valproate and corticosteroids. This usually will require admission to hospital for a few days.
Since migraines are more than just headaches, associated symptoms such as nausea should be treated with anti-emetics (eg. metoclopramide). Prophylactic medication should be considered in patients who have migraines more than 2-3 days in a week. Less frequent migraines which are sufficient debilitating could also justify prophylaxis. First line medications include beta-blockers (eg. propranolol, atenolol), tricyclic antidepressants (eg. amitriptyline, nortriptyline) and calcium channel blockers (eg. verapamil). These have demonstrated efficacy and low side-effect profile. Drugs should be started at low doses and increased slowly. Prophylaxis may take up to 8-10 weeks at adequate doses to become effective in headache prevention. Other prophylactic agents include anticonvulsants (eg. valproate, gabapentin, topiramate), magnesium and riboflavin. A listing of the various acute and prophylactic agents with suggested dosing for migraines can be found in the MOH Clinical Practice Guidelines (5/2007) for the Diagnosis and Management of Headaches.
Medication overuse headaches should be addressed once recognized. The treatment of this is to withdraw the overused medication, which usually can be achieved as an outpatient, tapering over 2-4 weeks while using a long acting drug (eg. NSAIDs, prednisone) as bridge therapy. Tapering of drugs such as opioids should be done with greater caution. Prophylactic agents should be started during the acute medication withdrawal. Inpatient treatment may sometimes be necessary if outpatient therapy fails or is not safe because of co-morbid issues.
Summary
Migraines are clinically diagnosed based on typical features of the headaches and associated symptoms, either with or without aura. Secondary disorders should always be considered in all patients with headaches whose pattern does not conform to a typical benign primary headache syndrome. Investigations are indicated when such secondary headaches are suspected. Treatment for migraines, whether acute or chronic, follows evidence-based guidelines and generally have demonstrated good efficacy and tolerability. Medication overuse should be recognized and treated appropriately with supervised drug withdrawal.