MIGRAINE HEADACHES | Imperfect Understanding

 Our understanding of migraine headaches in currently imperfect.  While headache remains the most recognizable symptom of a migraine attack, it represents only one part of the disease process.  Migraine headaches typically incapacitate the sufferer, disrupt other activities and demand immediate attention.  Among people between ages 15-49, migraine represents the third leading cause of disability.

Although middle aged women bear the brunt of this disease, it tends to begin during late childhood affecting up to 10-15% of adolescents.  As many as 1 in 6 women develop migraines; among men the incidence is 1 in 12.  Overall 36 million Americans experience periodic migraine attacks.  The incidence and severity of attacks tend to peak around age 40 with a flare during the peri-menopausal years.  Infrequently the condition begins after age 50 in which case it must be differentiated from a variety of age-related neurologic disorders.

Migraines affect Caucasians more frequently than African-Americans who in turn appear more susceptible than Asian-Americans.  Attacks vary in frequency, severity and intensity not only between individuals but even in any given person.  Some experience only infrequent migraines while in others the situation may become persistent with only a rare day without headache.  Among those with episodic migraine the average number of monthly attacks ranges between 2-3.


Until recently all migraines were categorized as moderate to severe since the definition excluded less intense headaches.  Current understanding now includes headaches of all intensity.  They range from mild and relatively easily controlled with over-the-counter pain relievers to slowly evolving headaches that develop over several days to the so-called thunderclap headache representing the worst pain ever experienced.

In large measure, migraine seems to represent a genetic disorder.  When one parent suffers the disease, a child’s likelihood averages about 40%.  This increases to nearly 75% when both parents experience attacks.  Susceptibility among identical twins appears greater than in other sets of twins.  Studies detail a wide assortment of abnormalities affecting the function of a multitude of different genes.


The concept of something in the environment triggering an attack remains permanently lodged in popular thought.  Careful analysis however suggests that while some individuals may indeed be susceptible to specific triggers, for the vast majority of sufferers no identifiable link with the external environment can be demonstrated.  Commonly perceived triggers include a delayed or missed meal, bright lights, irregular sleep patterns, a peculiar odor or exposure to perfume.  Others claim their headaches revolve around consuming MSG, chocolate, red wine, cheese or nitrites present in bacon and hot dogs.  Some believe irregular caffeine intake, menstruation, birth control pills or hormone replacement therapy cause flares.

Establishing a cause and effect relationship remains difficult especially since the whole process begins with functional abnormalities of the brain’s chemistry.  The triggers may in fact represent part of the increasingly recognized premonitory symptoms.  An average of 2 symptoms occur with each attack and herald the increasingly erratic brain activity in as many as 2 out of 3 individuals.  These warning signals begin 1-2 days before the headache.  Many individuals fail to connect these rather minor, non-painful symptoms with the migraine syndrome.


“Premonitory” symptoms such as yawning, mood changes, light sensitivity, neck stiffness, fatigue and difficulty concentrating generally appear hours to several days before onset of the head pain.  Other complaints include depression, feeling excessively hot, facial flushing, perspiration or unusual pallor of the skin.


Migraine headaches generally are believed to begin with an “aura,” but actually these specific symptoms only occur in about 1 in 3 migraineurs.  Classically symptoms associated with the “aura” occur 5-60 minutes before the headache with each lasting 5-15 minutes before disappearing as the headache begins.  Visual changes predominate.  Some experience patchy loss of vision, colored or flashing lights, peculiar shapes or visual hallucinations.  Objects may become larger or smaller and appear closer or farther away – a phenomenon originally described by the migraine sufferer Lewis Carroll in his famous book Alice in Wonderland.

Other symptoms in the “aura” category include peculiar sensations or pins and needles feelings in the hand that progress to the arm, face and tongue.  At times the major symptom relates to numbness.  Most of these sensory symptoms occur in combination with visual abnormalities and resolve within less than 60 minutes.  Difficulty with speech or heaviness of the extremities without weakness appears much less frequently.

In any given individual some migraine headaches may begin with the “aura” while others occur without.  These are the classic and common migraines respectively.


Headache symptoms usually represent the most disturbing part of the process.  Generally described as moderate to severe in intensity, they tend to be confined to one side of the head principally affecting the forehead, temples and area around the eye.  Fewer individuals note neck pain.  However with time the pain progresses toward the back of the head and may become diffuse.  While one sided involvement is customary, in any given individual attacks may alternate between the left and right sides.

Migraine headaches may begin anytime during the day.  Not infrequently they will be present on awakening or alternatively may occur later in the day.  Traditionally migraine headache does not interrupt nighttime sleep.

Most describe a throbbing or pulsating pain worsened by any head movement, but up to half note some of their headaches lack the throbbing quality.  Between 50-75% describe their headaches as severe to very severe.  The intensity tends to maximize over 2-12 hours.  Less frequently only mild-moderate pain occurs which in part depends on individual tolerance; others suffer the almost immediate “thunderclap” headache with peak discomfort present immediately at onset.  Headaches generally persist for up to 24-48 hours with only half resolving within one day.  Often a quiet, darkened room speeds recovery.


Another typical feature of migraine involves nausea and/or vomiting.  In some individuals these symptoms create more distress than the head pain.  Obviously these symptoms interfere with the ability to take oral medication and often delay beginning therapy.  Another factor associated with migraine involves a slowing of gastrointestinal transport.  So even if the individual swallows the appropriate drug, absorption appears erratic and unpredictable.

Among children and adolescents a migraine equivalent may present as vertigo or dizziness associated with movement of the head.  Another frequent variant is abdominal migraine whose manifestations include otherwise unexplained, recurrent attacks of abdominal pain, bloating, nausea and either loose bowel movements or constipation.  These conditions disappear spontaneously over a period of several years.


The autonomic nervous system regularly fails to operate normally during migraine attacks.  Clinically this appears as blurred vision, stuffy nose, pale skin, unanticipated perspiration and abdominal pain or diarrhea.  Tenderness of the scalp to even light touch and a sensation of heat or cold may also develop.

Some migraine attacks may be associated with weakness of one side often combined with double vision or difficulty speaking.  These hemiplegic migraines must be differentiated from a stroke.  Retinal or ocular migraine may present with temporary, complete or partial loss of vision in one eye either with or without an accompanying headache.  Basilar migraine, once incorrectly thought due to an abnormality of an artery with the same name, appears as headache primarily at the back of the head often in combination with double vision, ringing in the ear, slurred speech and dizziness.

Sensitivity to light and sound appears at times accompanied by perception of unpleasant odors.


Resolution of a migraine headache brings another form of distress.  Known as the post-dromal phase or migraine hangover, it lasts for approximately 24 hours.  During this period the migraineur feels tired, irritable or weak.  Alternatively some experience feelings of depression or euphoria perhaps at times associated with specific food cravings.

Migraines tend to be episodic with attacks varying widely in frequency but averaging about twice a month.  Characteristically once the acute symptoms resolve, no obvious abnormalities exist until the next attack arrives.  With time and especially with excessive intake of the very same drugs employed to treat migraine, attacks tend to become progressively more frequent.  A point may occur where headaches are experienced more than 15 days each month and sometimes even daily.  Medicine Overuse Headache often masquerades as chronic migraine.


Diagnosis relies on symptoms rather than any specific test.  According to the International Headache Society at least 5 attacks are necessary with each lasting between 4 hours to 3 days in addition to at least 2 other symptoms:  headache limited to only 1 side, a pulsating or throbbing quality, moderate to severe pain and worsening with head movement.  One additional finding is required: nausea, vomiting, sensitivity to light or sensitivity to sound.

When an aura occurs, only 2 lifetime headache attacks are necessary for the diagnosis with the aura consisting of visual, sensory, language or speech symptoms followed shortly by a full recovery.  Additionally any of 2 or more findings must be present: aura symptoms spreading gradually over at least 5 minutes, 2 or more aura symptoms occurring in succession, a duration limited to between 5-60 minutes, at least one of the symptoms must be limited to one side and the headache must follow within 5-60 minutes.

Employing these criteria severely limits the type of headache labeled as migraine and in the process excludes many others that should fall within the framework.  Some of the newly recognized migraines may involve both sides of the head and present as constant, non-throbbing, mild-moderate pain.  There appears to be considerable blurring of the once clear line between tension type headaches and migraine.  Indeed these two conditions share many similarities.


Some symptoms that present as migraine headache may instead signify a more dangerous and sinister underlying ailment worthy of immediate attention.  These so-called red flags include headache associated with HIV, cancer, fever, rigid neck, progressive speech difficulty, muscle weakness and dramatically elevated blood pressure.  Abnormalities on neurologic examination, jaw pain and symptoms extending beyond 72 hours also warrant prompt medical evaluation.


Arriving at an appropriate treatment plan depends on timing, frequency and severity of the attacks.  Typical nostrums suggest attention to proper sleep, stress reduction, engaging in sufficient physical activity and avoidance of any specific factors that seem to exacerbate the situation.  Whether these actually provide benefit or merely function as placebo remains undetermined.

For mild to possibly moderate symptoms, many achieve relief with over-the-counter pain relievers.  Examples include acetaminophen (Tylenol), aspirin or any of the non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen.  Combination with caffeine might be beneficial since this common ingredient of coffee, tea and some pain relievers assists in correcting delayed absorption from the stomach and intestine.


Time for a pill?
Many options exist for migraine headache

For more severe attacks, earlier commencement of treatment provides rapid benefits and may significantly shorten the course.  Currently triptans remain the mainstay of treatment.  These derivatives of tryptamine became available in the early 1990s and currently include Imitrex, Zomig, Maxalt, Relpax, Amerge, Frova, Sumavel, Zecuity and Axert.  Treximet combines the sumatriptan of Imitrex with the NSAID naproxen.  These unnecessarily expensive medicines may be delivered orally as standard tablets or alternatively as rapidly dissolving pills.  In other circumstances the drug may be injected with or without needles or taken either as a rectal suppository or nasal spray.

Originally thought to function by constricting blood vessels, these drugs instead provide relief by interacting with the brain’s serotonin metabolism.  While they often dramatically reduce the course of disease, due to cost and insurance company restrictions, people tend to delay initiating therapy.  Treatment even at the onset of a headache is already suboptimal since the actual disease process commences long before the headache appears.  About half of patients receiving a triptan note less than desired improvement, a situation partially corrected simply with more attention to timing.  No studies confirm specific benefits of one triptan versus another.


Other treatment options include the ergot preparations, specifically DHE or dihydroergotamine, by injection under medical supervision.  Intramuscular injection of either Ketrolac or aspirin attached to lysine also provide rapid relief.  A related preparation, Dexketoprofen remains a popular alternative treatment in Europe.

Many patients with migraine headache congest emergency rooms in search of relief.  Treatment with the opioids, once common, has fallen out of favor in large measure since the drugs fail to provide sufficient benefit to risk ratio and possess significant addictive potential.  Morphine, butorphanol, tramadol, hydrocodone, oxycodone and codeine generally should not be prescribed.  Similarly the once popular relative of phenobarbital known as butalbital finds itself on the avoid list.

Appropriate attention to combating nausea and vomiting utilizes drugs such as prochlorperazine, odansetron or metoclopramide.  Not uncommonly these gastrointestinal symptoms prove more disabling than the headache.  As an additional benefit some of these anti-emetics provide an additional layer of pain relief.


When symptoms occur with sufficient frequency or cause untimely incapacitation, preventive therapy may offer some value.  Among the most popular drugs in the preventive category are beta blockers (metoprolol, atenolol, propranolol) originally designed to slow the heartbeat and reduce blood pressure.  The anti-seizure medicines topiramate (Topamax) or Depakote (divalproex sodium) also find widespread use.  Other oral agents include old fashioned tricyclic anti-depressants (amitriptyline, nortriptyline) or the newer SSRI versions (Paxil, Prozac). Injections of Botox may assist in prevention.

None of the drugs prescribed for preventive purposes were specifically developed to address migraines; coincidence demonstrated their benefit.  Unfortunately none work exceptionally well with a 50% reduction in frequency of symptoms over a period of months equating with success.


Occasionally vitamins or herbs ward off recurrences.  Among them are feverfew, petasites or butterbur, riboflavin, magnesium, melatonin and coenzyme Q10.

Once on the list of favorites, neither gabapentin nor verapamil currently appear sufficiently helpful to generate much enthusiasm.


new ideas always needed
Research into migraine headaches contiues

Just evolving and eagerly anticipated is a potential advance in migraine headache prevention.  It blocks the action of an apparently central component involved in the genesis of the migraine constellation.  Known to block the action of CGRP – calcitonin gene related peptide – these drugs are delivered by injection several times a year in a manner akin to popular therapies for rheumatoid arthritis and psoriasis.  Unfortunately the anticipated nearly $10,000 cost will significantly impair utilization.  While these drugs dramatically reduce the frequency of attacks, only about 15% of patients remain totally migraine-free.

Over the years our thoughts regarding the cause of migraine headacheshas substantially evolved.  Until recently blood vessel constriction followed by dilation was believed to be a central property of the headaches with triptans and ergotamines acting to constrict the vessels.  Firm evidence now implicates an underlying sensitive and vulnerable brain with periodic discharges of neurotransmitters – chemicals produced by certain nerve cells meant to act on other neurons.  The central fault relates to the dysfunction of channels that allow ions to enter certain brain cells or neurons more easily than expected. The trigeminal nerve, hypothalamus, thalamus and brainstem seem intimately involved.  All of this neuron-neuron cross talk leads to a sterile exudate of plasma proteins in the vicinity of blood vessels in the dura mater after which the pain begins.

Research into the genesis of migraine headaches continues apace.  As the basic physiology of the relevant brain structures gives way to scientific probing, our ability to counteract this troubling condition will offer new avenues of treatment.  The major foreseeable downside involves cost.  Pharmaceutical companies must please shareholders; insurance companies can no longer tolerate millions of people requiring drugs costing 5 and 6 figures.  Hopefully compromise is imminent.

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