Management of

Migraine

Migraine
A migraine is a severe painful headache that

is often
preceded or accompanied by sensory warning signs such as
flashes of light, blind spots, tingling in the arms and legs,
nausea, vomiting, and increased sensitivity to light and
sound. The excruciating pain that migraines bring can last for
hours or even days.

History of Migraines

Have been with us for at least 7,000 years.

In ancient Greece, Galen attributed these painful headaches as ascent of
vapors or humors from the liver to the brain. He called them Hemicranias.

Hemicrania Megrim Migraine

In the 17th century, the idea of rising humors was replaced by increased
blood flow.
In the 1980s, Harold G. Wolff of New York-Presbyterian Hospital, said that
migraine pain stems from the dilation and stretching of brain blood
vessels, leading to the activation of pain-signaling neurons

What Actually Happens During a

Migraine?
Brain Scans suggest that Migraines arise from an increase in

blood flow of about 300% PRECEDING the headache.

Circulation and blood flow appear normal during the
headache.
Also thought to arise from a disorder in the nervous system
affecting the brainstem.

Phases of Migraine
Migraine are more than just pain

Prodrome

Stage of Migraine that is characterized by difficulty

concentrating, yawning, fatigue and/or sensitivity to light and

noise.
Duration: A few hours to a few days

Aura

Stage of migraine that is characterized by visual illusions of

sparks and lights, often followed by blind or dark spots in the

same place as the bright hallucinations
Duration: 20-60 minutes

Possible Physiology of Aura

Neuronal activity is controlled by Na, K, and Ca flows across nerve

cells through pumps and channels.
Pumps Resting Cells: High K and Low Na and Ca
Channels open inc. Na and Ca flow (depolorizes membrane) Cell
is more pos on inside than outsideA Neuron Fires
Neurotransmitters are released.
Normally, cells then briefly hyper-polarize: they become strongly
negative on the inside relative to the outside .

Hyperpolarization closes the sodium and calcium channels and returns the neurons
to their resting state soon after firing.
But neurons can remain excessively hyperpolarized, or inhibited, for a long time
following intense stimulations.
The phases of hyperexcitability followed by inhibition that characterize cortical
spreading depression can explain the changes in blood flow that have been
documented to occur before migraine pain sets in.
When neurons are active and firing, they require a great deal of energy and blood
just what investigators see during brain scans of patients experiencing aura.
But afterward, during inhibition, the quiet neurons need less blood.

Headache
Stage characterized by excruciating or throbbing pain along

with sensitivity to light and sound.

May be accompanied by nausea and vomiting
Sometimes only half of the head or part of the head is in pain.
Duration: 4 72 hours

Postdrome
Characterized by:

sensitivity to light and movement

Lethargy
Fatigue
Difficulty focusing

Also called a zombie phase

Duration: A few hours to a few days

Migraine Pathophysiology

Migraines are triggered by internal (dehydration, lack of sleep, stress) or

external stimuli (smell, light, food)
Deep nuclei in the brainstem begin to malfunction (trigeminal nucleus
and Magnus raphe nucleus)
Energy failure allows the nerves surrounding vascular structures in the
brain (which are part of the trigeminal nerve) to propagate the problem
and malfunction (throbbing pain)
These malfunctioning nerves trigger thalamic dysfunction (nausea,
severe pain)

Migraine Genes
Migraines are a Genetic condition

- 3 genes discovered in past year

- EAAT2 affects glutamate removal from synapse
- TRSK is a potassium channel in nerves
Gene discoveries support the concept that migraine is
caused by nerves that are hypersensitive

Some Common Symptoms

of Migraine

Before or during an attack

Feeling of well-being or surge of energy

Talkativeness or restlessness
Increased appetite
Drowsiness or depression
Irritability or tension

During an attack

Nausea, vomiting,
or diarrhea

Sweating or cold hands

Sensitivity to light
or sounds

Scalp tenderness
or pressure pain

Pale color
Pulsing pain

Types of Migraine

Migraine with Aura

Migraine with aura is accompanied by visual or sensory

symptoms that disappear completely after a headache

attack. Visual symptoms include flickering lights, spots, or
lines or vision loss. Sensory symptoms include pins and
needles or numbness. In addition, patients may experience
speech disturbances. This picture shows an example of a
visual symptom known as a fortification spectra which may
be experienced during aura.

What Causes Migraine?

Migraine Triggers
Missing a meal or dehydration
Sleep (too little or too much)
Caffeine
Stress
Weather/Barometric Pressure Changes
Menses/ Hormonal changes
Fatigue
Exposure to environment (light, sound, smells)
Head trauma
Dietary triggers (Chocolate, nitrates, MSG, Aged cheeses, Alcohol , Nuts, Processed
meats, Citrus)

How Is Migraine Diagnosed?

Complete medical history, including
headache history

Physical exam
Potential additional evaluations

MRI (magnetic resonance imaging)

Neurologist

CT (computed tomography) scan

Other

Possible referral to a specialist

Other specialist

Management of Migraine

Five Principles of Migraine

Management
Treat occipital neuralgia and trigeminal nerve dysfunction
Avoid Rebound headache
Abortive therapy
Preventative therapy
Lifestyle Issues

Treat Occipital Neuralgia

Trigeminal Nerve

Avoid Rebound Headache

(medication overuse headache)
In general if acute meds are used more the 3 days per week
they will cause rebound headache.
This HA is usually a dull constant HA
Treatment: Tough love- stop taking meds completely

Things might get worse for 2 weeks but then will improve
The worst offenders: Narcotics, Excedrin, Fioricet, butalbital
containing meds
This may also keep headache preventive medications from
working well.

Acute (abortive) migraine treatment

principles
Treat early, while headache is building
Use correct dose and formulation
Limit to 3 days per week (with exceptions)
Try drug with at least 2 headaches to see if it works before

moving on to another agent

Use drug combinations often work when a single agent wont
work

Acute treatment options

Specific
Triptans, e.g., Imitrex, Maxalt, Zomig, Relpax, ect
Ergotamine/DHE; Migranol

Nonspecific
NSAIDs
simple analgesics
combination analgesics
Anti-Nausea meds

The Triptans
First introduced in the 1990s
Their action is attributed to their binding to serotonin 5-HT1B

and 5-HT1D receptors in cranial blood vessels that causes

constriction and subsequent inhibition of pro-inflammatory
neuropeptide release.
They are effective because they act on serotonin receptors
in nerve endings as well as the blood vessels. This leads to a
decrease in the release of several peptides, including CGRP
and substance P.

Sumatriptan Mechanism of Action

Sumatriptan is a 5HT receptor agonist.

Sumatriptans were first administered subcutaneously, then
orally and now its available in nasal spray

The Ergots
Ergots are also 5HT 1B and 1D seratonin receptor agonists.
They are very old drugs.
Often cause more side effects than Triptans but are longer lasting.
Ergots in use include:

DHE (Dihydroergotamine mesylate)

Ergotramine Tartrate
Cafergot
Isometheptane

Dihydroergotamine mesylate (DHE)

Mechanism of Action
Binds to noradrenaline and dopamine receptors.
Stimulates vasoconstriction by stimulating alpha-adrenergic
and serotonin receptors

Has high affinity for 5-HT 1,2 receptors.

Activation of 5HT1 Vasoconstriction Migraine relief.

The Future of Antimigraine Medication

Magnesium
Noritriptan
Combination of antidepressants, antihypertensive, and antiepileptic drugs.
Drugs that target trigeminal neurotransmitters like glutamate and Nitric

Oxide.
Transcranial Magnetic Stimulation: A handheld device that transmits brief
pulses of magnetic stimulation is being evaluated for the treatment of
migraine with and without aura.

Magnesium
In clinical trials
Thought to stabilize the sodium potassium pump.
Reported that Low levels of Magnesium may be responsible
for release of NMDA receptors which leads to spontaneous
discharge and CSD.

Donitriptan

Has equal affinity to both 5HT 1a and 1d.

It is ten times more effective than sumatriptan, naratriptan

Rational polytherapy
NSAID plus Triptan
Antiemetic (metoclopramide 10 mg) plus NSAID (Naproxen
sodium 550 mg)
Antiemetic plus triptan
Antiemetic plus NSAID plus triptan

Mechanism of Action of Aspirin in

Migraine Pain Relief
Aspirin is a pain reliever.
In Migraines it is thought to
Inhibit effects of the trigeminal
nerve inputs thereby reducing pain.

Prophylactic Medications

For those patients who experience severe and complicated migraines more than 2 times a
month.
Three categories
Anticonvulsants
Topiramate (Topamax)
Antidepressants
Verapamil or Nortriptyline
Antihypertensives
Propranolol or Venlafaxine
If one doesnt work then it is given in combination with the others.

Anticonvulsant Prophylactic Drugs:

Topiramate MOA

How does Topiramate work?

Topiramate is an anticonvulsant that treats partial-onset and
primary generalised seizures.
It has multiple MOAs
Blocks Sodium Channels
Enhancement of GABAa receptor mediated inhibition.
Antagonism of glutamate
Inhibition of high voltage activated calcium channels.

Antihypertensive Prophylactic Drugs:

Propranolol
Central action of propranolol mediated by inhibition of central

B-receptors interfering with the vigilance-enhance

andrenergic pathways.
Interacts with 5-HT receptors

Antidepressant Prophylactic Drugs:

Nortriptyline

It inhibits the reuptake of norepinephrine (noradrenaline)

and, to a lesser extent, serotonin.
5HT 2A antagonist
Side effects: dry mouth, constipation,sedation and increased
appetite.

Preventive med principles

No set rule on when to use, but consider use when severe

headache occurs once a week

In order for preventive meds to be most effective, limit acute
meds to 3 days per week

Make sure to use an appropriate dose

At least a 2 month trial at a proper dose is required
Goal is to decrease headache freq by 50%

Prepare for side effects first, benefit later

Reliable birth control
Keep trying until you find one that works
Preventives are not always lifelong treatments-can be

tapered off after several months when frequency of headache

decreases

Natural Preventatives
ButterBurr Root (be careful of source)
Feverfew
Magnesium
Alpha-linolenic acid and Gamma-linolenic acid
Vitamin D, E, B12, B2
alpha lipoic acid
L-Carnatine
Fish oil
Co Q10

The preventive alphabet

Antidepressants: nortriptyline, amitriptyline, Cymbalta
B-blockers: propranolol, atenolol, nadolol
Calcium channel blockers: verapamil
Depakote (valproic acid)
Epilepsy meds (other than Depakote): gabapentin,
topiramate, Lyrica
Misc: tizanidine, Namenda

Botox Treatment
Botox Injections- Approved by FDA in Oct 2010!
Approved for chronic migraine (migraine headaches

happening more than 15 days/ month)

32 injection sites in forehead, temples, shoulders and neck
Many insurance companies are still fighting not to cover this

Lifestyle Management
Sleep 8 hours consistent schedule
Eat 3 regular meals (or more) per day
Drink lots of fluids
Get Aerobic exercise regularly

Limit caffeine (or better yet avoid completely)

Identify your triggers
Keep a headache diary
Manage stress
Use correct posture and pause during repetitive activities

Nonpharmacologic Treatments
Biofeedback
Relaxation therapy
Cognitive Behavioral Therapy
Acupressure
Acupuncture
Physical Therapy
Chiropractic treatment

Additional Treatment Measures

Occipital Nerve Stimulators
TENS units
Transcranial Magnetic Stimulator
Special Diets

Transcranial Magnetic Stimulation

The premise is that this technology, called transcranial

magnetic stimulation, or TMS, may interrupt cortical

spreading depression and possibly prevent pain from arising
or progressing.

Transcranial Magnetic Stimulator

(TMS)