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 MigraineMigraine 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 lightor 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, includingheadache history

• Physical exam

• Potential additional evaluations

• MRI (magnetic resonance imaging)

• CT (computed tomography) scan

• Other

• Possible referral to a specialist

• Neurologist

• 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 won’t 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 doesn’t 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 MOA’s

• 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)