The science of migraine "It's all in your brain" - Dr Elizabeth Leroux, MD, FRCPC Neurologist, University of Calgary SAIT, Calgary November 20th ...
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The science of migraine
«It’s all in your brain»
Dr Elizabeth Leroux, MD, FRCPC
Neurologist, University of Calgary
SAIT, Calgary
November 20th 2018
Disclosures I have received payments from these companies for my role as a speaker, consultant or board member: Allergan Eli Lilly Novartis Teva ** I am not paid to give this presentation
Why am I giving this talk? • It’s only a headache… • Nothing is seen on the MRI, so you’re making it up • Migraine is a pretext that whiny people use to avoid work • Migraine is a neurotic problem for hysterical women
Why am I giving this talk?
Have you tried…
drinking water
and salt? It must be the
chocolate
My mother said «lie
down, it’s going to get
better»
Manage your
stress my dear
I know the cause of
migraine and I will
cure you!
NO unique cause
for migraine
NO 100% cure for
migraine
(I wish…)
You are not alone
12% of the world’s population has migraine
1-2% has CHRONIC migraine
What is the cause of migraine? Is it really all in my head?
Migraine
«Easy diagnosis»
Recurrent attacks
Disabling
Nausea/vomiting/sick
Light/sound sensitivity
NO other cause
The Headache
What is migraine?
More than «just a headache»
Visual Headache may be
Aura One-sided
Throbbing Disabling
Neck pain Slows down
activities
Lasts >4 hours
Gastro-intestinal upset
Nausea, vomiting
Diarrhea Recurrent
attacks
Sensory
hypersensitivity
Dizziness Lights
Vertigo Sounds
Cognitive Smells
difficulties Movements
Brain Fog
9
Migraine is invisible on CT and MRIs
Computer
Visibly Brain
tumour
broken
Hardware
Computer Chronic
seems migraine
normal Normal
Software CTWhat is a gene again?
How does the Electric current brain work? Chemical substances
Genes
Proteins
Neurotransmitters Receptors Ion channels
How your
brain worksSensory fiber
The blind men and the elephant
What we’re Structure or mechanism Research tools
observing
Macroscopic Brain matter, meninges, CT Scan
arteries.... MRI
Electricity Electric activity in cells Electrophysiological
recordings
Chemistry Proteins Blood levels
Neurotransmitters Biomarkers
Ion channels
Metabolic Blood flow in real time in Functional MRI
activity certain zones PET scan
Genetic DNA, chromosomes Gene testing
Genome wide scanAversion to light box
Model for
photophobia
Pain model of
the rat’s faceThe human model to study migraine Courageous volunteers in Denmark
The migrainous brain is different
Predisposing
«gene mix»
Chemistry Electricity
Low serotonin Low habituation
to stimuli30 days, 3 migraine attacks The Migraine Cascade seen on fMRI Ammonia odor (nociceptive) Rose odor (olfactive) Checkerboard stimulation (visual) Schulte & May, Brain 2016
I feel the pain… Where does it come from?
Meninges and blood vessels are filled with sensory nerves and can cause pain
Inflammation is in the brain!
I have pain in my neck during my migraine...should my neck be fixed?
Posture and the neck
Myocardial infarction:
an example of referred pain
• Heart lacks blood
• Pain is felt in the armHead and Neck: a two-way road
60% of migraine patients
report neck pain during an
attack V1
The electrical pathways for
neck and eye-front are linked C2
C3
Migraine can be felt in the C2-3
neck V2-3
Neck pain/tension can trigger
migraineA two-way road between head and neck
Many vicious circles
«The Ping Pong theory»
Overuse Mood
Sleep
Sinuses
NECK
BruxismThe Periphery
Sinus
TMJ
Neck
(mood)
Raise the tolerance of the brain Decrease the irritating input,
Medication treat the peripheral issue
Stabilizing lifestyleYOU are not crazy
Migraine is real
(and it’s complicated….)
• Migraine is a neurological disorder with
documented chemical and electrical
mechanisms.
• All this cannot be seen on ordinary CT scans
and MRIs…but it will appear on a headache
diary.What type of migraine do you have?
Aura Triggers
Visual, sensory,
speech, weakness Long list...
Frequency
/month Disability
1-6
7-14
Migraine Personal life
Work
15 + School
Symptoms
Nausea Severity
Hypersensitivy
Neck pain Medications Intensity
Duration
Dizziness Frequency of meds
**Opioids
33You global medical history is important
Vascular OBGYN
Stroke, CAD, Dymsenorrhea, contraception,
Raynaud’s, POTS, pregnancy, menopause
hypertension, low BP
Neurology
Psychiatric Epilepsy, MS
Anxiety, depression, abuse, Migraine Brain
addiction, PTSD, ADHD,
personality, coping style Body
Psyche Respiratory
Asthma, sleep apnea
Inflammatory
Crohn’s, arthritis, eczema
Vestibular
Other pain Meniere’s, BPPV
Car sickness
Fibromyalgia, pelvic pain,
neck pain, post-trauma, IBSNo one size fits all
Migraine is a very diverse
condition
• Symptoms
• Triggers
• Medical history
• Severity and frequency
• Response to treatmentsThe Migraine Tree: a roadmap to a jungle of information
Acute treatment Preventive
Special Treating individual Pharmacologic
Situations attacks as they come Lower attack frequency
Life with migraine
Procedures
Lifestyle and Neuromodulation
behavioral Acute and preventive
Care for migraine brain
Migraine basics
Expectations
Diary
How to try tx
Work/Life Psychological
Social network background
Women Medical
and children Migraine
background
SubgroupThe Migraine Tree: content of the branches
Lifestyle Life situations Acute Preventive Procedures
Modulation
Diary Work Acetaminophen Amitriptyline Acupuncture
Sleep Travel NSAIDs Propranolol Botox
Diet School Triptans Nadolol Injections
Pacing Partner / kids Anti-nausea Candesartan Blocks
Relaxation Friends Opioids Topiramate Cefaly
Exercise Driving DHE Magnesium TENS
Triggers Disability Caffeine Vitamin B2 Ice packs
Glasses Emergency Mint rollers CoQ10 Heat
Migraine kit Support Salt Water Valproate
Cannabis
CGRP MABIf I avoided all my triggers, would my migraines disappear?
The lists of triggers are so long....I’m going crazy trying to avoid everything!
What can I eat???
The migraine brain is influenced by many factors at every moment
Cognitive bias, variations
Establish a link between events is not
that easy!
Temperature
Wine
Barometric pressure
Migraine MigraineThe Curelator APP results Beliefs True associations The influence of individual triggers tends to be overestimated BUT adapting lifestyle is still important. A difficult balance! 43
Migraine Trigger Threshold Theory
• Regular
lifestyleMigraine, the asthma of the brain
Asthma Migraine
Hyperexcitability of the lung Hyperexcitability of the brain
Mild
Triggered by exercise only
Avoid exercise
Severe
Triggered by normal living
Need for medication
Acute and preventiveCan we avoid living? • Some triggers cannot be avoided • Chasing every trigger may increase anxiety • Some triggers are maybe overestimated – Periods, food, stress, weather It may be best to focus on protective behaviors instead of trigger avoidance Migraine is a real disease that often cannot be controlled by lifestyle only
Migraine has an impact on my family...am I the only one?
Impact of migraine on family life
Study on 4022 couples with a migraine patient
100
Buse, Mayo Clin Proceedings 2016
80
60
Chronic
40
20 Episodic
0
A B C D E F G H
A: Missed one day of family activity over the last month
B: Missed 4 days or more of family activity
C: Spouse does not believe that patient has migraine
D: Does not enjoy family activities 4 days or more
E: Missed an important family event or religious event
F: Patient thinks that he/she would be a better spouse without migraine
G: Partner is irritable or angry because patient has migraines
H: Patient is worried by his financial stability because of migraineMigraine has an impact on work
Young, the stigma of
migraine, PLOS 2013Salt and Water for Migraine?
Can placebo work THAT WELL?
Placebo in migraine prophylactic trials
70
60
50
40 Oral
30 Acupuncture
Surgery
20
10
0
Oral Acupuncture Surgery
Meissner K, et al. Differential effectiveness of placebo treatments: a systematic review
of migraine prophylaxis.
JAMA Intern Med. 2013 Nov 25;173(21):1941-51.Do we care if it’s a placebo?
Maybe it will work for ME!
• Is it safe?
• How much does it cost?Why is nothing working for me? I’m so fed up with drug trials...
Why is nothing working for me?
I’m so fed up with drug trials...
Class Medications Commercial name Doses /24h
Anti-depressants Amitriptyline Elavil 10-100 mg
Notriptyline Aventyl 10-100 mg
Venlafaxine Effexor
Anti-convulsants Topiramate Topamax 25-200 mg
Gabapentin Neurontin 300-3600 mg
Valproic acid Epival 250-1000 mg
Anti-hypertensives Propranolol Inderal 40-160 mg
Nadolol Corgard 40-160 mg
Candesartan Atacand 8-32 mg
Lisinopril Prinivil
Natural supplements Magnesium 600 mg
Vitamine B2 400 mg
Coenzyme Q10 300 mg
Petasites (butterbur)
Others Flunarizine Sibelium 10 mg
Pizotifene Sandomigran
Botox 56Responder rates in prevention trials:
No miracles and many side effects
70
60
50
40
30
50%RR Pl
20 50%RR Rx
?
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Pringsheim, Prophylactic Guidelines, CJNS 2012 supplSometimes migraine can be refractory and
disabling despite all best efforts
(behavioral and pharmacological)What about CGRP... I heard about new treatments?
Antibodies to treat diseases
CGRP and migraine why should we block it? will it cure migraine?
Results of the CGRP antibody trials • Mechanism of action is specific to migraine • AS effective as existing preventives • Some people respond very well – 75% less migraine • Much better tolerated, almost no side effects • Effect is seen faster (as early as 1 week!) • Safety: so far no alarming signal
CGRP antibodies in practice • Once per month injection, probably at home • Cost is likely to be 7000$ per year – NB We pay 50K for multiple sclerosis • Novartis has organized a patient support program: Aimovig GO • Neurologists will be able to prescribe • Future antibodies include Ajovy and Emgality (Teva and Eli Lilly) • Expected in Canada in? 2019
Everyone seems to talk about annabis... Should I try it?
489 chemical
compounds
THC
CBD
90 others: cannabigerol, cannabichromene,
cannabidivarin cannabidiolic acid
80 terpenes
flavonoidsIzzo, 2009
Medical cannabis:
THC & CBD Doses and ratios
Can we get standardized products?
Very high variability in the
content of THC and CBD in
oral preparations used in
Italy.
• 12% THC • 13% CBD
Some patients end up using
• Psychoactive • Not Psychoactive subtherapeutic doses.
• Sleep- • Wakefulness-
inducing promoting (Pellesi 2018)Published evidence:
Baron, JHP 2018
Cannabis for migraine
• Donovan M (1845) On the physical and medicinal qualities of Indian hemp (Cannabis
Indica); with observations on the best mode of administration, and cases illustrative
of its powers. Dublin J Med Sci 26:368–461
• Reynolds JR (1868) On some of the therapeutical uses of Indian hemp. Arch Med
2:154–160
• Waring EJ (1874) Practical therapeutics. Lindsay & Blakiston, Philadelphia
• Ringer S (1886) A handbook of therapeutics. H.K. Lewis, London
• Hare HA (1887) Clinical and physiological notes on the action of cannabis Indica.
There Gaz 11:225–228
• Suckling C (1891) On the therapeutic value of Indian hemp. Br Med J 2:11–12
• Mikuriya TH (1991) Chronic migraine headache: five cases successfully treated with
marinol and/or illicit cannabis. Schaffer Library of Drug Policy, BerkeleyEFFECTS OF MEDICAL MARIJUANA ON MIGRAINE HEADACHE
FREQUENCY IN AN ADULT POPULATION
Retrospective chart review from 2 cannabis clinics in
Colorado
Migraine
N=121 patients with migraine, at least 1 follow-up Frequency
Migraine frequency = patient reported (no diaries)
2%
Delay between initial and most recent: 1-3 YEARS 12%
85% report a decrease in frequency
Baseline 10.4 / month à Decrease to 4.6 / month 85%
BUT Decreased Unchanged
Increased
20% report migraine prevention as a positive effect Rhyne, Pharmacotherapy 2016
11.6% report a benefit as abortive
NO check for other interventions during follow-up.
70Maybe via sleep and anxiety?
Predisposing Precipitating Perpetuating
Trigger
Accident
Menopause Sleep disorder
Major stress
Other disease
Episodic status Attacks Stress
increase Anxiety
Caffeine
Overuse
Chronic state Muscle
Disability tensions
Adapted from Dr Anne CalhounConclusions on Cannabis • Could be helpful for people who have sleep difficulties and anxiety • May help to withdraw opioids • Virtually NO evidence • Very strong marketing • Mix between real science and excessive claims • MORE RESEARCH NEEDED !
The Migraine Tree: many options for you
Acute treatment Preventive
Special Treating individual Pharmacologic
Situations attacks as they come Lower attack frequency
Life with migraine
Procedures
Lifestyle and Neuromodulation
behavioral Acute and preventive
Care for migraine brain
Migraine basics
Expectations
Diary
How to try tx
Work/Life Psychological
Social network background
Women Medical
and children Migraine
background
SubgroupIf you suffer from asthma, a recognized chronic disease
Well established management programsIf you suffer from migraine…
What do you have access to?
• The ONLY multidisciplinary program for headache in
Canada was in Calgary.
• It was called CHAMP.
• It had education sessions, lifestyle assessment,
workshops, and access to physios, occupational
therapists, kinesiologist, psychologists, dedicated
pharmacist.
• It has been cancelled this year. The funding went to the
Chronic Pain Center where there is no specific
headache program.
• An unfortunate decision.Why are waiting lists for headache
clinics SO long?Where is the canadian association for migraine??
We need more patient advocates • Migraine patients are stigmatized • Many feel guilty of being «limited» or «weak» • The only way to move forward is to unite, speak up and get organized • Fund resesarch
Education advocacy Research Support
www.migrainecanada.org
migrainecanada@gmail.comConclusions • Our scientific understanding of the migraine symptoms is progressing • There is NO one-size-fits-all for migraine • Managing migraine requires a global approach, managing triggers is not often enough • The placebo effect can work, but we must be aware that it is placebo • Some patients do not respond to current therapies and are severely disabled • CGRP antibodies are a new class of migraine preventives • There is no sufficient scientific evidence to recommend cannabis for migraine at present time • Migraine Canada will develop!
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