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Migraine Headache – Update on Diagnosis & Treatment
Herbert L. Muncie, Jr., M.D.
What is the diagnosis?
Sarah, a previously very healthy 14 year old female complains of a severe headache & nausea. It is the start of the Thanksgiving holiday and all she wants to do is lay on the sofa. PMH
H. flu meningitis age 7 months Car motion sickness as a child
Family history positive for migraines – maternal grandmother & mother
Diagnosing Migraine Headache Any severe or recurrent headache most
likely is a form of migraine Almost all patients will have family history
of migraines or at least “sick” headaches Only 15% have preceded or accompanied
focal neurologic symptoms Usually visual
Vision loss or distortion in one eye – ‘ocular migraine’
“Classic migraine”
Sarah
Spent most of Thanksgiving holiday resting on the sofa
Diagnosed with onset of migraine headaches
Recurrent Headaches Primary
Migraine Tension Cluster Other benign – cough, cold temperature,
post coital, exertion
Recurrent Headaches Secondary (pain from complications)
Intracranial tumor Intracranial aneurysm Intracranial A-V malformation Temporal arteritis
Migraine with aura – Criteria*
At least 2 attacks with 3 of the following: Fully reversible aura symptoms At least 1 aura symptom develops gradually
during more than 4 minutes or 2 symptoms occur in succession
Any aura symptom lasts less than 60 minutes
Headache follows the aura within 60 minutes
*International Headache Society - 2004
Migraine with aura
Visual aura common Slowly evolving scintillating scotoma that
moves or passes through visual field Duration of aura – 22 minutes Should not be called ocular migraine if
bilateral eye involvement Just call them migraine with aura
Migraine with aura – vascular risk?
Migraine with aura is associated with 2 fold risk of ischemic stroke & cardiovascular event Absolute risk is low (4 per 10000 women
years) May be indication for aggressive treatment
of other risk factors Unclear if more intense treatment &
prevention of migraines will alter the risk
Migraine without aura – Criteria*
At least 5 attacks (bunch of them) Lasting 4-72 hours untreated or unsuccessfully
treated (didn’t just go away quickly) Must have one of these to be migraine:
Nausea or vomiting Photophobia Phonophobia
*International Headache Society - 2004
Migraine without aura – Criteria* Then usually have at least 2 of these:
Unilateral pain Throbbing/pulsating Aggravation on movement Moderate or severe intensity
And of course to be sure not something else: H & P does not suggest organic disorder H & P suggests an organic disorder which is then
ruled out An organic disorder is present but attacks do not
occur for the 1st time in close time to the disorder
*International Headache Society - 2004
Diagnosing the acute headache The classification criteria are best suited for a
between-attack assessment of their typical headache However, they are often used for the acute attack Once acute pain relieved, take time to make an
accurate diagnosis
Up to 1/3 of ED patients cannot be assigned a diagnosis Despite a through questionnaire-based
assessment
ER Clinical Decision Rule
“ID Migraine” – three features Sensitivity to light Nausea or vomiting Disabling intensity of headache
0 - 1 positive - low probability If 2 positive higher probability of migraine
Criteria focus on typical attacks not the current acute attack
Epidemiology - Migraine
Can start at any age, however, Peak incidence of onset is mid-adolescence
(age 13-16) History of colic or motion sickness support Dx
Median frequency - 1.5/month Greater increase in prevalence with aging in
women Females - 6.4% age 12 - 17; 17.3% age 18 - 29 Males - 4.0% age 12 - 17; 5.0% age 18 – 29 Usually more severe in women
Pathophysiology
Migraine is a primary neural event Something lowers threshold for a cortical
spreading depression (CSD) Which causes regional hypoperfusion (aura) Release of proinflammatory neurochemicals
Neural event results in vasodilation Which leads to pain & more nerve activation
Migraine headache is not a primary vascular event
Testing Indications* Laboratory tests not helpful or needed to
make the diagnosis EEG not indicated as routine evaluation Neuroimaging guidelines
Typical migraine with normal neurologic exam Neuroimaging not warranted (SOR-B)
Insufficient evidence regarding imaging in presence of neurologic symptoms (SOR-C)
*U.S. Headache Consortium (2000)
Neuroimaging - EBM
For non-acute HA with unexplained abnormal finding on neurologic examination – obtain neuro image (SOR-B)
If atypical features or headache does not fulfill definition of migraine – lower the threshold for obtaining imaging (SOR-C)
CT vs. MRI? Insufficient data to recommend MRI compared to CT
in evaluation of migraine or other nonacute headache (Grade C)
Red Flags!
Strongly consider neuroimaging if New onset > age 50 Thunderclap onset Focal and nonfocal symptoms Abnormal signs Headache with change in posture Valsalva headache HIV or cancer diagnosis
Treatment Goals of treatment
Reduce frequency, severity, & duration of headaches
Improve quality of life (QOL) Avoid acute medication escalation
Treatment Guidelines are based upon having a specific diagnosis Often difficult initially to make specific Dx Therefore, significant uncertainty about ‘best’
initial treatment
Treatment - Migraine The brain of patients with migraines does not
tolerate peaks or troughs of life Patients should get:
Regular sleep Go to bed and awaken same time every day
Regular meals Eat same time every day Never skip meals – fasting associated with
precipitating headache Regular exercise Avoid peaks of stress, troughs of relaxation Avoid unique dietary triggers
Migraine & Diet - EBM
Frequency, duration & severity are NOT increased by dietary choices (SOR-A) Cheese, alcohol, chocolate, citrus are not
universal triggers Low-fat diet reduced frequency of
migraines (SOR-B)
Migraine & Supplements - EBM Supplements reduced frequency & intensity
Riboflavin – 400 mg qd Effect begins at 1 month, maximal @ 3 months
Magnesium – 600 mg qd Diarrhea common - almost 20% 360 mg qd during luteal phase reduced menstrual migraine
Others Butterbur 100-150 mg/d CoQ10 300 mg/d Feverfew 18.75 mg/d
National Guideline Clearing House SOR – A http://www.guideline.gov/summary/summary.aspx?doc_id=6231&nbr=004002&string=migraine
22 yo female presents with throbbing headache, nausea, photophobia for 5 hours. BP 116/76, P 86. Which of these treatments would be appropriate for her?
Question
a. Ketorolac (Toradol®) 60 mg IM
b. Metoclopramide (Reglan®) 20 mg IV
c. Prochlorperazine (Compazine®) 10 mg IV
d. D.H.E. 45 1 mg IV
e. Sumatriptan (Imitrex®) 6 mg SQ
Treatment of Acute Pain
NSAID (SOR-A) Ketorolac (Toradol®) – 10 mg oral, 60 mg
IM, or 30 mg IV(SOR-C) Combinations
Isometheptene mucate, dichloralphenazone and acetaminophen (Midrin®)
Butalbital has not been effective in controlled trials (butalbital/acetaminophen/caffeine- 50/325/40 Fioricet®, butalbital/ASA/caffeine-50/325/40 Fiorinal®)
Treatment of Acute Pain
NSAIDs – more effective when: Taken early With adequate initial dose Combined with antiemetic
ASA 1000 mg Combined with metoclopramide IM
(Reglan®) reduces nausea/vomiting but not better pain control
Treatment of Acute Pain
IV fluids may benefit patients, although benefit is not well established Unlikely to be harmful especially in patients
with persistent GI symptoms Parenteral therapy preferred due to gastric
stasis & delayed absorption of oral medications
Treatment of Acute Pain
Droperidol (Inapsine®) probably most effective of dopamine agonists Pain relief at 2 hours approaching 100% Ideal dose – 2.5 mg IV FDA warning about QT prolongation
Treatment of Acute Pain
Prochlorperazine (Compazine®) 10 mg IV Effective with diphenhydramine (Benadryl®)
– 25 mg IV [Friedman 2008] Superior to SC sumatriptan in ED setting
[Kostic 2010] Children 0.15 mg/kg IV over 15 minutes
(max 10 mg) If EPS develop give diphenhydramine
1mg/kg (max 50 mg)
Treatment of Acute Pain
Metoclopramide* (Reglan®) IV – monotherapy 10 - 20 mg IV IM – 10 mg adjunct to other therapies
(SOR-C)
* FDA boxed warning 2/26/09 – Long-term or high-dose use of metoclopramide has been linked to tardive dyskinesia.
Treatment of Acute Pain Ergot alkaloids
Dihydroergotamine (D.H.E. 45®) – 1 mg IM/IV/SC Since it may cause nausea, more effective with
metoclopramide (Reglan®) to reduce nausea Nasal spray effective
Ergotamine/caffeine (1/100) (Cafergot®) Little evidence effective alone High risk of overuse & rebound headache
Treatment of Acute Pain Complementary medicine
Topical menthol 10% was more effective at complete pain relief than placebo at 2 hours (38.3% vs 12.1%) [Haghighi 2010] 10% solution of menthol crystals in ethanol Forehead and the temporal area most
painful are washed with tap water After drying 1 ml is applied with sponge on
a surface area of 5 x 5 cm Can be reapplied in 30 min
Treatment of Acute Pain - EBM
Patients with substantial disability will benefit from serotonin 5-HT1B/1D agonists (‘triptans’) SOR – A Clinical Evidence
http://www.clinicalevidence.com/ceweb/conditions/nud/1208/1208.jsp
Triptan Efficacy
No one triptan is superior in all pain relief parameters
Use one triptan for 2-3 attacks before abandoning that medication
If one does not work try another one
How is pain relief measured?
1) Was pain better within 2 hours?
2) Did the pain go away at 2 hours?
3) Did the pain stay away for at least 24 hours? (No immediate recurrence)
4) Did the patient consistently obtain pain relief from that medication?
Oral Triptan Efficacy
Was pain better within 2 hours? 55-65% of patients experience
improvement at 2 hours Can be repeated in 1 – 2 hours if partial
response
Oral Triptan Efficacy
Did pain go away within 2 hours? 25-35% of patients are pain free at 2 hours
Oral Triptan Efficacy
Did pain stay away for 24 hours? Freedom from pain at 2 hours, no rescue
medication, no recurrence of pain in 24 hours 20 - 25% of patients have sustained
freedom from pain
Oral Triptan Efficacy
Intra-patient Consistency? The same patient experiences pain relief
with the same medication Rizatriptan (Maxalt®) has highest intra-
patient consistency of the oral medications
Sumatriptan (Imitrex®) – Parenteral
6 mg SC Pain decreased within 2 hours - 76% Pain gone within 2 hours - 48% Consistent pain relief for that patient - 90% In ER best candidates are those with
previous response to this treatment Adverse events more frequent than with oral
medication And more intense
Sumatriptan (Imitrex®) – Parenteral
Cutaneous allodynia - sensation of pain in response to normally non-toxic touch stimuli (e.g. brushing hair, taking shower, putting hair in ponytail) Presence of cutaneous allodynia associated
with reduced response to SC sumatriptan Needle-free injection available (Sumavel®
DosePro™) Causes as much pain as needle & more
swelling, bruising & bleeding at site
22 yo female presents with throbbing headache, nausea, photophobia for 5 hours. BP 116/76, P 86. Which of these treatments would be appropriate for her?
Question
a. Ketorolac (Toradol®) 60 mg IM
b. Metoclopramide (Reglan®) 20 mg IV
c. Prochlorperazine (Compazine®) 10 mg IV
d. D.H.E. 45 1 mg IV
e. Sumatriptan (Imitrex®) 6 mg SQ
Triptans – Side Effects Tingling Paresthesias Warmth head, neck, chest & limbs Nasal spray associated with taste
disturbance
Triptans – Cautions Contraindicated with CAD, uncontrolled
hypertension or cerebrovascular disease, hemiplegic migraine
Should not be taken within 24 hrs of another triptan or ergotamine-containing/ergot-type medication
Taking them with an SSRI or SNRI can cause life-threatening serotonin syndrome
Combining Medications Sumatriptan 85 mg & Naproxen 500 mg
(Treximet®) more effective than either alone for acute pain relief
Unknown effect of taking 2 separate pills (not tested)
The combination may have some increased benefit in mild/moderate pain but no evidence of need for fixed dose combination (Medical Letter 2008)
Early Recurrence
Up to 75% of patients will experience a recurrence of pain within 48 hours Naproxen (500 mg) or sumatriptan (100 mg)
equally effective treating the recurrence [Friedman 2010]
Naproxen prophylactically can prevent recurrence (NNT – 3)
Triptans should not be used prophylacticly
Preventing Early Recurrence
Parenteral dexamethasone (10-25 mg IV) Produced 26% relative reduction in recurrence
within 72 hours [Colman 2008] Modest benefit in the ED – prevented 1 in 10
patients from experiencing moderate or severe recurrence [Singh 2008]
Later trials failed to find benefit with oral dexamethasone or prednisone
Acute Pain & Parenteral Opioids
Should not be used as 1st line therapy International Headache Consortium Canadian Association of Emergency
Physicians American Academy of Neurology
Meperidine (Demerol®) less effective than DHE and there is an: Increased risk of sedation Toxic metabolite with repetitive use
New Treatments Acute Pain Diclofenac oral solution (Cambia®) –
dissolve contents in water Sumatriptan patch (Zelrix™) – similar
levels to SC
New Treatments Acute Pain DHE inhaled (Levadex®) – patients not
responding to triptans or more than 6 hours into headache?
Calcitonin gene-related peptide (CGRP) antagonist (telcagepant) – as effective as zolmitriptan 5 mg oral
Single-pulse transcranial magnetic stimulation (sTMS) More effective than placebo in pain-free at 2
hours (39% vs 22%)
After the Migraine - Postdrome
Some patients may have: Mood changes “Hangover” Tired Weak Disoriented “Not right”
Chronic Migraine (CM) or Medication Overuse Headache (MOH)
Chronic migraine previously called ‘transformed migraine’
Consider medication overuse if ≥ 2 days/week for > 3 months analgesic use
Over period of time (months to years) can become almost daily headache Resembles mixture of tension & migraine Occasionally called ‘tension-vascular’ Hint – if awaken with headache consider
medication overuse
CM Modifiable Risk Factors
Risk factor associated with increased risk of developing CM Stressful life events Sleep disturbance (i.e. Snoring/sleep apnea) Obesity Baseline headache frequency Medication overuse
CM & MOH
Treatment Must stop acute medication to determine
Headaches will go away in a few days if medication overuse is etiology
No controlled trials of medication withdrawal May get severe withdrawal headache
Severe withdrawal headache can be treated with short course of prednisone
Randomized trial found no difference with steroid compared to placebo
Preventive Medication
Candidates: Unresponsive to acute attack medication &
disabling headache ≥ 2 attacks/month Increasing frequency of attacks Migraines with potential neurological
sequelae Patient preference (just wants to use
medication to prevent headaches)
Audience Question
23 y. o. female with recurrent migraine headaches. You advise starting preventive therapy. Which medication would be appropriate?
a) Anticonvulsant medication
b) Bipolar/anticonvulsant medication
c) Beta-blocker medication
d) Tricyclic medication
Prevention therapy - EBM First line treatment should be:
Propranolol (Inderal®) 20 – 240 mg/day
Timolol 10 – 30 mg/day Less evidence to support other beta-blockers
Amitriptyline 10 – 150 mg/day
Prevention therapy - EBM First line treatment should be:
Divalproex sodium (Depakote®) 125 – 500 mg BID
Topiramate (Topamax®) 50 - 100 mg BID May be as good as propranolol Anti-epileptic drugs had greater suicidal
ideation vs. placebo (0.43% vs 0.22%)
Prevention therapy
Second line (SOR-B) Gabapentin - pregnancy category D Carbamazepine* - pregnancy category D
* FDA Alert 12/12/07 – Dangerous or even fatal skin reactions can be caused by Carbamazepine therapy in patients with a particular HLA-B*1502 allele.
Prevention Therapies - EBM
Relaxation training (SOR-A) Progressive muscular relaxation Breathing exercises Directed imagery
Cognitive-behavioral (SOR-A) Combined with medication (SOR-B)
Acupuncture appears to be effective (SOR-A) Sham acupuncture just as effective as real
[Linde 2009] Thermal biofeedback with relaxation training
Audience Question
23 y. o. female with recurrent migraine headaches. You advise starting preventive therapy. Which medication would be appropriate?
a) Anticonvulsant medication
b) Bipolar/anticonvulsant medication
c) Beta-blocker medication
d) Tricyclic medication
Menstrual Migraine – two classes
A. Pure menstrual migraine without aura Migraine without aura on days -2 to +3
of cycle During at least 2 of 3 cycles
B. Menstrual related migraine without aura Migraine without aura as above and At other times of the month
Menstrual Migraine
Strongly associated with estrogen Steep drop in estrogen just prior to menses
may trigger headache Peak incidence is 1st day and preceding day
of cycle Other clinical features
Greater severity of pain Increased risk of nausea & vomiting Less responsive to acute treatment
Menstrual Migraine
Acute therapy the same as other migraines
Short-term prevention NSAID on days -7 to +6 helped
Naproxen sodium (Anaprox®) & mefenamic acid (Ponstel®) orally have been studied
Triptans starting day -2 for 5-6 days helped Frovatriptan (Frova®), naratriptan (Amerge®) &
sumatriptan (Imitrex®) orally have been studied
Prognosis of Migraines Study with 10 year follow-up of 11-14 year olds
at onset of migraines 40% no longer had headache 20% had episodic tension headache 20% had migraine type that was different from the
original diagnosed headache
Frequency & intensity usually decreases after menopause
Two fold increased risk of CVA [Spector 2010] May influence how aggressive to be with other
therapies to reduce risk of CVA
Tension Type Headache (TTH) - Criteria
First No vomiting – if vomiting probably a
migraine Not worsened by routine physical activity But can have one of these clinical
features Photophobia Phonophobia
TTH - Criteria
If no vomiting & only 1 other symptom - then need 2 of the following: Pressing, tightening or non-pulsatile pain Mild to moderate intensity of pain Bilateral No aggravation with movement
Diagnosis best made with use of headache diary for 4 weeks
TTH
Underlying cause uncertain Muscle tenderness & psychological
tension associated with aggravating them But are not clearly the cause
Susceptibility influenced by genetic factors
TTH
Gender ration female:male 5:4 Age of onset – 25-30 years old Peak prevalence – 30-39 years old Prevalence increases with higher
educational level
TTH – Treatment
OTC analgesic medications NSAID (prescription) May be augmented with:
Promethazine (Phenergan®) Diphenhydramine (Benadryl®) Metoclopramide (Reglan®)
Efficacy tends to decrease with increasing frequency of headaches
Cluster Headaches - Criteria Severe unilateral, bilateral, supraorbital or
temporal pain lasting 15-180 minutes (untreated) and one of following on same side Lacrimation Rhinorrhea Forehead or facial swelling Ptosis Miosis Eyelid edema
Cluster Headaches - Criteria Sense of restlessness (93% patients) or
agitation Prefer to be erect & move about
5 attacks with frequency of 1-8 on any given day from no other cause 75% of attacks last < 60 minutes
Cluster Headaches
Male : female – 2.1 : 1 Peak onset in 40’s 60% right sided Probably most severe pain known to
humans Female patients describe attacks as worse
than childbirth
Cluster Headache Treatment Acute
Sumatriptan 6 mg SC – relief in 15 min
Intranasal spray sumatriptan or zolmitriptan – relief in 30 min
Triptans limits on daily usage Limit to 2 SC or 3 nasal sprays per day to
prevent tachyphylaxis or rebound High flow O2 effective & safe [Cohen 2009]
O2 – 7 - 15 L/min with loose fitting nonrebreathing facial mask for 15 min
Cluster Headache Treatment Acute
DHE 0.5 - 1 mg IM or IV useful as abortive agent
Octreotide (Sandostatin®) 100 mcg SC can abort an attack NNT 5 for complete relief in 30 min
Prednisone 50-80 mg – short course
Cluster Headache Treatment
Prophylactic Verapamil 240-960 mg/day
Daily Headache When chronic daily headache is strictly
unilateral, same side, consider diagnosis to be: Hemicrania continua
Ipsilateral side one or more autonomic symptoms (ptosis, lacrimation, etc.)
Defined by absolute response to indomethacin (25 – 300 mg daily, must be continued indefinitely) If intolerant of indomethacin conside COX2
inhibitor
Key Points
Diagnosis of migraine headache is clinical Almost always positive family history
Triptans are preferred treatment for frequent migraines
Discuss preventive therapy with all patients
Provide treatment plan for breakthrough pain
What Questions do you have?