migraine headache – update on diagnosis & treatment herbert l. muncie, jr., m.d

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


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


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®)


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


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


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


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)


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


Did pain go away within 2 hours? 25-35% of patients are pain free at 2 hours


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


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?

migraine headache – update on diagnosis & treatment herbert l. muncie, jr., m.d

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