managing headache - rand swenson

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ManagingHeadache RandSwenson,D.C.,M.D.,Ph.D. ProfessorofNeurologyandAnatomy DartmouthMedicalSchool Hanover,NH General Headpainarisesfrompainsensitivestructures M i Meninges Bloodvessels Extracranial structures: Extracranialstructures: Sinuses Upper neck muscles, ligaments Upperneckmuscles,ligaments Eyes TMJ Dental Thebrainisnotsensitivetopain. General(cont.) Headpainconverges onSpinalNuc.of Trigeminal. Individualprojection neuronsrespondto stimulationofmany cranialstructures. 1

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Managing Headache by Rand Swenson, DC, MD, PhD

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Page 1: Managing Headache - Rand Swenson

Managing�Headacheg g

Rand�Swenson,�D.C.,�M.D.,�Ph.D.Professor�of�Neurology�and�Anatomy

Dartmouth�Medical�SchoolHanover,�NH

General• Head�pain�arises�from�pain�sensitive�structures

M i– Meninges

– Blood�vessels

Extracranial structures:– Extracranial�structures:• Sinuses

• Upper neck muscles, ligamentsUpper�neck�muscles,�ligaments

• Eyes

• TMJ

• Dental

– The�brain�is�not�sensitive�to�pain.

General�(cont.)� Head�pain�converges�on�Spinal�Nuc.�of�pTrigeminal.�

� Individual�projection�p jneurons�respond�to�stimulation�of�many�cranial�structures.

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Interaction�between�cervical�and�trigeminal�systems

� C2�nerve�terminates�in�spinal�nucleus�of�the�trigeminal�nerve

Sensitization of nociceptors

th h ldthreshold

allodyniay

hyperalgesia

vasodilation

Anatomy�of�cerebral�vascular�innervationinnervation

Girouard & Iadecola. J Appl Physiol 100: 328-335, 2006

General�(cont.)• Innervation�of�the�cerebral�blood�vessels.

• Trigeminal�nerve�is�sensory…– Substance�P,�calcitonin�gene�related�peptide,�neurokinin�A,�maybe�prostaglandins�and�nitric�oxide

– Trigemino�vascular system involved in neurogenic inflammationTrigemino vascular�system�involved�in�neurogenic�inflammation.• Unclear�what�activates�this�system..…

• Sympathetic�and�parasympathetic�innervation– Sympathetic�fibers�(norepi,�neuropeptide�Y,�prostaglandins),�parasympathetics�(acetylcholine,�neuropeptide�Y).

• Direct�innervation�from�serotonin�and�norepi�containing�nerve�fibers

N fib th i i it i id• Nerve�fibers�synthesizing�nitric�oxide

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General�(cont.)

• Serotonin�plays�a�role...– During�migraine�blood�5�HT�decreases,�urine�metabolites�iincrease

– Depletion�of�5�HT�triggers�attack– Intravenous 5�HT relieves attackIntravenous�5 HT�relieves�attack– Increased�activity�of�raphe�neurons�with�attacks– Sleep�decreases�activity�of�raphe�(and�stops�attack)– Decreased�5�HT�receptors�with�age

CentralCentral�sensitization

• Central�sensitization�and�neural�plasticity�d f l bdefinitely�contribute

• Pain�“memory”y• “Neurogenic�inflammation�is�clearly�a�part

Types�of�headacheyp�Common,�benign�headache�syndromes��Migraine

�Tension�Tension

�Cluster

�C i l�Cervical

�Post�traumatic

�Irritation�of�other�cranial�structures�(sinuses,�TMJ,�etc)

Types�of�headacheyp• Rarely,�HA�can�have�serious�causes�

– Eye�disorders– Brain�Tumor– Inflammation�of�blood�vessels– Intracranial hemorrhageIntracranial�hemorrhage

– Ischemic�cerebrovascular�diseaseI d/d d i t i l– Increased/decreased�intracranial�pressure• Pseudotumor�cerebri,�Chiari�malformation

/ h l–Meningitis/encephalitis

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A "Bad" StoryA� Bad �Story� Indicates�that�there�may be�a�serious�cause

� sudden�or�explosive�onset�of�headache.

� a�headache�that�is�always�in�the�same�place.

� a�headache�that�awakens�from�sound�sleep.

� a�headache�associated�with�weakness,�numbness,�vertigo,�loss�of�consciousness,�vision�loss

� changing�character�of�headache�in�an�older�patient.

� h d h i ld l i di id l� new�headache�in�an�elderly�individual.

� headache�associated�with�fever.

� headache in a person with a history of cancer� headache�in�a�person�with�a�history�of�cancer.

"Bad" SignsBad �Signs• Meningeal�irritation• Abnormal�vital�signs

– Malignant�hypertension,�fever• Papilledema�or�loss�of�venous�pulsations• Unequal pupils• Unequal�pupils• Visual�loss

b l• Abnormal�exam– Nystagmus,�dysconjugation,�ataxia,�asymmetry

Neuroimaging?Neuroimaging?

• Indications�to�consider�neuroimaging�include�the�g gfollowing:�unusual,�prolonged,�or�persistent�aura;�increasing�frequency,�severity,�or�change�in�clinical�f t fi t t i i b il f i lfeatures;�first�or�worst�migraine;�basilar;�confusional;�hemiplegic;�late�life�migraine�accompaniments;�aura�without headache; possibly headaches always on thewithout�headache;�possibly�headaches�always�on�the�same�side;�posttraumatic;�and�when�patient�or�family�and�friends�request.�

A�"good�story"g y• Long�history�of�headaches�of�a�similar�nature.• Slow�(not�explosive)�onset�of�headaches.• Headaches which are not always in the same placeHeadaches�which�are�not�always�in�the�same�place.�

• Not�loosing�function�during�the�attack�(no�focal�symptoms other than specific migraine symptoms)symptoms�other�than�specific�migraine�symptoms).

• No�systemic�symptoms�except�nausea.• Feeling�completely�normal�between�attacks.• Associated�symptoms�that�are�like�migraine.

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Types�of�headacheyp�Common,�benign�headache�syndromes��Migraine

�TensionMigraine and tension-

type headaches�Tension

�Cluster

�C i l

type headaches comprise the large�Cervical

�Post�traumatic

p gmajority of benign

h d h�Irritation�of�other�cranial�structures�(sinuses,�TMJ,�etc)

headaches

User�friendly�IHS�classification

� Divide�the�13�headings�into�two�categories� Primary headaches� Primary�headaches

�Migraine�with�or�without�aura�Migrainous�disorder� Tension�type headache (chronic or episodic)� Tension type�headache�(chronic�or�episodic)�Cervicogenic�headache�Cluster�headache�Post�traumatic�headache�Analgesic�rebound�headache�Mixed�headache�syndrome

� Secondary�headache�(headache�that�are�symptoms�of��organic�disease)disease)

Migraine�criteria�� IHS�1.1• Headache�with�at�least�two�of�the�following:

– Unilateral (one side) locationUnilateral�(one�side)�location

– Pulsing/pounding�quality

– Moderate�or�severe

– Aggravation�by�routine�physical�activity

• One of the following:One�of�the�following:– Nausea

– Light�and�sound�sensitivityg y

• Must�have�had�at�least�5�similar�headaches�in�the�pastpast

• It�must�not�be�due�to�other�disease

Migraine�� characteristicsg• Location�of�headache�

–Many�sites�• 44% only on one side of the head44%�only�on�one�side�of�the�head

• 22%�are�the�whole�head�14% th f h d• 14%�across�the�forehead�

• 13%�one�side�in�the�front�• 4%�across�the�back�of�the�head�• 2% one side in the back of the head2%�one�side�in�the�back�of�the�head�

• 1%�just�right�at�the�top�of�the�head 5

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Migraine�� symptoms�with�attacks

�Nausea�� 87%�Light�sensitivity�� 82%�Vomiting � 56%�Vomiting� 56%�Tender�scalp�� 65%�Diarrhea�� 16%�May�also�have:y�prior�"fluid�retention"��nasal "stuffiness" with attack�nasal� stuffiness �with�attack�mood�changes�common

Classic�migraine�� IHS�1.2• Migraine�accompanied�by�at�least�one�of�the�following:g– Visual

• Scintillating�scotomag• Fortification�spectra• Photopsia

– Sensory�• paresthesia• Numbness

– Other:• Unilateral�weakness• Aphasia�

Classic�migraine�� characteristics• Symptoms�� usually�5�30�minutes�before�HA

–Must start within 60 minutes of HA–Must�start�within�60�minutes�of�HA• Must�be�<�60�minutes�duration

– Spots�in�front�of�eyes�(often�colored�spots)�– Fortification�spectra��–Wavy�lines�in�vision– Flashing lightsFlashing�lights

– Tingling• Often “marches” over body• Often� marches �over�body

– Hemiplegia

Migraine activationMigraine�activation

Cao: Arch Neurol, Volume 56(5).May 1999.548-554 6

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Migranous�disorder�� not�fulfilling�other�i i (IHS 1 7)criteria�(IHS�1.7)

• Headaches�attacks�believed�to�be�migranous�that do not quite meet the diagnostic criteria forthat�do�not�quite�meet�the�diagnostic�criteria�for�any�of�the�forms�of�migraine

E l• Example:– Holocephalic�headache�of�a�non�pulsing�nature�with�nausea�and�photophobia�but�not�phonophobia

Tension�type�headache�� IHS�2.1� Headache�pain�accompanied�by�2�of�the�following:

h l� Pressing,�tightening�or�squeezing�quality�(nonpulsing)

� Bilateral�location� Not�aggravated�by�routine�physical�activity

� Headache�not�accompanied�by:� N d iti� Nausea�and�vomiting� Photophobia�and�phonophobia�(may�have�one)

� No�evidence�of�organic�diseaseg� Fewer�than�15�days�per�month�(episodic);�more�than�15�days�per�month�(chronic)

Muscle�contraction�headachestension�type�headaches

�Character:�Generalized,�nuchal/occipital,�bifrontal cap like or headband Typicallybifrontal,�cap�like�or�headband.��Typically�pressure�or�aching.

�Etiology:�May�be�perpetuated�or�caused�by�neck�pathology.p gy

Migraine�vs.�Tensiong� Age:�onset�<20�years�� 55%�migraine�and�30%�tension

�W i t i 60% f i i d 10% f�Warning:�symptoms�in�60%�of�migraines�and�10%�of�tension

l f d f� Daily:�in�3%�of�migraines�and�50%�of�tension

� Unilateral:�in�80%�migraine�and�10%�tension

� Throbbing:�in�80%�of�migraine�and�30%�of�tension

� Vomiting:�in�50%�of�migraine�and�10%�of�tensiong g

� Family�History:�in�65%�of�migraine�and�40%�of�tension

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Migraine�vs.�Tension�Headache

�Similarities:�Migraine may progress to tension headache�Migraine�may�progress�to�tension�headache

�Migraine�and�tension�similar�in�that:��Neck�muscle�contraction�found�in�both

�Neck�muscle�contraction�and�pain�common�in�prodrome�of�both

� Cephalic�hyperemia�attends�HA�in�both

� Increased�prevalence�of�epilepsy�in�both

� Low�platelet�serotonin�occurs�in�both

� Psychological profiles of patients indistinguishable� Psychological�profiles�of�patients��indistinguishable

� Both�disorders�respond�to�similar�medicines�(Elavil,�ergonovine�and�inderal)

Migraine�often�progresses�to�g p gtension�type�headache

“Per headache” treatmentPer�headache �treatment

• How most patients manage their HA• How�most�patients�manage�their�HA• “Step�care”

– Escalating�levels�of�treatment– Relaxation– Herbal– PhysicalPhysical

– Analgesics• Earlier is better• Earlier�is�better

“Per headache” treatmentPer�headache �treatment

• 81% of migraine patients take81%�of��migraine�patients�take�medication

• Only�32%�are�using�prescription medicationprescription�medication

• 60%�take�over�the�counter�medication

Migraine Sufferer Identification and Impact Migraine Sufferer Identification and Impact --onon--life Studylife Study

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“Per�headache”�treatment�Potential�problems�with�step�care�Analgesic rebound is a common condition in�Analgesic�rebound�is�a�common�condition�in�patients�with�frequent�headache�Especially with narcotics butalbital acetaminophen�Especially�with�narcotics,�butalbital,�acetaminophen�and�caffeine�containing�combinations

�Many medications have unpleasant side effects�Many�medications�have�unpleasant�side�effects�GI�effects�� NSAID

d b lb l�Sedation�� narcotics,�butalbital,�antiemetics�Triptans � chest�pain/tightness,�rare�MI

“Analgesic rebound” headacheAnalgesic�rebound �headache� Usually�daily,�diffuse�and�bilateral�with�superimposed�

i i i di llmigraines�periodically

� Physical�and�mental�exertion�worsens

� Often�with�HA�in�AM�or�awaken�with�it

� High�coincidence�of�restlessness,�nausea,�forgetfulness,�asthenia,�depression

� Tolerance�to�abortive�medication

� No�response�to�preventative�migraine�medication

Mathew NT. Neurol Clin NA 1990;8:903Mathew NT. Neurol Clin NA 1990;8:903--912912

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Frequency of misdiagnosisFrequency�of�misdiagnosis

• Only�56%�of�migraineurs�know�that�they�have�migraine.�In�a�recent�study,�y g y g y,sinus�headache�(39%),�tension�type�headache�(31%),�and�stress�headache�(29%)�were�common�self�reported�diagnoses�among�migraineurs (subjects could list more than one probable diagnosis).migraineurs�(subjects�could�list�more�than�one�probable�diagnosis).

– Diamond S., Bigal M.E., Silberstein S., et al: Patterns of diagnosis and acute and preventive treatment for migraine in the United States: results from the American Migraine Prevalence and Prevention study. Headache 47. 355-363.2007

• In�a�study�of�2991�patients�who�had�a�history�of�self�described�or�f fphysician�diagnosed�sinus�headache,�88%�were�diagnosed�as�fulfilling�

migraine�(80%�of�patients)�or�migrainous�criteria�(8%�of�patients)– Schreiber�C.P., Hutchinson�S., Webster�C.J., et�al: Prevalence�of�migraine�in�patients�with�a�history�of�self�reported�or�

physician�diagnosed “sinus” headache Arch Intern Med 164 1769�1772 2004physician diagnosed� sinus �headache.� Arch�Intern�Med 164. 1769 1772,�2004

Migraine is expensiveMigraine�is�expensive

�Average costs in 18 months�Average�costs�in�18�months�$2,187�in�medical�bills�For�doctors�visits,�emergency�room�visits,�hospitalizationsp

�$371�in�bill�for�drugs�

�$2 558 l bill�$2,558�total�bill

Clouse & Osterhaus. Ann Pharmacother 1994;28:659-664

Migraine impactMigraine�impact

� E i d ti it� Economic�productivity� 89%�of�migraine�suffers�worked�at�half�or�less�of�their�usual�productivity for an average of 6 days a monthproductivity�for�an�average�of��6�days�a�month�

� 56%�missed�work�at�an�average�rate�of�2.2�days�a�month�

� Estimated lost labor costs (per month)� Estimated�lost�labor�costs�(per�month)� $572�per�working�male�and�

� $300 per working female� $300�per�working�female

Osterhaus et al. Pharmacoeconomics 1992;2:67-76

Lost�productivity• Stewart�and�colleagues�mailed�a�questionnaire�to�193,477�participants�in�the�American�Migraine�P l d P ti t dPrevalence�and�Prevention�study.�

• The�average�lost�Productive�Time�(LPT)�was�1.8�hours�for�headache and 2 8 for all health�related causesheadache�and�2.8�for�all�health�related�causes

• 76.5%�of�the�headache�related�LPT�was�explained�by�reduced performance (ie, presenteeism).reduced�performance�(ie,�presenteeism).�

• The�29%�of�migraine�cases�with�11+�headache�d/mo�accounted�for�49%�of�overall�LPT;�the�19%�of�those�with�pain�score�of�9�to�10�on�a�0�to�10�scale�accounted�for�33%�of�the�overall�LPT.

Stewart WF Wood G C Razzaghi H et al: Work impact of migraine– Stewart�W.F., Wood�G.C., Razzaghi�H., et�al: Work�impact�of�migraine�headaches.� J Occup�Environ�Med 50. (7):�736�745.2008

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Difficult�HA�and�Migraine�is�an�opportunity

• Underserved�population

• Underdiagnosed�population

• A�population�for�which�conventional�medical�Tx�is�ineffective�or�even�counterproductive

• A�population�that�most�physicians�don’t�want�to�see�and/or�are�inadequately�prepared�to�see

• Analgesic�rebound�or�analgesic�overuse�headache�is�common

• Oral�medicine�often�not�effective�during�attack

Steps�in�migraine�treatment

� Diagnosis

� Establish�good�doctor�patient�relationship

� Educate�patients�and�familiesp

� Reassure�patients

� Ask patients to keep daily log of HA� Ask�patients�to�keep�daily�log�of�HA

� Explore�non�pharmacologic�treatments

� Treat aggressively until adequate response� Treat�aggressively�until�adequate�response

� Periodically�re�evaluate�treatment

Migraine�treatmentg• Modification�of�trigger�factors

• Stress�management

• Sleep�hygiene

• "Per�headache"�treatment?

• Prophylactic�therapyp y py– Spinal�manipulation

– ?Acupuncture

– Omega�3�oils,�antioxidents,�magnesium,�B�vits,�herbal

• Behavioral�therapypy

Migraine � PrecipitantsMigraine� Precipitants• Stress�important…

– but�often�in�"let�down"�period..

• Pregnancy�� may�get�better�or�worse

• Low�dose�OC's�– Better�than�high�dose,�still�risky

• 60%�linked�to�menstruation,�14%�exclusively

• Common�factors:�lack�of�sleep,�hunger,�head�trauma,�excessive�sleep,�altitude,�high�vitamin�A,�drugs,�cold�food,�eye�strain,�odors�(perfume,�smoke),�fluorescent�lights,�allergies,�glare.

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Migraine�� Precipitants�(cont.)

• Common�foods:�Chocolate�(50%),�alcohol/wine�(40%),�dairy�products�(30%),�citrus�(30%),�Beer�(15%),�fried�foods�(10%),�pork�(10%),�onions�(9%),�t / ff (7%) f d (5%)tea/coffee�(7%),�seafood�(5%).

• Occasionally,�salt,�aspartame,�nitrates.�• Caffeine�withdrawal.�

Sleep�Disorders

�Overnight�headaches�or�headaches�upon�arising�reflected sleep disturbance in 55% of patientsreflected�sleep�disturbance�in�55%�of�patients.

�Treatment�of�sleep�disorder�improved�headache�in�all�of�this�55%�(and�stopped�it�in�65%).� Penzien�DB.�Rains�JC.�Andrasik�F.�Behavioral�management�of�recurrent�h d h th d d f i d i i i A li dheadache:�three�decades�of�experience�and�empiricism.�Applied�Psychophysiology�&�Biofeedback.�27(2):163�81,�2002.

Neck and TMJ contributes to HANeck�and�TMJ�contributes�to�HA

• May�be�associated�with�temporomandibular�joint�y p jpathology�and�upper�cervical

• Occipital�neuralgia:�may�be�from�direct�injury�or�from�p g y j yspasm�of�trapezius�and�semispinalis�muscles.��– Produces�an�ipsilateral�aching,�burning�or�shooting�pain.��p g, g g pOccasionally�with�electrical�or�lightning�sensations�in�occiput

• Convergence�in�spinal�nucleus�of�the�trigeminal

Cervicogenic headacheCervicogenic headache� Strong�attachments�to�the�duramatter in the C1�Occiput levelmatter�in�the�C1�Occiput�level

� Interaction�with�C2�nerve�root

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Rectus capitus posterior minorRectus�capitus�posterior�minor� This�has�strong�dural�attachments�in�the�C1�Occiput�level

Dural attachmentsDural�attachments

Dural�attachmentsattachments

Prophylaxisop y a s

• This is especially useful if headaches areThis�is�especially�useful�if�headaches�are�frequentU ll 2 4 i d th– Usually�2�4�severe�episodes�per�month

– Especially�if�HA�medication�2�or�more�days/wk• Chiropractic�treatment�was�comparable�(and�much�longer�lasting)�than�a�common�migraine�g g) gprophylactic�medication.

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Migraine�and�Manipulation� Nelson,�et�al.�JMPT�21:511�519,�1998

� Spinal�manipulation�versus�amitriptyline�and�the�combination�of�p p p yboth�for�the�prophylaxis�of�migraine.

� Prospective,�randomized�parallel�group�comparison.� 4�week�baseline,�8�weeks�of�treatment�and�4�week�f/u

� 218�patients�with�migraine.�Used�headache�index�score�from�daily�headache�diary.

� Reduction�in�headache�score�of�49%�for�amitriptyline�40%�for�manipulation�and�41%�for�combination.� In�the�4�week�post�treatment�period,�reduction�from�baseline�was�24%�for�amitriptyline,�42%�for�chiro�and�25%�for�both.

Migraine�and�Manipulation

� PARTICIPANTS:�175�patients�with�migraine�(>1/mo)�� INTERVENTIONS:�2�mo.,�16�TX�max.�� RESULTS:�treatment�group�(n=83)�showed�statistically�

f f (significant�improvement�in�migraine�frequency�(P�<�.005),�duration�(P�<�.01),�disability�(P�<�.05),�and�medication use (P< 001)medication�use�(P<�.001)

� 22%�of�treated�patients�had�>�90%�reduction�

Tuchin PJ. Et al JMPT. 23:91-5

Tension�Type�HAyp• 126�patients�� >3�months�with�at�least�1�episode�per�week�of�tension�type�headache.�Randomized�to�group�1�(spinal�manipulation,�moist�heat�and�OTC's)�or�group�2�(amitriptyline�and�OTC's�as�needed).��There�was�no�pretreatment�difference�in�headache frequency intensity OTC use or functional statusheadache�frequency,�intensity,�OTC�use�or�functional�status.

• Treatment�� Group�1�was�treated�twice�per�week�for�6�weeks,�group 2 was seen a baseline and 6 weeks later.group�2�was�seen�a�baseline�and�6�weeks�later.

• Results�� 4�weeks�after treatment�group�1�had�>30%�improvement�in�intensity,�frequency�and�OTC�use�and�16%�improvement�in�y q y pfunctional�status.��Group�2�improved�<6%�in�all�measures.�

Boline et al.

Indications�for�preventive�TX• Indications�for�preventive�treatment�are�as�follows:

– Headaches�significantly�interfere�with�the�patient's�daily�routine�despite�acute�treatment;�

– Acute�medications�are�contraindicated,�ineffective,�or�overused or have intolerable side effects;overused,�or�have�intolerable�side�effects;�

– Frequent�migraines�(two�or�more�attacks�a�week);�– Uncommon migraine types (hemiplegic basilarUncommon�migraine�types�(hemiplegic,�basilar,�prolonged�aura,�or�migrainous�infarction);�

– Cost�of�acute�medications�is�significantly�greater�than�the�cost�of�preventive�medication;�

– Patient�preference.

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HA�Prophylaxisp y� Decision�to�use�preventative�medicines is�based�on�severity frequency and the availability of effectiveseverity,�frequency�and�the�availability�of�effective�treatments

� Common medicines used for this purpose include:� Common�medicines�used�for�this�purpose�include:� Heterocyclic�antidepressants� Beta�blockers� Calcium�channel�blockers� Seizure�medicines:�Valproate,�Topiramate,�Neurontin,�etc

Principles�of�preventive�TX• Start�with�a�low�dose�and�increase�it�slowly,�depending�on�the�response�and�side�effects.

• Each�treatment�should�be�given�a�trial�of�2�to�3�months at�adequate�doses.

• Overused medications should be discontinued or tapered• Overused�medications�should�be�discontinued�or�tapered�(depending�on�the�drug).�They�may�be�causing�rebound�headache�and�can�decrease�efficacy�of�preventive�treatment

• The�patient�should�keep�a�HA�diary�to�monitor�his�or�her�HA.• The�clinician�should�educate the�patient�about�the�rationale�for�treatment and possible side effects and should address the patient'streatment�and�possible�side�effects�and�should�address�the�patient s�expectations�for�treatment.�Many�patients�want�a�complete�cure,�and�although�this�is�certainly�understandable,�it�is�usually�not�possiblepossible.

When�to�stop�preventive�TX?• Only�RCT�trial�has�been�performed�to�investigate�migraine�after�preventive�treatment�discontinued.�– Patients�treated�with�topiramate�for�6�months�were�randomized�to�continue�or�switch�to�placebo�for�6�months.

– Discontinuation “ was associated with persistent benefits– Discontinuation� …was�associated�with�persistent�benefits�compared�with�values�before�treatment,�although�numbers�of�migraine�days�were�higher�and�quality�of�life�was�lower�in�ti t h di ti d t i t th i th hpatients�who�discontinued�topiramate�use�than�in�those�who�

continued�treatment.�Patients�should�therefore�be�treated�for�6�months,�with�the�option�to�continue�treatment�to�12�months�in�some�patients,�particularly�those�whose�migraine�frequency�decreased�substantially�with�topiramate.”

• Diener�H.C., Agosti�R., Allais�G., et�al: Cessation�versus�continuation�of��6�month�migraine�preventive�therap ith topiramate (PROMPT) a randomised do ble blind placebo controlled trial Lancettherapy�with�topiramate�(PROMPT):�a�randomised,�double�blind,�placebo�controlled�trial.� Lancet�Neurol 6. 1054�1062,�2007

Magnesium• 81�migraineurs�(3.6�attacks/mo.)�

– Baseline=4�weeks;�randomized�to�600�mg�(24�mmol)�Mg2+; g ( ) g(trimagnesium dicitrate)�daily�for�12�weeks�or�placebo

– In�weeks�9�12,�attack�frequency�was�reduced�41.6%�in�the�Mg2+ group and 15 8% in the placebo group (compared to theMg2+ group�and�15.8%�in�the�placebo�group�(compared�to�the�baseline;�p�<�0.05)

– Days�with�migraine and�drug�consumption�also�decreased�gsignificantly�w/�Mg2+

– Duration�and�intensity�of�the�attacks�and�the�drug�consumption per attack tended to decrease (N/S)consumption�per�attack�tended�to�decrease�(N/S)

• Diarrhea�(18.6%);�gastric�irritation�(4.7%)

Peikert, eta al. Cephalalgia. 16(4):257-63, 1996

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Magnesium

40 i i h i i i h• 40�patients�with�migraine�without�aura

• 600�mg/day�of�oral�magnesium�citrate�per�day�versus�placebo�

• Significant�decrease�in�migraine�attack�frequency�and�severity.�– Koseoglu�et�al.�The�effects�of�magnesium�prophylaxis�in�migraine�without�aura.�Mag�Res.�2008;21:101–108

Magnesium• 69�patients�(2�6�common�migraines/mo�for�>2�years)• Randomized to 10 mmolMg2+ bid or placeboRandomized�to�10�mmol�Mg bid�or�placebo�• 4�week�baseline�period;�12�weeks�of�Tx�• 10 responders (>50% fewer HA) in each group (28 6%10�responders�(>50%�fewer�HA)�in�each�group�(28.6%�w/TX;�29.4%�w/�placebo)– 45.7%�of�patients�in�the�magnesium group�reported�mild�adverse�events�like�diarrhea�(23.5%�w/�placebo).

• Study�stopped�early�D/T�no�effect,�but�poorly�absorbed�form ofMg2+form�of�Mg2+

Pfaffenrath, et al. Cephalalgia. 16(6):436-40, 1996

Magnesium• 86�children�(3�to�17)�

– 4�week history of at least weekly moderate�to�severe– 4�week�history�of�at�least�weekly,�moderate�to�severe�migraine�

• Randomized�to�magnesium oxide�(9�mg/kg�per�day�by�g ( g g p y ymouth�divided�3�times�a�day�with�food)�or�placebo�for�16�weeks

f d f h ( )• Significant�decrease�in�HA�frequency�with�Tx�(P�=.0037)�but�not�placebo�(P�=.086)

• Magnesium oxide group had significantly lower• Magnesium oxide�group�had�significantly�lower�headache�severity�(P�=.0029)

Wang, et al. Headache. 2003 Jun; 43(6): 601-10

Mitochondria• Mitochondrial�dysfunction�has�been�speculated�to�play�a�role�in�migraine�pathophysiology

• Koo�et�al.�Mitochondrial�encephalomyopathy,�lactic�acidosis,�stroke�like�episodes�(MELAS):�Clinical,�radiological,�pathological,�and�genetic�observations.�Ann�Neurol.�1993;34:25–32.

• Lanteri�Minet�&�Desnuelle.�Migraine�and�mitochondrial�dysfunction.�Rev�Neurol.�1996;152:234–238.

Mi i h d d it h d i l h h l ti t ti l• Migraineurs�have�reduced�mitochondrial�phosphorylation�potential�in�between�headaches

• Montagna�et�al.�31P�magnetic�resonance�spectroscopy�in�migraine�without�aura.�Neurology.�1994 44 666 6691994;44:666–669.

• Bresolin�et�al.�Muscle�mitochondrial�DNA�deletion�and�31P�NMR�spectroscopy�alterations�in�a�migraine�patient.�J�Neurol.�1991;104:182–189.

• This might reduce the threshold for migraine attacks Rationale for• This�might�reduce�the�threshold�for�migraine�attacks.�Rationale�for�supplements�that�enhance�mitochondria– Riboflavin,�CoQ10,�and�alpha�lipoic�acid.

• Sparaco�et�al.�Mitochondrial�dysfunction�and�migraine:�Evidence�and�hypotheses.�Cephalalgia.�2006;26:361–372.

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Riboflavin• Riboflavin,�also�known�as�vitamin�B2,�is�a�precursor�for�flavin�mononucleotides�that�are�cofactors�in�the�Krebs�cycle It is essential for membrane stability and thecycle.�It�is�essential�for�membrane�stability�and�the�maintenance�of�energy�related�cellular�functions.

• One well�designed RCT evaluating the use of riboflavin as aOne�well designed�RCT�evaluating�the�use�of�riboflavin�as�a�migraine�prophylactic�agent.�

• Daily�use�of�400�mg�riboflavin�for�3�months�resulted�in�a�50%�reduction�in�attacks�in�59%�of�patients,�as�compared�with�15%�for�placebo.�

d d h d l• Two�minor�adverse�reactions,�diarrhea�and�polyuria,�were�reported�in�the�treatment�group.

• Schoenen J Jacquy J Lanaerts M Effectiveness of high�dose riboflavin in migraineSchoenen�J,�Jacquy�J,�Lanaerts�M.�Effectiveness�of�high dose�riboflavin�in�migraine�prophylaxis.�Neurology.�1998;50:466–470.

Riboflavin• A�recent�pharmacogenetic�study�demonstrated�that�riboflavin may be more effective in the treatment ofriboflavin�may�be�more�effective�in�the�treatment�of�migraine�patients�with�non�H�mitochondrial�DNA�haplotypes.haplotypes.�

• Riboflavin�is�effective�in�deficiencies�of�the�electron�transport chain complex I but not in isolated complex IVtransport�chain�complex�I�but�not�in�isolated�complex�IV�deficiency– This haplotype is more common in Northern EuropeansThis�haplotype�is�more�common�in�Northern�Europeans

• DiLorenzo,�et�al.�Mitochondrial�DNA�haplogroups�influence�the�therapeutic�response�to�riboflavin�in�migraineurs.�Neurology.�2009 72 1588 15942009;72:1588–1594.

CoQ10• CoQ10�is�an�endogenous�enzyme�cofactor�made�by�all�cells�in�the�body,�functioning�to�

promote�mitochondrial�proton�electron�translocation.�• An�open�label�study�of�31�patients�with�migraine�used�150�mg�daily�of�CoQ10�for�3�

months,�61%�had�at�least�a�50%�reduction�in�migraine�days�without�significant�adverse�events.

– Rozen�TD,�Oshinsky�ML,�Gebeline�CA,�et�al.�Open�label�trial�of�Coenzyme�Q10�as�a�migraine�preventive.�Cephalalgia.�2002;22:137–141.

• A�small�randomized�controlled�trial�was�conducted�in�which�the�treatment�group�received�100�mg�of�CoQ10�3�times�daily.�

• CoQ10�significantly�decreased�attack�frequency,�headache�days,�and�days�with�nausea.

– Sandor�PS,�DiClemente�L,�Coppola�G,�et�al.�Efficacy�of�coenzyme�Q10�in�migraine�prophylaxis:�a�randomized�controlled�trial.�Neurology.�2005;64:713–715.

• CoQ10�levels�were�measured�in�a�study�of�1550�pediatric�patients�(mean�age�13 3 3 5 ) i h f h d h d f d b b l h f i13.3±3.5�y)�with�frequent�headaches,�and�found�to�be�below�the�reference�range�in�32.9%.�

• Supplementation�with�1�to�3�mg/kg/d�of�CoQ10�in�liquid�gel�capsule�formulation�resulted in an improvement in total CoQ10 levels headache frequency and degree ofresulted�in�an�improvement�in�total�CoQ10�levels,�headache�frequency�and�degree�of�headache�disability.

– Hershey�AD,�Powers�SW,�Vockell�AB,�et�al.�Coenzyme�Q10�deficiency�and�response�to�supplementation�in�pediatric�and�adolescent�migraine.�Headache.�2007;47:73–80.

Coenzyme�Q10• CoQ10 (3�x�100�mg/day)�v.�placebo�• 42migraine patients42�migraine patients• Double�blind,�randomized,�placebo�controlled�trial

• CoQ10 was superior to placebo for attack frequency• CoQ10 was�superior�to�placebo�for�attack�frequency,�headache�days�and�days�with�nausea�in�the�third�treatment month and well toleratedtreatment�month�and�well�tolerated– 50%�responder�rate�for�attack�frequency�was�14.4%�for�placebo�and�47.6%�for�CoQ10

Sandor, et al. Neurology 64(4):713-5, 2005

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Alpha�lipoic�acid• Alpha�lipoic�acid�(also�known�as�thioctic�acid)�enhances�mitochondrial�oxygen�metabolism�and�ATP�production.

• One�placebo�controlled�RCT�

• Fifty�four�patients�received�either�600�mg�alpha�lipoic�acid�or�placebo daily for 3 monthsplacebo�daily�for�3�months.�

• Although�there�was�a�clear�trend�for�reduction�of�migraine�frequency�after�treatment�with�alpha�lipoic�acid,�the�result�was�q y p p ,not�significant.�

• This�result�was�attributed�to�the�fact�that�the�study�was�underpowered.�However,�within�group�analyses�did�show�a�significant�reduction�in�attack�frequency,�headache�days,�and�headache severity in the treatment group.headache�severity�in�the�treatment�group.

– Magis�D,�Ambrosini�A,�Sandor�P,�et�al.�A�randomized�double�blind�placebo�controlled�trial�of�thioctic�acid�in�migraine�prophylaxis.�Headache.�2007;47:52–57.

Fatty�acids• Eicosapentaenoic�acid�(EPA),�may�also�be�useful�in�the�prevention�of�headaches.�Small�studies�suggest�that�HA�severity�&�frequency�

b d d b ddi di t EPA ibl l ican�be�reduced�by�adding�dietary�EPA,�possibly�lowering�prostaglandin�levels�and�serotonin�activity.�

– Werbach�M.�Nutritional�Influence�on�Illness:�A�Sourcebook�of�Clinical�R h T CA Thi d Li P I 1988Research.�Tarzana,�CA:�Third�Line�Press,�Inc;�1988.

• Omega�3�fatty�acid�supplementation�also�associated�with�a�positive�outcome�in�the�treatment�of�mood�disorders.

– Stahl�LA,�Begg�DP,�Weisinger�RS,�et�al.�The�role�of�omega�3�fatty�acids�in�mood�disorders.�Curr�Opin�Investig�Drugs.�2008;1:57–64.�

• Although the FDA has not established a recommended dailyAlthough�the�FDA�has�not�established�a�recommended�daily�allowance�for�EPA,�a�dose�of�600�mg/d�in�3�divided�doses�has�been�suggested�for�headache�prevention.

Dupois S A comprehensive approach to treatment of intractable headaches– Dupois�S.�A�comprehensive�approach�to�treatment�of�intractable�headaches.�Townsend�Lett�Doctors.�1990;88:740–744.

Fatty�acids• Eicosapentaenoic�acid�(EPA),�may�also�be�useful�in�the�prevention�of�headaches.�Small�studies�have�suggested�that�headache�

i d f b d d b ddi EPA h diseverity�and�frequency�can�be�reduced�by�adding�EPA�to�the�diet,�possibly�by�lowering�prostaglandin�levels�and�serotonin�activity.�– Werbach�M.�Nutritional�Influence�on�Illness:�A�Sourcebook�of�Clinical�Research.�Tarzana,�CA:�Third�Line�Press,�Inc;�1988.

• Omega�3�fatty�acid�supplementation�has�also�been�associated�with a positive outcome in the treatment of mood disorderswith�a�positive�outcome�in�the�treatment�of�mood�disorders.– Stahl�LA,�Begg�DP,�Weisinger�RS,�et�al.�The�role�of�omega�3�fatty�acids�in�mood�disorders.�Curr�Opin�Investig�Drugs.�2008;1:57–64.�

Al h h h FDA h bli h d d d d il• Although�the�FDA�has�not�established�a�recommended�daily�allowance�for�EPA,�a�dose�of�600�mg/d�in�3�divided�doses�has�been�suggested�for�headache�prevention.– Dupois�S.�A�comprehensive�approach�to�treatment�of�intractable�headaches.�Townsend�Lett�Doctors.�1990;88:740–744.

Butterbur

• Petasites�is�thought�to�act�through�calcium�channel�regulation�and inhibition of peptide leukotriene biosynthesis Leukotrienesand�inhibition�of�peptide�leukotriene�biosynthesis.�Leukotrienes�and�other�inflammatory�mediators�may�have�a�role�in�the�inflammatory�cascade�associated�with�migraine.�

• Although�the�butterbur�plant�itself�contains�pyrrolizidine�alkaloids�which�are�hepatotoxic�and�carcinogenic,�these�compounds�are�removed�in�the�commercially�available�p ypreparations.�[Petadolex]

• Placebo�controlled�RCT�using�50�mg�of�butterbur�twice�daily,�showed a significantly reduced number of migraine attacks andshowed�a�significantly�reduced�number�of�migraine�attacks�and�migraine�days�per�month.�

– Grossman�M,�Schmidrams�H.�An�extract�of�Petasites�hybridus�is�effective�in�the�prophylaxis�of�migraine.�Int�J�Clin�Pharmacol�Ther.�2000;38:430–435.

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Petasites�(butterbur)• Three�arm,�parallel�group,�randomized�trial�

– Petasites�extract�75�mg�and�50�mg�bid,�or�placebo�in�245�patients�with�migraine

h f i i k• Over�4�months�of�treatment,�migraine attack�frequency�was�reduced�by�48%�for�Petasites�extract�75 mg bid (p = 0 0012 vs placebo) 36% for Petasites75�mg�bid�(p�=�0.0012�vs�placebo),�36%�for�Petasites�extract�50�mg�bid�(p�=�0.127�vs�placebo),�and�26%�for�the placebo groupthe�placebo�group

• Potential�carcinogen• Lipton et al Neurology 63(12):2240-4 2004Lipton,�et�al.�Neurology. 63(12):2240 4, 2004

Petasites�(butterbur)� 4�week�baseline�phase� 33 patients randomized to Tx (50 mg butterbur twice� 33�patients�randomized�to�Tx�(50�mg�butterbur twice�a�day)�or�placebo�(n=27)

�Mean attack frequency per month decreased from 3 4�Mean�attack�frequency�per�month�decreased�from�3.4�at�baseline�to�1.8�after�3�months�(p�=�0.0024)�with�TX�and�from�2.9�to�2.6�with�placebo�group�(n.s.).�

� >�or�=50%�improvement:�45%�in�the�Tx�group�and�15%�in�the�placebo�group.�

� Butterbur was�well�tolerated.

Diener, et al. European Neurology 51(2):89-97, 2004

Butterbur

• A�multicenter�prospective�open�label�study�94�of�butterbur in 109 children and adolescents withbutterbur�in�109�children�and�adolescents�with�migraine�resulted�in�77%�of�all�patients�reporting�a�reduction�in�migraine�frequency�of�at�least�50%.�

– Pothmann�R,�Danesch�U.�Migraine�prevention�in�children�and�adolescents:�results�of�an�open�study�with�a�special�butterbur�root�extract.�Headache.�2005;45:196–203.

• Butterbur�is�well�tolerated�and�no�serious�adverse�events�occurred.�The�most�frequently�reported�adverse�reactions�were�mild�gastrointestinal�events,�predominantly eructation (burping)predominantly�eructation�(burping).

Feverfew� The�use�of�feverfew�(Tanacetum�parthenium)�for�migraine�prophylaxis�was�assessed�in�a�randomised,�double�blind,�l b t ll d t dplacebo�controlled�crossover�study.�� 72�volunteers�were�randomly�allocated�to�receive�either�one�capsule�of�dried�feverfew�leaves�a�day�or�matching�placebo�for�four�months�and�then�transferred�to�the�other�treatment�limb�for�a�further�four�months.�

� There�was�a�reduction�in�the�mean�number�and�severity�of�yattacks�in�each�two�month�period,�and�in�the�degree�of�vomiting;�duration�of�individual�attacks�was�unaltered.�There were no serious side�effectsThere�were�no�serious�side�effects.� Murphy�et�al.�Lancet.��2(8604):189�92,�1988�Jul�23.

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Feverfew• RCT�of�extract�of�feverfew (MIG�99,�6.25�mg�t.i.d.)�vs.�placebo

• 170�migraineurs;�4�week�baseline;�treated�for�16�weeks�

• Migraine frequency�decreased�by�1.9/mo�(from�4.76)�in�months�2�&�3�with�Tx�(decreased�by�1.3�w/placebo)�(P=0.0456)

• No�evidence�of�more�adverse�effects�compared�to�placebo– Diener�HC,�Pfaffenrath�V,�Schnitker�J,�et�al.�Efficacy�and�safety�of�6.25�mg�tid�feverfew�CO2�extract�(MIG�99)�in�migrane�prevention—a�randomized,�double�blind,�multicenter,�placebo�controlled�study.�Cephalalgia.�2005;25:1031–1041.

– Pfaffenrath,�et�al.(Cephalalgia.�22(7):523�32,�2002)�believe�this�may�only�work�in�patients�with�frequent�migraine�(4�or�more/mo)

Combinations• RCT�of�riboflavin�400�mg/mg�300�mg/feverfew�100�mg�v.�placebo�(25�mg�riboflavin)�

• 49 migraineurs: 1�month�run�in;�3�month�trial• No�difference�between�active�and�"placebo"�groups

– 42%�of�Tx�and�44%�of�placebo�achieved�>50%�reduction�(no�difference).– No�significant�difference�in�change�in�mean�number�of�migraines,�

migraine days,�migraine index,�or�medication�doses• Both�groups�had�significant�reduction�(from�baseline)�in�number�of�migraines,�migraine days,�and�migraine index.�Thi ff t d i l b t• This�effect�exceeds�prior�placebo�reports

Maizels, et al. Headache. 44(9):885-90, 2004

5�Hydroxytryptophan� 48�elementary�and�junior�high�school�students�with�recurring headache and sleep disorders were selectedrecurring�headache�and�sleep�disorders�were�selected�for�this�study.�

� A double blind cross over trial with placebo� A�double�blind,�cross�over�trial�with�placebo�confirmed�benefit�of�L� 5�hydroxytryptophan�for�headache and some sleep disorders in particularheadache�and�some�sleep�disorders,�in�particular�frequent�awakenings�and�some�parasomnias.� De�Giorgis�et�al.�Drugs�Under�Experimental�&�Clinical�g g pResearch.��13(7):425�33,�1987.

5�Hydroxytryptophan� A�double�blind�cross�over�study�in�31�patients�with�chronic�primary�headache,�comparing�400�mg�per�day�of�p y , p g g p yL�5�HTP�to�placebo.�� Over�two�months�L�5�HTP�proved�to�be�more�effective�than�

l b i d i b th h d h f d itplacebo�in�reducing�both�headache�frequency�and�severity,�but�the�difference�was�not�statistically�significant.�

� Greater than 50% average reduction in headacheGreater�than�50%�average�reduction�in�headache�symptoms�were�obtained�in�48%�of�the�cases.�� De�Benedittis�et�al.�Journal�of�Neurosurgical�Sciences.��29:239�48,�1985.

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Tension�Headache• Double�blind�RCT�• 78�patients�with�chronic�T�T�HA�p• L�5�hydroxytryptophan (5�HTP)�300�mg�per�day�(n�=�43)�or�placebo�(n�=�35)�for�8�weeks,�after�a�washout�period�of�2 k2�weeks

• Follow�up�period�of�a�further�2�weeks.�• No significant decrease in HA days or HA intensity in the• No�significant�decrease�in�HA�days�or�HA�intensity�in�the�group�treated�with�5�HTTP�during�TX

• Significant�decrease�in�analgesics�taken• Significant�decrease�in�the�number�of�days�with�headache

during F/U

Ribeiro, CA.Ribeiro, CA. HeadacheHeadache 40(6):45140(6):451--6, 20006, 2000

Preventatives�with�some�evidence� Magnesium:�Chelated magnesium,�magnesium�oxide,�and�slow�release�magnesium�are�likely�to�be�the�best�absorbed.�The�daily�dose�is�400�mg.�Diarrhea�may�be�a�limiting�adverse�effect�in�some�patients.� Particularly�useful�in�pregnancy.

� Petasites hybridus (Petadolex):�75�mg�twice�daily�for�1�h h d lmonth,�then�50�mg�twice�daily.

� Feverfew:�100�mg�daily.

� CoQ10:�300�mg�daily.

� Riboflavin�(vitamin�B2):�400�mg�daily.

� Alpha�lipoic acid:�600�mg�daily.

Parker�et�al.• Aust�NZ�J�Med�(1978)�8:589�593�&�(1980)�10:192�198

• Patients�� Common�(61%)�or�classical�migraine�(39%)�with�mean�of�19�( ) g ( )years�duration.

• 85�patients�randomized�to�group�1�(chiropractic,�n=30),�group�2�( i l ti b di l d t 27) 3 ( bili ti b(manipulation�by�medical�doctor,�n=27)�or�group�3�(mobilization�by�physical�therapist,�n=28).

• Maximum of 2 months of twice weekly treatment.Maximum�of�2�months�of�twice�weekly�treatment.

• Results� At�2�months�post�treatment,�group�1�had�40%�fewer�HA's�and�43%�less�pain�with�HA's.��In�group�3,�similar�figures�were�34%�and�15%.��

( ) d dMean�pain�intensity�was�2.8�(VAS)�in�group�1�and�4.4�and�4.5�in�groups�2�and�3�(p<0.01).

Migraine�and�acupuncture� 114�migraneurs�� 12�weeks�of�acupuncture (8�15�Tx)�or�metoprolol�(100�200�mg�daily)�� Outcome:�#�of�migraine�days�in�weeks�9�to�12�

�Migraine�days�decreased�by�2.5�+/� 2.9�days�(baseline�5.8�/ 2 5 d ) ith t d t 2 2 / 2 7+/� 2.5�days)�with�acupuncture compared�to�2.2�+/� 2.7�days�(baseline�5.8�+/� 2.9�days)�in�metoprolol�group�(P=�.721).721)

� The�proportion�with�reduction�of�migraine�attacks�by�>�or�=50%)�was�61%�for�acupuncture and�49%�for�metoprololp

� Fewer�adverse�effects�in�the�acupuncture� High�drop�out�in�the�metoprolol�group

Streng, et al. Headache. 46(10):1492-502, 2006 21

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Migraine�and�acupuncture• RCT:�28�migraineurs;�real�or�sham�acupuncture• Semi�standardized�and�standardized�minimal�

acupuncture were�used– 16�Tx in�12�weeks.�

• Similar�reductions�in:�days�with�migraine,�frequency�of�migraine�attacks,�average�duration�of�a�migraine�attack,�rate of rescue medication used average headacherate�of�rescue�medication�used,�average�headacheseverity– Nausea�and�vomiting�not�different.�g

• Showed�that�semi�standardized�acupuncture shows�no�difference�from�sham�acupuncture

Alecrim-Andrade, et al.Cephalalgia. 26(5):520-9, 2006

Migraine�and�acupuncture� 302�migaineurs: Acupuncture,�sham�acupuncture,�or�waiting�list�control�

� 12�sessions�per�patient�over�8�weeks.�� Compare�4�weeks�before�to�12�weeks�and�21�to�24�weeks�after�randomization� HA�days�decreased�by�2.2�(baseline�5.2)�days�with�Tx;�decrease�by 2 2 (baseline 5 0) days in sham; and by 0 8 days (baselineby�2.2�(baseline�5.0)�days�in�sham;�and�by�0.8�days�(baseline�5.4)�in�waiting�list�group�

� No�difference�between�acupuncture and�sham� Proportion�of�responders�(>�50%�less�HA�days):51%�in�Tx;�53%�in�sham;�15%�in�waiting�list�

Linde, et al. JAMA. 293(17):2118-25, 2005

Acupuncture�in�Migraine• 140�migraine�patients�

• Acupuncture group treated: verum acupuncture (3/wk)Acupuncture�group�treated:�verum�acupuncture�(3/wk)�plus�daily�placebo

• Control group: sham acupuncture plus flunarizineControl�group:�sham�acupuncture�plus�flunarizine.

• Results:�acupuncture�group�had�better�responder�rates�(>50% improvement) and fewer migraine days compared(>50%�improvement)�and�fewer�migraine�days�compared�with�the�control�group�(P<.05)�at�4�and�16�wks.

• No significant differences in VAS scores and SF 36• No�significant�differences�in�VAS�scores�and�SF�36.

Wang LP et al. Efficacy of acupuncture for migraine prophylaxis: a single-blinded, double-dummy, randomized controlled trial . Pain, 06/01/2011

Acupuncture�in�T�T�Headachep• Acupuncture,�minimal�acupuncture (sham) or�no�

acupuncture ith T T HAacupuncture with�T�T�HA• 270�patients�with�episodic�or�chronic�T�T�HA12 i ti t i ht k• 12�sessions�per�patient�over�eight�weeks.– Outcome: four�weeks�before�with�weeks�9�12�

• HA days: decreased by 7 2 (SD 6 5) with TX; 6 6 (SD 6 0)• HA�days:�decreased�by�7.2�(SD�6.5)�with�TX;�6.6�(SD�6.0)�with�sham;�and�1.5�(SD�3.7)�with�“waiting�list”.�– Responders�(>�50%�reduction�in�HA�days):�46%�in�Tx;�35%�p ( y ) ;sham,�and�4%�waiting

• No�benefit�over�sham

Melchart, et al. BMJ. 331(7513):376Melchart, et al. BMJ. 331(7513):376--82, 200582, 2005 22

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Acupuncture in T�T HAAcupuncture�in�T T�HA�Acupuncture,�relaxation�training�and�physical�training chronic tension type headache (CTTH) Thetraining�chronic�tension�type�headache (CTTH).�The�study�comprised�

� 90 ti ti t ith CTTH� 90�consecutive�patients�with�CTTH��Measurements�4�weeks�before,�immediately�after,�and�3�and�6�months after the treatment periodmonths�after�the�treatment�period.�

� Immediately�after�the�last�treatment,�the�number�of�headache free periods and of headache free daysheadache�free�periods�and�of�headache�free�days�was�higher�in�the�relaxation�group�compared�with�the acupuncture groupthe�acupuncture group

Soderberg, et al. Cephalalgia. 26(11):1320Soderberg, et al. Cephalalgia. 26(11):1320--9, 20069, 2006

Acupuncture�in�chronic�daily�headachep y

• RCT:�74�patients�with�CDH�• Compared�medical�management�provided�by�neurologists�to�medical�management�plus�10�acupuncture treatments.�d l• Medical�management�group:�no�improvement�

• Medical�management�plus�acupuncture:3 0 i b (95% CI 1 0 4 9) h H d h I– 3.0�points�better�(95%�CI,�1.0�to�4.9)�on�the�Headache Impact�Test�

– Increase�>8�points�on�“role�limitations”�of�SF36p– 3.7�times�more�likely�to�report�less�suffering�at�6�weeks

Coeytaux, et al.Coeytaux, et al. HeadacheHeadache. 45(9):1113. 45(9):1113--23, 200523, 2005

MigraineMigraine• Migraine�is�different�in�older�individuals�and�in�children– Older people have less severe headaches thoughOlder�people�have�less�severe�headaches�though�can�have�many�of�the�other�things�that�go�with�migraine�� “migraine�equivalents”g g q

– Children�have�shorter�attacks�and�more�vomiting�(often cyclic vomiting)(often�cyclic�vomiting)

Migraine�Criteria�for�late�life�migraine�equivalents:�Fortification spectra/visual hallucination�Fortification�spectra/visual�hallucination

�Slow�evolution�of�visual�or�sensory�symptoms.

�Serial�progression�with�delays�between�symptoms

�Two�or�more�identical�attacks

�Duration�greater�than�20�minutes

�Midlife flurry of attacks.Midlife�flurry�of�attacks.

�Complete�recovery�with�normal�exam

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Childhood�Migraineg

�Childhood migraine:�Childhood�migraine:

�male�preponderance,�shorter�attacks,�prominent�vomiting,�abdominal�pain/�cyclic vomiting/ vertigo common, sleepcyclic�vomiting/�vertigo�common,�sleep�disturbance�common,�minor�head�trauma may trigger good prognosistrauma�may�trigger,�good�prognosis.

HA�in�children• By�age�3,�headache�occurs�in�3%�to�8%�of�children.�• At�age�5,�19.5%�have�headache,�and�by�age�7,�37�to�51.5%�have�headaches.�

• In�7�to�15�year�olds,�headache�prevalence�ranges�from�57%�t 82%to�82%.�

• The�prevalence�increases�from�ages�3�to�11�in�both�boys�and girls with higher headache prevalence in 3� to 5�year�and�girls�with�higher�headache�prevalence�in�3� to�5�year�old�boys�than�in�3� to�5�year�old�girls.�

• Thus, the overall prevalence of headache increases fromThus,�the�overall�prevalence�of�headache�increases�from�preschool�age�children�to�mid�adolescence�when�examined�using�various�cross�sectional�studies.

– Bigal�M.E., Liberman�J.N., Lipton�R.B., et�al: Age�dependent�prevalence�and�clinical�features�of�migraine.� Neurology 67. (2):�246�251,�2006

Riboflavin�for�HA�in�children� Retrospective�study�reports�on�our�experience�of�using�riboflavin�for�migraine�prophylaxis�in�41�pediatric�and�adolescent�patients,�who�received�200�or�400�mg/day�single�oral�dose�of�riboflavin�for�3,�4�or�6�months.�

� 77.1%�reported�that�abortive�drugs�were�effective�for�controlling�ictal events.�

� During�the�follow�up,�68.4%�of�cases�had�a�50%�or�greater�reduction�in�frequency�of�attacks�and�21.0%�in�intensity.�

� Riboflavin�well�tolerated.� Condò M,�Posar A,�Arbizzani A,�Parmeggiani A.�Riboflavin�prophylaxis�in�pediatric�

and adolescent migraine J Headache Pain 2009 Oct;10(5):361�5and�adolescent�migraine.�J�Headache�Pain.�2009�Oct;10(5):361 5.

Beware�the�diagnosis�of�Cluster�HA�– it�is�often�wrong!

� Diagnosis:� Diagnosis:

� Demographics:�Male�6:1,�Older�onset�(peak�20�50)

� Periodicity: "headaches with a clock" especially at night� Periodicity:� headaches�with�a�clock ,�especially�at�night

� Character:� paroxysmal/explosive/unilateral/periorbital pain, ipsilateral nasal� paroxysmal/explosive/unilateral/periorbital pain,�ipsilateral nasal�congestion/�lacrimation/�sweating/�Horner's�syndrome/�conjunctivalinjection.

h l h l� Location:�80�85%�have�ocular�pain,�80�85%�have�temporal�pain,�80�85%�have�frontal�pain,�50%�have�maxillary�pain,�50%�have�zygomatic pain 20�25% have nasal pain 20�25% have parietalzygomatic pain,�20 25%�have�nasal�pain,�20 25%�have�parietal�pain,�20�25%�have�occipital�pain

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Cluster Cluster� Treatment:

� P h d h O i ll f l� Per�headache:�Oxygen�� especially�for�nocturnal�attacks.�Ergotamine.�Lidocaine�� intranasal�infusion.�Capsaicin DHECapsaicin.�DHE

� Prophylaxis:�� treatment�for�projected�duration�of�cluster Ergotamine Prednisone Methysergidecluster.�Ergotamine,�Prednisone,�Methysergide,�Lithium,�Indocin,�calcium�channel�blockers

� ?Occipital nerve block Surgery� ?Occipital�nerve�block,�Surgery

�Manipulation?

Cervicogenic�Headacheg� Cervicogenic�headache�appears�to�be�a�relatively�common form of headache similar to migraine incommon�form�of�headache,�similar�to�migraine�in�prevalence.�� F t fi ti t ith h d h 5 d th� Forty�five�patients�with�headaches�5�or�more�days�a�month�were�interviewed�and�examined�with�respect�to�the�IHS�criteria�for�cervicogenic�headache.�g

�Of�the�45�persons�examined,�eight�fulfilled�the�diagnostic�criteria�for�cervicogenic�headache,�equivalent�to�a�prevalence�in�the�headache�group�of�17.8%�.� Nilsson.�Spine.��20:1884�8,�1995.

Cervicogenic�Headache• Neck�motion,�particularly�rotation�and�flexion/extension�is�limited�in�cervicogenic�headache– 51�control�subjects�and�90�HA�patients�(28�migraine,�34�T�T,�and�28�cervicogenic)

– Significant�differences�between�cervicogenic�headache�and�the�other�groups�for�rotation�&�flexion/extension,�but�not�lateral�

k tneck�movement�

– “Reduced�neck�mobility�is�one�of�the�major�criteria�for�this�diagnosis it emphasizes the need for systematic objective neckdiagnosis,�it�emphasizes�the�need�for�systematic,�objective�neck�mobility�measurements�in�the�individual�patient�to�substantiate�the�diagnosis.”

• Zwart�JA.�Headache.��37:6�11,�1997.

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Cervicogenic headacheCervicogenic�headache� Chiropractic�treatment�has�significant�benefit�on�patients with cervicogenic HApatients�with�cervicogenic�HA� 53�patients�with�cervicogenic�headache�randomized�to�chiropractic�Tx�twice�per�week�for�3�weeks�or�low�level�laser�treatment�of�the�upper�neck�and�deep�friction�massage�of�lower�neck�and�upper�back.

� Analgesic use dropped 36% headache hours per day dropped� Analgesic�use�dropped�36%,�headache�hours�per�day�dropped�69%�and�headache�intensity�dropped�36%�in�the�manipulated�group�(as�compared�with�no�decrease,�36%�decrease�and�17%�decrease in the control group respectively)decrease�in�the�control�group,�respectively).��� Nilsson�et�al.�JMPT.��20(5):326�30,�1997

ConclusionsConclusions• More�than�21�million�Americans�suffer�from�migraine�and�other�severe�headaches

• Most�had�seen�a�physician�but�many�(up�to�half)�undiagnosed

• 85%�had�cancelled�or�delayed�social�activities;�% y ;80%�of�employees�have�their�work�effected.

• Effective migraine treatment improves patientsEffective�migraine�treatment�improves�patients�lives.

ConclusionsConclusions• Many�patients�don’t�know�they�have�migraine�or�migranous�HA

• Only�1/3�of�very�satisfied�w/�treatment• Most�patients�had�tried�almost�5�options�before�effective�treatment�found

• Migraine�is�an�expensive�condition�in�terms�of�both�health care and societal costshealth�care�and�societal�costs

• A�natural�approach�can�make�a�significant�difference�in patients livesin�patients�lives

Managing�Headacheg g

Rand�Swenson,�D.C.,�M.D.,�Ph.D.Professor�of�Neurology�and�Anatomy

Dartmouth�Medical�School

Hanover,�NH

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