Headache in clinical practice

Surat Tanprawate, MD, MSc(Lond.), FRCPT The Northern Neuroscience Centre in collaboration with Division of Neurology, Faculty of Medicine Chiang Mai University

A man with chronic migraine addict to medication, diazepam, xanax, diazepam

A CM woman with addict to tramadol, cafergot, and pethidine iv

Tension-type headache and migraine are the 2nd and 3rd most prevalent medical disorders on the planet
!

Migraine accounts for 30% of the global burden and more than 50% of the disability burden attributable to all neurological disease worldwide
!

Overall, it is the 4th ranking cause among women and the 7th ranking cause of all disease-associated disability worldwide.

Lancet 2012; 380: 2197223

Patient presents with complaint of a headache Critical rst step:! Hx taking, physical exam Red ag signs or alarming signs Meets criteria for primary headache disorder?

Red ag signs
(+)

Investigation

(-)

(+)

Migraine! headache
Cluster headache and other TACs

Tension-type headache Chronic daily headache (CDH) Other (rare) headache disorder Secondary headache disorder

Abnormal neurological examination Normal neurological examination

Age Temporal prole
Worsening headache! -Mass lesion, SDH, MOH

Focal neurologic s/s other than typical visual or sensory aura Papilledema Neck stiffness

Concurrent event
Pregnancy, post partum! -Cerebral vein thrombosis, carotid dissection, pituitary apoplexy Headache with cancer, HIV, systemic illness (fever, arteritis, collagen vascular disease)

Provoking activity
Triggered by cough, exertion or Valsava! -SAH, mass lesion

Age> 50

Sudden onset! -SAH, ICH, mass lesion (posterior fossa)

Worse in the morning! -IICP Worse on awakening! -Low CSF pressure

The Headache Classication System Published

! Classication of Headache Disorder" ! International Classication in Headache Disorder (ICHD)" ! ICHD-I: 1988" ! ICHD-II: 2004

Last updated ICHD-III Beta version (Boston 2014)

Jes Olesen, MD, PhD University of Copenhagen, Glostrup Hospital, Denmark

ICHD-III Beta, 2013

Diagnostic criteria of common primary headache disorder

Migraine without aura

ICHD-III Cephalalgia.2013

Classic migraine (Migraine with aura)

The di!erent phases of a migraine attack

Aura in migraine

Jann AE Headache 2012 Apr;52(4):687-8.

Visual Aura
Zig-zag lines (fortication)

Zig-zag lines in migraine aura

Mosaic Illusion

Olomouc (c.1757) bastion fortress in today's Czech Republic

Body distortion in Migraine

Migraine art and Migraine in the literature

Podoll & Robinson, Migraine Art - The Migraine Experience from Within, 2008

Alice in the wonderland by Lewis Carroll

Lewis Carrolls migraine aura experience

Aura

Chiang Mai Headache Record Form

Cortical spreading depression(CSD) and Aura

They observed blood oxygenation level-dependent (BOLD) signal changes

Progression of the scintillations in the dark

CSD of cortical activation during migraine aura

CSD is a wave of neuronal and glial depolarization, followed by long-lasting suppression of neural activity
Hadjikhani PNAS 2001 98(8): 46874692

Pain characteristics and location of the acute migraine attack: A study of 1283 migraine patients
! Time of headache: morning in 18.7%, afternoon 13.5%, evening 4.0%, during night 9.4%, and "anytime" 54.3%" ! Headache character: throbbing (73.5%), aching (73.8%), pressure (75.4%), and stabbing (42.6%)" ! Headache increased by activity: 90.2% of patients" ! Headache location: eyes (67.1%), temporal (58.0%), and frontal (55.9%), di#usely (17.5%) and vertex (24.1%)" ! Hemi-cranial location: 66.6% of patients,
Kelman L. Headache 2005 Sep;45(8):1038-47. Kelman L. Headache 2006 Jun;46(6):942-53.

Mechanism of Head pain

Dorsolateral pontine activity features prominently in the pathophysiology of episodic migraine

Weiller C, et al Nat Med. 1995;1:658-660

Trigemino vascular activation

Other regions (pain matrix): right anterior cingulate, posterior cingulate, cerebellum, thalamus, insula, prefrontal cortex, and temporal lobes
Activation in the thalamus and insula in the migraine state.
Shazia K.Arch Neurol. 2005;62(8):1270-1275

New diagnostic criteria of Vestibular migraine (A1.1.6) : ICHD-III Beta version 2013
A. At least ve episodes fullling criteria C and D" B. A current or past history of 1.1 Migraine without aura or 1.2 Migraine with aura" C. Vestibular symptoms of moderate or severe intensity, lasting between 5 minutes and 72 hours D. At least 50% of episodes are associated with at least one of the following three migrainous features:"
1. headache with at least two of the following four characteristics: unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity" 2. Photophobia/phonophobia" 3. Visual aura"

E. Not better accounted for by another ICHD-III diagnosis or by another vestibular disorder ICHD-III Beta 2013

Cause
Genetic

Pathophysiology of acute migraine

Pathophysiology of episodic and chronic migraine

episodic

Environmental and factor

- Genetic" : FHM, TREK" ! -Trigger factor

Pathophysiology! - Aura" - vasodilatation" - neurogenic inammation" - peripheral and central sensitization" - Trigemino vascular system" Neurotransmitter! - Serotonergic system" - Dopaminergic system" Structural and functional brain change" - Brain stem activation

constant

episodic become chronic

acute on chronic

Clinical: chronic and transform migraine, allodynia, neck pain" ! Anatomical: PAG, central sensitization

Evolution of Migraine

Migraine is considered as a chronic disorder with episodic attacks (CDEA)

Conceptualized of clinical course of migraine
LFEM 0-9 days of headache/month

No migraine

HFEM 10-14 days of headache/month

Chronic Migraine

Factor for Migraine progression

- Gene - Age/Sex - Triggers - Attack frequency - Obesity - Medication overuse - Stressful life event - Caffeine overuse - Snoring - Other pain syndrome

Bigal and Lipton Neurology 2008;71;848-855

From papyrus, 2500 BC

At the Northern Neuroscience Center, 2012

From papyrus, 2500 BC

Migraine management

Comprehensive treatment plan

Education, reassurance and life

style modication!

Avoiding triggers to prevent attack! Non-phamacologic treatment! Treating the acute attack! Long-term preventive therapy! Physical and alternative medicine
Silberstein SD. Wolffs headache. 2008

Successful treatment

Episodic Migraine Frequent migraine attack

Life style

modication! Acute migraine treatment

+ Prophylaxis medication

Treatment fail
Inadequate treatment
- Life style modication?! - Right drug, dose, duration?

Migraine with co-morbidity

- Psychiatric condition! - Sleep condition

Migraine with MOH

True refractory migraine

use acute medication > 15days/months, ! > 3 months

failed > 3 preventive medication group

Pharmacotherapy of acute migraine attack

Non-specic!

Acetaminophen, ! NSAIDs! ca"eine! opioids! neuroleptic

Dihydroergotamine! Ergotamine! Triptan

Specic!

Non-specic migraine medication:! !

Analgesics with evidence of efcacy! EFNS migraine treatment guideline 2009
Evers, S et al. European Journal of Neurology 2009, 16: 968981

Ergotamine

Ergot
Cock spur The ergot of Rye

The word ergot is derived from argot, old French for cock spur

Fungus Claviceps

purpurea
400 BC: ergotism was reported ! - vasospasm! - gangrene! - abortion 1862: ergot use to treat migraine

Contraindication of ergot use...

coronary, cerebral and peripheral vascular disease! pregnancy! renal or hepatic failure! uncontrolled hypertension! sepsis! hypersensitivity reaction! hemiplegic and basilar type migraine! migraine with prolong aura

Triptans
(Imigran)

Time to peak plasma(h)

(Zomig)

Sumatriptan Zolmitriptan Eletriptan

2.5 3.3 1.0-2.0

(Relpax)

Evers, S et al. European Journal of Neurology 2009, 16: 968981

Preventive Medication
Aim!

Reduce attack frequency, severity, and duration! Improve responsiveness to acute headache therapies! Improve function and reduce disability! Reduce overall cost associated with migraine treatment

Indication for preventive treatment in migraine

Recurring migraine that signicantly interferes with quality of
life

Frequency of migraine attacks > 1/weeks Frequency of acute medication use>2/week Failure of, contraindication to, or trouble AE from acute
medication

Uncommon migraine: hemiplegic migraine, basilar migraine,

Pract Neurol 2007; 7: 383393

prolonged, disabling or frequent aura, or migrainous cerebral infarction

Concept
Right drug Right person Right dose
Right duration
Preventive medication that was proven the efcacy Consider patient proles, and co-morbidities Titrate into the appropriated dose On the preventive therapy long enough

Loder Elizabeth. Headache 2012;52:930-945

Loder Elizabeth. Headache 2012;52:930-945

Indications, contraindications, and adverse effects of conventional migraine preventive drugs

Drugs
Amytriptiline (TCA)! ! ! ! ! Propranolol (Bblocker)! ! ! ! Flunarizine (CCB)! ! ! Valproic acid (AED)! ! ! ! Topiramate (AED)

Relative indications

Relative contraindication

Adverse effect

Other pain disorders, Mania, urinary Drowsiness, dry depression, anxiety, retention, heart mouth, increase insomnia! blocks, glaucoma! appetite, weight gain! ! ! ! ! ! ! Hypertension, angina! Asthma, depression, Fatique, lethargy, ! CHF, Raynauds nausea, depression, ! disease! dizziness! ! ! ! ! ! ! Hypertension, vertigo! Obesity, depression, Drowsiness, weight ! PD! gain, depression, PD! ! ! ! Epilepsy, mania, Liver disease, Nausea dyspepsia, anxiety! bleeding disorder! sedation, increase ! ! appetite, weight gain! ! ! ! Epilepsy, mania, Renal calculosis, liver Paresthesia, weight anxiety disease loss, alter taste, language disturbance
F. Galletti et al. Progress in Neurobiology 89 (2009) 176192

Obesity and migraine

Overweight increase!

number of Chronic daily headache! prevalence of transform migraine!

Proposed mechanism!
obesity = pro-inammatory state! adepocyte secrete IL-6, TNF! increase plasma CGRP; elevate brain CGRP??
Bigal ME, et al. Neurology. 2006;66:545-550 Bigal ME, and Lipton RB. Neurology. 2006;67:252-257

Obesity and migraine: A population study

Proportion of migraineurs with 10 or more headache days per month according to the body mass index
BigalME, et al. Neurology. 2006;66:545-550.

Change in Body Weight: Double-Blind Phase (26 weeks)

Poster presented at the American Headache Society 46th meeting. Vancouver, 2004

Weight management

Maintain the weight or decrease it! Drug used for reducing weight! Drug for migraine prevention affecting to weight!

neutral weight: beta-blocker, Ca-blocker! increase weight: Valproic acid, TCA! reduce weight: Topiramate

Inuence of anxiety and depression (HAD scores) on migraine-related disability (MIDAS grade)! in FRAMIG study

Psychiatric comorbidity management

Early identify psychiatric comorbidity!

using depression, anxiety screening tool: Hospital Anxiety Depression Scale (HADS)!

Use/avoid preventive migraine drug that have an effect to psychiatric comorbidity!

Favor: TCA(depression), Depakine (mood), Topiramate(anxiety), propranolol(panic)! Avoid: Propranolol(depression)!

Consult psychiatrist

Topiramate adverse events

Placebo! (n=445)
Taste perversion Weight decrease Taste perversion Weight decrease Taste perversion Weight decrease Taste perversion

Topiramate
50 mg/d! (n=235) 100 mg/d! (n=386) 200 mg/d! (n=514)

6 11 6 8 4 1 1

35 14 9 9 9 6 15

51 15 15 13 11 9 8

49 19 14 14 11 11 12

Poster presented at the American Headache Society 46th meeting. Vancouver, 2004

Recommended Migraine Prophylaxis Dosing and Titration

AM Dose Week 1 Week 2 Week 3 Week 4 None 25 mg 25 mg 25 mg PM Dose 25 mg 25 mg 50 mg 50 mg

Brandas JL. Headache 2005;45 [Suppl1]:S66-S73

Continue preventive medication for 4-6 months

Public
What we gain from pain, what we fail from pills: TEDx Talk Chiang Mai

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