Practice Pearls : Diagnosis & Prophylaxis of Migraine

Prof. A.V. SRINIVASAN,MD, DM, Ph.D,DSc(HON) F.A.A.N, F.I.A.N.

Emeritus Professor The Tamilnadu Dr. M.G.R. Medical University

Former HeadInstitute of Neurology, Madras Medical College

Adjunct Prof. IIT Madras

Prof. A.V. SRINIVASAN,MD, DM, Ph.D,DSc(HON) F.A.A.N, F.I.A.N.

Emeritus Professor The Tamilnadu Dr. M.G.R. Medical University

Former HeadInstitute of Neurology, Madras Medical College

Adjunct Prof. IIT Madras

IHS Guidelines Diagnosis of Migraine

Presence of two or more Head related symptoms

1. Moderate to severe Pain

2. Pain on one side of head

3. Throbbing Pulsating headache

4. Headache exacerbated by routine activities

Presence of one or more Non headache symptoms

1. Aura2. Nausea during

headache3. Photophobia,

Phonophobia during headache

How to approach the patientwith a headache ?

Diagnosis

Algorithm

Patients presents with complaint of a headache

Critical first steps :• Detailed history• Focused physical examination• Focused neurological examination• BP, Ocular/Fundus Examination

no

Meets criteria for primary headache

disorder?

yes

Consider secondary headache disorder Specialty consultation

indicated

Migraine

Cluster Headache

Tension-type Headache

Other headaches - sinus

Worrisome Headache: Red Flags – “SNOOP””

no

SNOOP• Systemic Symptoms such as fever or weight loss or Secondary Risk

factors as HIV or systemic cancer

• Neurologic Symptoms or abnormal signs such as confusion, impaired alertness, papilloedema, asymmetry, motor weakness, nuchal rigidity, visual disturbance other than aura, dysphasia

• Onset Sudden, abrupt, split-seconds to minutes, rapid onset of headache

• Older New headache onset in an older patient or a progressively worsening headache in a middle-aged patient (>50 years of age)

• Progression Previous headache history-A major change in attack frequency, severity, or clinical features; a first headache pattern or different headache unlike any experienced before

Simplifying history taking for migraine diagnosis

Sensitivity to light &/or sound

Unilateral or bilateral

Stomach uneasiness

Pulsating or throbbing headache

Episodic headache

Connected with

Triggers

Migraine: Triggers

Migraines occur in response to stimuli in up to 85% of patients

Common triggers related to :• Environment (weather changes, smoke,

bright lights, certain smells) • Emotions (stress, anxiety, crying) • Change in sleep pattern • Diet (cheese, red wine, chocolate, nitrates) • Skipping meals • Estrogen (menstrual cycle)

Detailed History• Characteristics of the headache• Assess functional impairment• Past medical history• Family history of migraines• Current medications and previous medications for headache

(Rx and over-the-counter)• Social history• Review of systems – to rule out systemic illness

Diagnosis of migraine currently based on International Headache Society (IHS) classification

Primary headache is headache not caused by

another disorder

Migraine and tension-type account for 75%-90% of primary headache

IHS Classification System: Primary Headache

Migraine Episodic, throbbing, usually unilateral headache May be preceded by visual, sensory or speech

disturbances and also accompanied by nausea, vomiting

Tends to be disruptive, a significant loss in quality of life and inability to perform their daily activities

Migraine is a heterogeneous disorder

- attacks vary in their frequency, duration, severity and number of associated symptoms

Duration : 4 – 72 hrs (average 24 hrs.)

Tension headaches

• Band-like, bilateral• Tightness/pressure/dull

ache• Radiates to neck and

shoulders• Mild to moderate• Not aggravated by

movement• 30 min to several days

Tension Headache vs Migraine

Cluster headache

• Rare condition that can be acute or chronic in nature

• Characterized by 1-3 short-lived i.e. 15min – 3hrs (avg. 45 min) attacks of peri-orbital pain

• Occurs in clusters for 2-3 months, followed by pain-free interval of one year

• Attack often associated with red tearing eyes, nasal stuffiness and ptosis.

CHARACTERISTIC MIGRAINE TENSION CLUSTER

Age of onset 25 to 55 years 30 to 50 years 20 to 40 years

Location Unilateral (but may be bilateral) Bilateral Unilateral, orbital,

supraorbital, temporal

Duration of episode 4 to 72 hrs 30 min to 7 days 15 to 180 min

Severity Moderate to severe Mild to moderate Extremely severe

Type Pulsating, throbbing Pressing, tightening but not pulsating

Boring, searing

Pattern 1 to 2 attacks per month <180 attacks per year (or <15 attacks per month)

1 to 8 attacks per day separated by pain- free periods

Associated symptoms

Nausea, vomiting, photophobia, phonophobia (2 of these)

Either photophobia or phonophobia, but not both, no nausea or vomiting

Conjunctival injection Lacrimation Forehead/facial swelling Nasal congestion Rhinorrhea Ptosis Miosis Eyelid edema

Comparison of Most Common Primary Headaches

MIGRAINE MAY OFTEN BE MISDIAGNOSED As

SINUS HEADACHE

– SIMILAR DISTRIBUTION OF PAIN

– MIGRAINES CAN BE SEASONAL

– WITHDRAWAL FROM DECONGESTANTS CAN PRECIPITATE MIGRAINES

Sinus-related headache may also confuse the diagnosis of migraine

Parameters Sinus headacheMigraineFace Pain + -Infection + -Upper Respiratory Problems + -Fever, purulent discharge and postnasal drip + -Pale or pink nasal mucosa + +/-Significant sinus fluid levels + -

Performing the physical exam

• PE should include vital signs, a complete neurologic exam (including funduscopic exam), CV, head, and neck exam

• A complete neurologic examination is essential

Performing the neurological examination

• mental status• level of consciousness• cranial nerve testing• pupillary responses• funduscopic exam• motor strength testing• deep tendon reflexes

• sensation• pathologic reflexes (e.g. Babinski's sign)• cerebellar function and gait testing

• signs of meningeal irritation (Kernig's and Brudzinski's signs).

Fundoscopic exam

• Papilledema

Secondary headache disorders are a symptom of another disease

A common type of secondary headache is called

rebound headache - the result of overuse of analgesic medications (MOH)

Another type is sinus headache - sometimes incorrectly diagnosed when condition is really migraine

IHS Classification System: Secondary Disorders

Treat the migraine attack, Prevent the disorder

AE Profile Migraine Type

Relative Drug Efficacy

Coexisting Conditions

Patient Preference

Principles of Prevention Factors Influencing Medication Choice

Acute Therapy: Pros and Cons

POSITIVES: – Rapid onset of action – Ideal for occasional migraine

NEGATIVES: – Doesn’t address frequency of attacks or impact on quality of life – If not taken at onset, less effective – Acute therapies not always effective – Undesirable side effects – Frequent use can cause medication overuse headache

(“rebound” headache)

MIGRAINE PROPHYLAXIS

Aim of pharmacologic prophylaxis in migraine:

1. reducing the number of migraine days per month,

2. reducing headache pain and associated symptoms,

3. shortening individual attacks,

4. improving the effect of acute medication,

5. preventing medication-overuse headache

Preventive Therapy: Advantages

• Reduces frequency of migraines, so that the patients can live more normal & productive life

• Reduces use of acute medications – and possible “rebound” headache

• Reduces overutilization of medical resources, including: • Emergency room visits • Physician office visits

Candidates for migraine preventionUS-Guidelines for the use of preventive medication

• Recommendations are based on1. headache days per month

experienced by migraine patients

2. Level of attack-related impairment caused by the headaches

Migraine prevalence, disease burden, and the need for preventive therapy,Lipton et al. Neurology 2007;68;343-349

Candidates for migraine preventionUS-Guidelines for the use of preventive medication

• II. Prevention should be considered: – Patients with 4 or 5 migraine days per

month with normal functioning, – 3 migraine days with some

impairment, or – 2 migraine days with severe

impairment.

Migraine prevalence, disease burden, and the need for preventive therapy,Lipton et al. Neurology 2007;68;343-349

Guidelines for migraine prophylaxis Successful therapy

A migraine prophylaxis is considered successful if the frequency of migraine attacks per month is decreased atleast by 50% within 3 months

Evers S et al. Eur J Neurol 2006;13:560-572

• Preventive therapy to be continued for atleast 1 year

• Preventive therapy needs to be taken everyday because it requires dose-titration and may take several months to achieve the desired effect.

• Therapy from 6 to 12 months may be required, before evaluation of efficacy

• A full therapeutic trial can take 2 – 6 months

Freitag FG. Clinical Therapeutics 2007; 29: 939-949

Silberstein SD. Trends in Pharmacological Sciences 2006; 27: 410-415

Peterlin BL. Headache 2008;48: 805-819

Guidelines for migraine prophylaxis Duration of therapy

Potential Mechanisms of preventive medication

Silberstein SD. Trends in Pharmacological Sciences 2006; 27: 410-415

Prophylactic Treatment Of Migraine

Assess factors that may trigger migraineFirst-line treatment:

- Calcium channel blockers (flunarizine)- Beta-blockers - Anti-epileptic drugs – (Divalproex & Topiramate)

Successful ?*

Try combination

no

yesContinue treatment for 6-12 months, then reassess

Successful ?*

Refer to Neurologist or Headache Specialist

no

yes Continue treatment for 6-12 months, then reassess

* A migraine prophylaxis is considered successful if the frequency of migraine attacks per month is decreased atleast by 50% within 3 months.

Reinforce education and lifestyle management Consider other therapies (biofeedback, relaxation)Screen for depression and generalized anxiety

Techniques in Regional Anesthesia and Pain Management 2009;13:20-27.

Migraine activity starts in the Cortex

Patients with migraine exhibit high cortical excitability

Cortical hyperexcitability

Frequency of migraine Attacks

National Headache Foundation Migraine Prevention Summit Proceedings 2006

Cortical spreading depression (CSD) a main culprit behind migraine attacks

Migraine - A Channelopathy

Genetic mutations leads to defective Na+ and Ca+

+ channels which are linked to migraine

Widely used drugs for migraine prevention work by inhibiting the function of one or both of these ion channels(Na+, Ca2+)*

*Cohen et al ,Medical Hypotheses (2005) 65, 114–122

To prevent CSD

Its necessary to block both the channels:Na+ and Ca++

Na + and Ca2+ current inhibition by Flunarizine

Concentration-dependent effects of FLN on I CaConcentration-dependent effects of FLN on I Na

Q.Ye,etal., Chinese Medical Journal 2011;124(17):2649-2655

Flunarizine

Beta-blockers compared with Placebo

• Early studies can be criticized from a methodological point of view

• Propranolol, nadolol, timolol, metoprolol and atenolol have shown better efficacy than placebo in RCT

• Some trials failed to show a significant prophylactic effect of propranolol

• Two RCT have not shown any effect in the acute treatment of attacks

Beta-blockers compared with Placebo

• Early studies can be criticized from a methodological point of view

• Propranolol, nadolol, timolol, metoprolol and atenolol have shown better efficacy than placebo in RCT

• Some trials failed to show a significant prophylactic effect of propranolol

• Two RCT have not shown any effect in the acute treatment of attacks

Beta-blockers: side effects

• Propranolol 80-0-80 mg– With side effects 35 %– Without side effects 48 %

• Most commonly reported– Fatigue 18 % – Dizziness 2 %– Nausea 6 %– Sleep disturbances 4 %– Depression 4 %– Abnormal dreaming 2 %

Flunarizine vs Propranolol

Post Treatment Benefits

Bordini CA et al. Arquivos de Neuro-Psiquiatria 1997; 55 :536-541.

30

60

50

80

70

0

90

40

N = 45

% o

f res

pond

ents

PropranololFlunarizine% of patients with very good or excellent response

in terms of global evaluation after 45 days of drug withdrawal

Antiepileptic drugsDrug Dose Common side effects Contraindications

Valproic acid 500-1800 mg

Tiredness, cognitive deficits, dizziness, upset stomachnausea, vomiting, hair loss, weight gain, depression, tremor, pancreatitis, hepatitis (test of liver function necessary during treatment)

hepatic disease or significant hepatic dysfunction,childbearing potential, pregnancy

Topiramate 25-100 mg Paresthesia, Dizziness, Asthenia, Weight Decrease, Somnolence, Difficulty with Memory, Depression, Difficulty with Concentration/Attention, Anxiety, Taste Perversion, Upper Respiratory Tract Infection, Suicidal thinking, diabetes, kidney stones

childbearing potential, pregnancy

EFNS guidelines on the drug treatment of migraine. European Journal of Neurology 2009, 16, 968-981

Migraine progression

- Consequence of CSD

44

- Headache 2008;48:7-15)

45

Migraine Progression

Clinical

Anatomical

Physiological/ functional

3 Types of Migraine Progression

Increase in attack frequency

Alterations in pain pathways

Neurological damage

Anatomical progression - Neurological damage in Migraine

• Neuroimaging findings of a large-scale population-based study showed that silent brain damage is more frequent in migraineurs, compared with control subjects.

• Migraine is associated with white matter lesions.

• Clinical studies reported that migraine is a risk factor for ischemic stroke in younger women.

46

Reference: Headache 2008;48:1044-1055

Study detailsJournal of Headache Pain (2011) 12:47–53 Official journal of European Headache Federation• Study results• Flunarizine reduced

– Number of CSD waves– Amplitude of CSD waves – Duration of CSD waves

Flunarizine a potent CSD inhibitor

FLN does not only prevent the migraine disorder but also may reduce complications of migraine like neurological damage

Prevent the progression from

Episodic to Chronic Migraine

StartEarly Effective Migraine

Prophylaxis

Thank you