1. 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 Head
Institute of Neurology, Madras Medical College
Adjunct Prof.
IIT Madras

2. IHS Guidelines
Diagnosis of Migraine
Presence of two or more Presence of one or more
Head related symptoms Non headache symptoms
1. Moderate to severe Pain 1. Aura
2. Pain on one side of head 2. Nausea during headache
3. Throbbing Pulsating 3. Photophobia, Phonophob
headache ia during headache
4. Headache exacerbated
by routine activities

3. How to approach the patient
with a headache ?

4. Patients presents with complaint
of a headache
Diagnosis
Algorithm
Critical first steps :
• Detailed history
• Focused physical examination
• Focused neurological examination
• BP, Ocular/Fundus Examination
Worrisome Headache: Red Flags – “SNOOP””
no
Meets criteria for Consider secondary headache disorder Specialty
primary headache no consultation
indicated
disorder?
Migraine
Cluster Headache
yes Tension-type Headache
Other headaches - sinus

5. 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

6. 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

7. 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)

8. 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

9. IHS Classification System: Primary Headache
 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

10. 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.)

11. 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

12. Tension Headache vs Migraine

13. 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.

14. Comparison of Most Common Primary Headaches
CHARACTERISTIC MIGRAINE TENSION CLUSTER
Age of onset 25 to 55 years 30 to 50 years 20 to 40 years
Unilateral (but may be Unilateral, orbital,
Location Bilateral
bilateral) 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 Boring, searing
pulsating
Pattern 1 to 2 attacks per month <180 attacks per year (or 1 to 8 attacks per day
<15 attacks per month) separated by pain- free
periods
Associated Nausea, vomiting, Either photophobia or Conjunctival injection
symptoms photophobia, phonophobia, but not both, Lacrimation
phonophobia (2 of no nausea or vomiting Forehead/facial swelling
these) Nasal congestion
Rhinorrhea Ptosis Miosis
Eyelid edema

15. MIGRAINE MAY OFTEN BE MISDIAGNOSED
As
SINUS HEADACHE
– SIMILAR DISTRIBUTION OF PAIN
– MIGRAINES CAN BE SEASONAL
– WITHDRAWAL FROM DECONGESTANTS CAN
PRECIPITATE MIGRAINES

16. Sinus-related headache may also confuse
the diagnosis of migraine
Parameters Sinus headacheMigraine
Face Pain + -
Infection + -
Upper Respiratory Problems + -
Fever, purulent discharge and
postnasal drip + -
Pale or pink nasal mucosa + +/-
Significant sinus fluid levels + -

17. 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

18. Performing the neurological
examination
• mental status • sensation
• level of consciousness • pathologic reflexes (e.g.
• cranial nerve testing Babinski's sign)
• pupillary responses • cerebellar function and gait
• funduscopic exam testing
• motor strength testing • signs of meningeal
irritation (Kernig's and
• deep tendon reflexes
Brudzinski's signs).

19. Fundoscopic exam
• Papilledema

20. IHS Classification System: Secondary Disorders
 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

21. Treat the migraine attack,
Prevent the disorder

22. Principles of Prevention
Factors Influencing Medication Choice
AE Profile Migraine Type
Coexisting Relative Drug
Conditions Efficacy
Patient
Preference

23. 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)

24. 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

25. 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

26. Candidates for migraine prevention
US-Guidelines for the use of preventive medication
• Recommendations are based on
1. 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

27. Candidates for migraine prevention
US-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

28. 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

29. Guidelines for migraine prophylaxis
Duration of therapy
• Preventive therapy to be continued for atleast 1 year
Peterlin BL. Headache 2008;48: 805-819
• 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
Freitag FG. Clinical Therapeutics 2007; 29: 939-949
• A full therapeutic trial can take 2 – 6 months
Silberstein SD. Trends in Pharmacological Sciences 2006; 27: 410-415

30. Potential Mechanisms of preventive medication
Silberstein SD. Trends in Pharmacological Sciences 2006; 27: 410-415

31. Prophylactic Treatment Of Migraine
Assess factors that may trigger migraine
First-line treatment:
- Calcium channel blockers (flunarizine) Reinforce education and lifestyle management
- Beta-blockers Consider other therapies (biofeedback, relaxation)
- Anti-epileptic drugs – (Divalproex & Topiramate) Screen for depression and generalized anxiety
yes
Successful ?* Continue treatment for 6-
no 12 months, then reassess
Try combination
Successful ?*
yes Continue treatment for 6-
12 months, then reassess
no
* A migraine prophylaxis is considered successful if the
Refer to Neurologist or Headache Specialist frequency of migraine attacks per month is decreased
atleast by 50% within 3 months.

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

33. Migraine activity starts in the Cortex

34. Cortical spreading depression (CSD) a
main culprit behind migraine attacks
Patients with migraine exhibit
high cortical excitability
Cortical hyperexcitability
Frequency of migraine Attacks
National Headache Foundation Migraine Prevention Summit Proceedings 2006

35. 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

36. To prevent CSD
Its necessary to block both the channels:
Na+ and Ca++

37. Na + and Ca2+ current inhibition by
Flunarizine
Concentration-dependent effects of FLN on I Na Concentration-dependent effects of FLN on I Ca
Q.Ye,etal., Chinese Medical Journal 2011;124(17):2649-2655

38. Flunarizine

39. 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

40. 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

41. 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%

42. Flunarizine vs Propranolol
Post Treatment Benefits
90
80
% of respondents
70
60
50
40
30
N = 45
0
Flunarizine Propranolol
% of patients with very good or excellent response
in terms of global evaluation after 45 days of drug withdrawal
Bordini CA et al. Arquivos de Neuro-Psiquiatria 1997; 55 :536-541.

43. Antiepileptic drugs side effects
Drug Dose Common Contraindications
Valproic acid 500-1800 Tiredness, cognitive deficits, dizziness, hepatic disease or
mg upset stomach significant hepatic
nausea, vomiting, hair loss, weight dysfunction,
gain, depression, tremor, pancreatitis, childbearing
hepatitis (test of liver function potential, pregnancy
necessary during treatment)
Topiramate 25-100 mg Paresthesia, Dizziness, Asthenia, Weight childbearing
Decrease, Somnolence, Difficulty with potential, pregnancy
Memory, Depression, Difficulty with
Concentration/Attention, Anxiety, Taste
Perversion, Upper Respiratory Tract
Infection, Suicidal thinking, diabetes,
kidney stones
EFNS guidelines on the drug treatment of migraine. European Journal of Neurology 2009, 16, 968-981

44. Migraine progression
- Consequence of CSD
- Headache 2008;48:7-15)
44

45. 3 Types of Migraine Progression
Clinical Increase in attack frequency
Migraine Physiological/
Progression Alterations in pain pathways
functional
Anatomical Neurological damage
45

46. 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.
Reference: Headache 2008;48:1044-1055
46

47. Study details
Journal 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

48. Prevent the
progression from
Episodic to
Chronic Migraine
Start
Early Effective Migraine
Prophylaxis

49. Thank you