8. Pathophysiology
Vascular theory
It was believed that ischemia induced by intracranial
vasoconstriction is responsible for the aura of migraine and the
subsequent rebound vasodilation and activation of perivascular
nociceptive nerve resulted in headache.
Based on 3 observations -:
1. Extracranial vessels become distended and pulsatile during an
attack
2. Stimulation of an intracranial vessels in an awake person induces
headache
3. Vasoconstrictors improve the headache and vaso dilators provoke
an attack 8
9. Patho Physiology contd…
Neurovascular theory
∗ Complex series of neural and vascular events initiates migraine
∗ Migraine is primarily a neurogenic process with secondary
changes in cerebral perfusion
Cortical spreading depression
∗ CSD is a well defined wave of neuronal excitation in the cortical
grey matter that spreads from its site of origin at the rate of 2-
6mm/min
∗ This cellular depolarization causes the primary cortical
phenomenon aura phase, in turn, it activates trigeminal fibers
causing headache. 9
10. Patho Physiology contd…
Vasoactive substances and Neurotransmitters
∗ Perivascular nerve activity results in release of substances
such as substance P, neurokinin A, CGRP and NO which
produce vessel dilation, protein extravasation and sterile
inflammation stimulating the trigeminocervical complex.
Cutaneous Allodynia
∗ Secondary pain pathways of the trigeminophthalamic system
become sensitized during a migraine attack.
10
11. Patho Physiology contd…
Dopamine pathway
∗ Some of the symptoms associated with migraine such as nausea,
vomiting, yawning, hyperactivitycan be attributed to
dopaminergic stimulation.
Endothelial dysfunction
Serotonin and migraine
∗ Plasma extravasation mediated by vasoactive substances is
blocked by ergots, sumatriptan, indomethacin, GABA agonists
and benzodiazepines
∗ 5HT-1D receptors in trigeminal sensory neurons and 5HT 1B
receptors are present on smooth vessels in the meningeal
vessels 11
12. Etiology
∗ Approx 70% of patients have a first degree relative with a history
of migraine.
Familial Hemiplegic Migraine
∗ Migraine with aura that is preceded or followed by hemiplegia
that typically resolves
∗ FHM type 1 - Linked to mutations in the calcium channel gene –
chromosome 19.May be associated with cerebellar ataxia
∗ FHM type 2 - mutation in the sodium channel gene ATP1A2 on
chromosome 3
∗ FHM type 3- mutation in a sodium channel alpha subunit coding
gene
12
13. Etiology contd…
Migraine in inherited disorders -:
1. MELAS (mitochondrial myopathy, encephalopathy and lactic
acidosis)
2. CADASIL (cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy)
3. Genetic vasculopathies like RVCL (retinal vasculopathy with
cerebral leukodystrophy) etc.
13
14. Epidemiology
∗ Migraine accounts for 64% of severe headaches in females and
43% of severe headaches in males.
Migrain Without Aura Migraine with Aura
Boys Girls Boys Girls
Peaks at 5 years 12-13 years 10-11 years 14-17 years
∗ In individuals >12yr of incidence increases with age, reaching a
peak at 30-40 yrs
∗ F:M = 3.5:1 at 40yrs
14
15. Clinical presentation
History
∗ U/L, throbbing or pulsatile localized in the frontotemporal and
ocular areas but be felt anywhere around the head or neck.
∗ Pain builds over 1-2 hrs and become diffuse.
∗ Many patient prefer to lie in dark room
Other symptoms
∗ Nausea, vomiting, anorexia and food intolerance occur in about
50 % of patients. Photophobia and phonophobia are commonly
associated with headache.
∗ Hemiparesis, confusion, apathy 15 numbness.
and
16. Clinical presentation contd…
Prodrome
∗ About 60% of patients report premonitory symptoms that occur
hours to days before headache onset.
∗ Heightened sensitivity to light, sounds and odors.
∗ Lethargy or uncontrollable yawning.
∗ Food cravings
∗ Mental and mood changes
∗ Excessive thirst and polyuria
∗ Anorexia
∗ Constipation or diarrhea
16
17. Aura
∗ It is a complex of neurologic symptoms that may precede or
accompany the headache phase or may occur in isolation.
∗ Usually develops over 5-20min and lasts less than 60 minutes.
∗ Can be visual, sensory, motor or combination of these
Negative symptoms -:
∗ Negative scotoma
∗ Negative visual phenomenon such as homonymous hemianopia,
central scotoma, tunnel vision, altitudinal visual defects etc.
17
18. Aura contd…
Positive symptoms
∗ Scintillating scotoma-highly characteristic of migraine
∗ Photopsia or flashes of light
∗ Heat waves
∗ Micropsia, macropsia
Paresthesia
Occurring in 40%of cases constitute the next most common aura.
∗ Sensory symptoms rarely occurs in isolation and usually follows visual
aura.
∗ Motor symptoms may occur in 18% of patients
∗ Speech and language disturbances have been reported in 17-20% of
patients 18
25. ∗ Family history
∗ Approx 70% of patients have a first-degree relative with a
history of migraine
∗ Disability assessment
∗ Simple questionnaires like MIDAS migraine disability
assessment can be used to quantify the disability and for
follow up
25
26. Physical Examination
∗ Thorough neurologic examination is essential, results will be
normal in majority
∗ Possible findings may include
∗ Cranial/cervical muscle tenderness
∗ Horner syndrome
∗ Tachycardia/ bradycardia
∗ Conjunctival injection
∗ Hypertension/hypotension
∗ Hemisensory/ hemiparetic neurological deficits
( complicated migraine) 26
27. Physical Examination contd…
∗ Findings that suggest a headache diagnosis other than
migraine
∗ Dim scotoma lasting a few seconds to several minutes ie
amaurosis
∗ Temporal artery tenderness
∗ Meningisnus
∗ Mental status changes
∗ Focal neurologic deficit eg confusion, seizures
27
28. Physical Examination contd…
∗ Focal neurologic findings that occur with headache and
persist temporarily after the pain resolves suggests a
migraine variant
∗ U/L paralysis or weakness-hemiplegic migraine
∗ Aphasia, dysarthria, vertigo, tinnitus, syncope, balance
problems-basilar migraine
∗ Third nerve palsy with sparing of pupillary response-
ophthalmoplegic migraine
28
29. Diagnostic criteria
∗ Migraine without aura
Diagnostic criteria:
A. At least 5 attacks fulfilling criteria B-D
B. Headache attacks lasting 4-72 hours (untreated or
unsuccessfully treated)
C. Headache has at least two of the following characteristics:
1. unilateral location
2. pulsating quality
3. moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical
activity (eg. walking or climbing stairs)
29
30. Diagnostic criteria contd…
∗ D. During headache at least one of the following:
1. nausea and/or vomiting
2. photophobia and phonophobia
∗ E. Not attributed to another disorder
30
31. Migraine with aura
Diagnostic criteria -:
A. At least 2 attacks fulfilling criterion B
B. Migraine aura fulfilling criteria B and C for one of the
subforms 1.2.1-1.2.6 as per the IHS classification
C. Not attributed to another disorder
31
32. Typical aura
with migraine headache
A. At least 2 attacks fulfilling criteria B–D
B. Aura consisting of ≥1 of the following, but no motor weakness:
1. fully reversible visual symptoms including positive and/or
negative features
2. fully reversible sensory symptoms including positive and/or
negative features
3. fully reversible dysphasic speech disturbance
32
33. Typical aura
with migraine headache contd…
C. At least two of the following:
1. homonymous visual symptoms and/or unilateral sensory
symptoms
2. at least one aura symptom develops gradually over ≥5 min
and/or different aura symptoms occur in succession over ≥5
min
3. each symptom lasts ≥5 and ≤60 min
D. Headache fulfilling criteria B-D for 1.1 Migraine without aura
begins during the aura or follows aura within 60 min
E. Not attributed to another disorder
33
34. Complications of migraine
∗ Chronic migraine
Migraine headache that occurs more than 15 days a month for
greater than 3 months
∗ Status migrainosus
Migraine attacks persists for >72 hours.
∗ Persistent aura ( 30-60 min ) without infarction
∗ Migrainous infarction
∗ Migraine triggered seizures
34
35. Work up
∗ Migraine is a clinical diagnosis.
∗ Diagnostic investigations are performed due to following reasons
∗ Exclude structural, metabolic and causes of heada
∗ Rule out comorbid disease that could complicate headache and
its treatment
35
36. ∗ Neuroimaging is usually not necessary except
∗ Onset of migraine after 5o years of age
∗ change in the pattern of previous migraine
∗ First or worst severe headache
∗ New onset of headache in a patient with cancer or HIV patient
∗ Headache with an abnormal neurologic examination
∗ Headache with fever
∗ Migraine and epilepsy
∗ New daily persistent headache
∗ Escalation of headache frequency/intensity in the absence of
medication overuse headache
∗ Posteriorly located headaches in children
36
37. ∗ Visual field testing should be performed in patients with
persistent visual phenomenon
∗ Indications for lumber puncture include -:
1. First or worst headache of a patients life
2. Severe, rapid onset, recurrent headaches
3. Progressive headaches
4. Atypical chronic intractable headaches
37
39. General principles of management
∗ Establish a diagnosis.
∗ Educate migraine sufferers about their condition and its
treatment.
∗ Encouraging patients to track their own progress through the use
of diary cards, flow charts, headache calendars and frequency
and severity of attacks, the presence and degree of temporary
disability, and associated symptoms such as nausea and vomiting.
∗ Create a formal management plan and individualize
management. Consider comorbidity/coexisting conditions (such
as heart disease, pregnancy, and uncontrolled hypertension).
39
40. General principles of management contd..
∗ Encourage the patient to identify and avoid triggers.
∗ Guard against medication-overuse headache (“rebound
headache” or “drug-induced headache”). Frequent use of acute
medications (ergotamine [not DHE], opiates, triptans, simple
analgesics, and mixed analgesics) is generally thought to cause
medication-overuse headache.
∗ Use migraine-specific agents (triptans dihydroergotamine [DHE])
in patients with moderate or severe migraine or whose mild-to-
moderate headaches respond poorly to nonsteroidal anti-
inflammatory drugs (NSAIDs) or combinations such as aspirin plus
acetaminophen plus caffeine
40
41. Acute Treatment
Goals of acute migraine treatment are as follows:
∗ Treat attacks rapidly and consistently without recurrence.
∗ Restore the patient’s ability to function.
∗ Minimize the use of back-up and rescue medications. (A rescue
medication is used at home when other treatments fail and
permits the patient to achieve relief without the discomfort and
expense of a visit to the physician’s office or emergency
department.)
∗ Be cost-effective for overall management.
∗ Have minimal or no adverse events
41
42. Specific medications
Triptan (serotonin 1B/1Dreceptor agonists)
∗ Effective and safe
∗ acute management
∗ Appropriate initial choice in patients with moderate to severe
migraine
∗ Routes-oral, subcutaneous and nasal
∗ Drugs – sumatriptan-50-100mg tablet at onset , may repeat after
2hour (max 200mg/d)
∗ Rizatriptan –most efficacious, early onset of action, 5-10 mg
tablet at onset may repeat after 2hr max 30mg/d)
∗ Naratriptan, almotriptan,frovatriptan, zolmitriptan
42
43. Specific medications contd…
∗ Triptans should not be used more than 3 days weekly to avoid
transformed migraine and medication overuse headache
∗ Caution-avoid in patients of CAD
∗ Adverse effects
∗ Paresthesia, jaw or neck tightness, warm/cold sensation etc.
43
44. Specific medications contd…
∗ Ergot alkaloids and derivatives-nonselective 5-HT1 agonists)
∗ Ergotamine PO/PR (and caffeine combination) may be considered
in the treatment of selected patients with moderate to severe
migraine.
∗ Dose 2mg PO, f/b 1-2mg every 30 min until attack is aborted, no
more than 6mg/day
∗ Adverse effects-vasospasm, angina, tachycardia, numbness of
extremities, rebound headache, ergotism, gangrene etc
44
45. Specific medications contd…
∗ Dihydroergotamine- alpha adrenergic blocking agent with a
direct stimulating effect on smooth muscle of peripheral and
cranial blood vessels. It is a non selective 5-HT1 agonist
∗ Route- iv or nasal
∗ Dose- 1mg iv/im repeated 1 hrly , no more than 3 mg for im and
2mg for iv
∗ Nasal-1 spray 0.5mg in each nostril not more than 6 sprays/24hr
∗ DHE nasal spray is safe and effective for the treatment of acute
migraine attacks and should be considered for use in patients with
moderate to severe migraine
∗ DHE IV plus antiemetics IV is an appropriate treatment choice for
patients with severe migraine
45
46. Non specific medications
Antiemetics -:
∗Oral antiemetics are an adjunct to treat nausea associated with
migraine .
∗Metoclopramide IM/IV is an adjunct to control nausea and may be
considered as IV monotherapy for migraine pain relief
∗Prochlorperazine IV, IM, and PR may be a therapeutic choice for
migraine in the appropriate setting
∗Chlorpromazine IV
∗ Serotonin receptor (5-HT3) antagonists may be considered as
adjunct therapy to control nausea in selected patients with migraine
attacks
46
47. Non specific medications contd…
∗ NSAIDs, nonopiate analgesics, and combination analgesics.
∗ Acetaminophen, alone, is not recommended for migraine .
∗ NSAIDs (oral) and combination analgesics containing caffeine are
a reasonable first-line treatment choice for mild to moderate
migraine attacks or severe attacks that have been responsive in
the past to similar NSAIDs or nonopiate analgesics
47
48. Non specific medications contd…
∗ Opiate analgesics.
∗ Butorphanol nasal spray is a treatment option for some patients
with migraine (Grade A). Butorphanol may be considered when
other medications cannot be used or as a rescue medication when
significant sedation would not jeopardize the patient
∗ Other medications.
∗ Isometheptene and isometheptene combination agents may be a
reasonable choice for patients with mild-to-moderate headache .
∗ Corticosteroids (dexamethasone or hydrocortisone) are a
treatment choice for rescue therapy for patients with status
migrainosus .
48
49. Preventive treatment
May be considered when -:
∗ Frequency of migraine is >2/months
∗ Duration of individual attack is longer than 24hrs
∗ Headache causes major disruption in patients lifestyle
∗ Abortive therapy fails or is overused
∗ Symptomatic medications are ineffective
∗ Use of abortive medications more than twice a week
∗ Migraine variants such as hemiplegic migraine
49
50. ∗ The goals of migraine preventive therapy are to
1) reduce attack frequency, severity, and duration
2)improve responsiveness to treatment of acute attacks
3)improve function and reduce disability
50
51. Pharmacotherapy
5 principal classes of drugs are used -:
∗ Antiepileptics
∗ Antidepressants
∗ Antihypertenseives
∗ Serotonin antagonists
∗ NSAIDS
51
52. ANTIEPILEPTICS
∗ Well tolerated
∗ Valproic acid is useful as afirst line agent.400-600 mg BD
∗ Carbamazepine
∗ Gabapentin
∗ topiramate
52
53. ∗ ANTIDEPRESSANTS
∗ Tricyclic antidepressants
∗ Amitriptyline- 10-75mg at night
∗ Nortriptyline
Selective serotonin reuptake inhibitors
∗ Fluoxetine
∗ Other antidepressants
∗ Bupropion, mirtazepine, trazodone, venlafaxine
53
55. SEROTONIN ANTAGONISTS
Methysergide-1-4mg OD
∗ Flunarizine5-15mg OD
∗ NSAIDS
∗ Aspirin
∗ Mefenamic acid
∗ Ibuprofen
∗ Naproxen/naproxen sodium
∗ Other
∗ Magnesium
∗ Vitamin B2
55
56. ∗ Special considerations
∗ Direct special attention to women who are pregnant or want to
become pregnant. Preventive medications may have teratogenic
effects.
∗ Take coexisting conditions into account. Some
(comorbid/coexisting) conditions are more common in persons
with migraine.
∗ Eg-beta blocker are preferred in young anxious patients,
hypertensive patients, history of angina
∗ TCA’s are preferred in patients of depression, underweight
∗ Valproic acid is preferred in patients of epilepsy and mania
56
57. Non-pharmacological treatment
∗ Biofeedback
∗ Cognitive-behaviour therapy
∗ Relaxation therapy
∗ AVOIDANCE OF MIGRAINE TRIGGERS
∗ Complimentary and alternative therapy
∗ Body work eg. massage
∗ Creative arts eg. dance, music
∗ Yoga
∗ Acupuncture and acupressure
57