Slide 1: Recent advances in Migraine Dr. Pratheep Kottam. MBBS, MD, DM Neurology
Assistant Professor in Neurology
Department of Neurology
MOSC Kolenchery, Kochi, Kerala, India Topic will be discussed under following headings : Topic will be discussed under following headings Introduction
Treatment Slide 3: Introduction Slide 4: Definition of Migraine Primary headache
Episodic disorder with headache attacks
Highly disabling chronic progressive disorder IHS: Disorder characterized by intermittent attacks of headache combined with autonomic disturbances Epidemiology of Migraine : Epidemiology of Migraine Sources: CDC, NHANES III, NHIS, Office for National Statistics, Literature. Migraine is more common than arthritis, asthma, or diabetes Slide 6: Global Prevalence of Migraine Believed to affect up to 17% of females and 6% of males
Yet under diagnosed, under- treated & poorly understood
Represents a significant burden to society Slide 7: Disability of migraine “WHO rates severe migraine along with quadriplegia, psychosis & dementia as one of the most disabling chronic disorders.” (Archives of Neurology, 2000) Lipton RB et al. Headache. 2001;41:638-645. Functional impairment in 92% & severe impairment in 53% Slide 8: Disability of migraine… 31% patients lose at least 1 day of work & 76% lose at least 1 day of household activities every 3 months
51% report that work or school productivity is reduced by half & may decrease even more as pain intensifies Slide 9: Clinical features Slide 10: Diagnosis of migraine can be challenging
Diagnosis by exclusion
No consistent physical findings, no biological markers, relies on history alone
Previous diagnostic criteria are overlapping, confusing & inconclusive
Often misdiagnosed as tension-type headache Slide 11: Profile of migraineurs Females affected 3 times more commonly than men
Ages 22 - 55
Most productive, active years
But can affect young and elderly
Often has family history of migraine
Increased chance of suffering attacks if even one parent has migraine Slide 12: Profile of a Migraineur… Slide 13: Lipton RB, et al. Headache. 2001;41:646-657. Reproduced with permission. Profile of a migraineur… Slide 14: Clinical Characteristics 4 stages occurring in sequence, not all patients experience all stages:
Prodrome : usually precedes headache by 24 hours
Aura : typically resolves in less than 60 minutes
Headache : usually unilateral & throbbing, accompanied by nausea, vomiting, photophobia and/or phonophobia, and lasts about 4 to 72 hours
Postdrome : occurs after the attack & can last hours to days Slide 15: Four Stages of Migraine Migraine presentation is unique — as many as four stages Prodrome
Precedes by 24 hours
Physical symptoms Aura
Resolves ~60 minutes Headache
Nausea or vomiting
Photophobia and phonophobia
Persists ~72 hours Postdrome
After attack, can last hours to days
Exhaustion, or extreme happiness
Neurologic, vascular resolve Slide 16: The Migraine Experience Slide 17: Migraine is a diagnosis by history
Mostly no signs or investigational findings
Exact characterization of headache – most important
Drug history - look for rebound headache History – most important ID Migraine : ID Migraine A validated tool useful in migraine screening.
3 screening questions to identify likely migraineurs :
1. Do you have recurrent headaches that interfere with work, family, or social functions?
2. Does your headaches last at least 4 hours?
3. Have you had new or different headaches in the past 6 months?
Migraine is considered if patients reply “Yes” to the first 2 questions and “No” to 3rd question. Slide 19: Physical examination Examination may reveal
Tender scalp, nasal & paranasal sinuses, & teeth
Examination is mainly to rule out other causes of headache
Systemic diseases (hypertension, infection)
Local tenderness & fever (periostitis 20 to mastoiditis or sinusitis)
Ptosis (cluster , brain tumors or aneurysms)
Papilledema (increased ICT, expanding ICSOL)
Fever, stiff neck (meningitis or encephalitis) Slide 20: Classification Slide 21: IHS classification system: Primary headache Diagnosis of migraine based on IHS (International Headache Society) classification
Primary headache is headache not caused by another disorder
Migraine and tension-type account for 75%-90% of primary headache IHS Classification of Migraine: : IHS Classification of Migraine: Probable Migraine without aura
Migraine without aura
Probable Migraine with aura
Migraine with aura
Migraine headache + typical aura
Typical aura + Non migraine headache
Typical aura without headache
Sporadic hemiplegic Migraine
Basilar Migraine IHS Classification of Migraine… : IHS Classification of Migraine… Childhood periodic syndromes
BPPV of childhood
C/c migraine, Status migranosus
Unclassifiable migraine like disorders Cephalalgia 2004;24, S(1) Slide 25: IHS criteria: Migraine without aura >5 attacks fulfilling B to D & not due to another cause.
Duration - 4 to 72 hours
Headache has at least two of the following features:
Moderate or severe pain intensity
Aggravation by routine physical activity like walking
During headache at least one of the following:
Nausea and/or vomiting
Photophobia and phonophobia Slide 26: At least 2 attacks fulfilling at least 3 of the following
One / more aura indicating focal brain dysfunction
At least 1 aura develop gradually over > 4 minutes OR 2 or more symptoms occur in succession
Aura < 60 minutes; if more than 1 aura, duration is proportionally increased
Headache follow aura with free interval of less than 60 min (it may begin simultaneously with aura) IHS criteria: Migraine with aura Usual migraine auras: : Usual migraine auras: Homonymous visual disturbance
Unilateral paresthesias and/or numbness
Aphasia or unclassifiable speech difficulty Fortification spectra of visual auras have been compared to fortified, walled city of Palmanova, Italy : Fortification spectra of visual auras have been compared to fortified, walled city of Palmanova, Italy Artist’s representation of his visual aura. Fortification spectrum associated partial visual loss. : Artist’s representation of his visual aura. Fortification spectrum associated partial visual loss. Progressive central scotoma with a jagged edge : Progressive central scotoma with a jagged edge Motorist’s right hemianopia, scotoma surrounded by a crescentic area of brighter lights. : Motorist’s right hemianopia, scotoma surrounded by a crescentic area of brighter lights. Basilar Migraine : Basilar Migraine Children & adolescents
Severe occipital headache
Features of Basilar occlusion
Consciousness impaired - RF
Last 10 to 30 min
May leave neurologic defects
Bickerstaff’s migraine – dramatic form in females
With age replaced by migraine without aura Retinal migraine : Retinal migraine Retinal & Anterior optic nerve ischemia
Mono ocular visual disturbance followed by headache
Photopsia – flashes of light
Areas of visual loss, altitudinal defects, transient U/L blindness Ophthalmoplegic migraine : Ophthalmoplegic migraine Child with U/L orbital or retro orbital pain
Headache + Extra ocular muscle palsy
III nerve > IV nerve / VI nerve
IL ptosis progressing to complete III nerve palsy
EOM palsy last more than headache
MRI – thickening & contrast enhancement of III nerve as it leaves Midbrain
May leave permanent neurologic defects Hemiplegic migraine : Hemiplegic migraine Typical migraine with aura + motor weakness during aura
Consider only if past h/o migraine with aura is present
Typically 30 to 60 minutes - can be hours, days or weeks
Recovery usually complete
Sporadic or familial
Sporadic – side can alternate Familial hemiplegic migraine : Familial hemiplegic migraine Usually same side in each attack
Chromosome 19 (CACNL4 gene) and 1
Volt gated P/Q Ca Channelopathy
+/- Cerebellar signs
Acetazolamide to Dec frequency – unproven
? IV Verapamil Childhood migraine : Childhood migraine IHS classification allows diagnosis of childhood migraine for headaches with fewer features.
Attacks are shorter than in adults
Throbbing quality or unilaterality, photophobia and phonophobia, are less common.
Childhood periodic syndromes - cyclical vomiting, abdominal migraine, and benign paroxysmal vertigo of childhood Slide 38: Pathophysiology Pathophysiology : Pathophysiology Theories of migraine pathophysiology have traditionally fallen into two categories:
2. Neurogenic Classic vascular theory : Classic vascular theory Aura caused by intracranial vasoconstriction
Headache results from subsequent rebound vasodilatation
Theory emerged because:
superficial temporal artery pulsations increased in amplitude with increased throbbing quality of pain
Ergotamine, a vasoconstrictor, relieved pulsations of the superficial temporal artery and the pain Slide 41: Vascular theory… Slide 42: Physical stress Emotional shockPsychic stress AllergyHormonal imbalance etc. Cerebral hypoxia: the core of “migraine vicious circle” BiochemicalchangesHaematologicalchangesVascularchanges Reactivevasodilatationinducesmigraineattack O2supply O2demand Localizedbrain cellhypoxia Cerebralvasocon-striction andneuronalhyperactivity Slide 43: During cerebral hypoxia calcium overload has been demonstrated clinically and experimentally in:
Red blood cells - increased blood viscosity.
Contractile elements of vascular endothelium, smooth muscle in vascular walls – vasoconstriction
Brain cells - neuronal damage.
In migraine there is synergism of all these factors and a vicious cycle is established Cerebral hypoxia Slide 44: Cerebral Hypoxia
Reactive Vasodilatation of Cerebral Vessels
Migraine Attack Neurogenic theory of migraine : Neurogenic theory of migraine Migraine is due to 10 neuronal dysfunction & vascular changes are only 20.
Aura is characterized by a wave of oligemia that passes across the cerebral cortex at a rate of 2 mm to 6 mm per minute - cortical spreading depression
Actually spreading activation followed by spreading depression – respect anatomical boundaries, not arterial boundaries
Oligemia is a response to depressed neuronal function Trigeminal-vascular complex : Trigeminal-vascular complex Neurogenic inflammation triggered by Trigeminal sensory system
Triggered by spreading activation / depression
Mediated by Substance P & Calcitonin gene related peptide (CGRP)
Trigeminal nucleus caudalis (TNC) & ophthalmic branch of V n important
Evidence of platelet aggregation & Serotonin release in migraine attack
Role of Serotonin indirectly seen by drug action Slide 47: Neurovascular Theory A stimulus triggers neural events in brainstem
This results in dilation of blood vessels & release of inflammatory neuropeptides
This stimulate nerves around these blood vessels
This nerve involvement sends an impulse through the trigeminal nerve into trigeminal nucleus caudalis.
From there it is relayed to the thalamus, where pain is processed
From Thalamus to cortex, then to outer layer of brain, where the nerve signals actually become clinical pain Other concepts : Other concepts Dec brain energy metabolism - mitochondrial abnormality
Systemic & brain Mg deficiency
Gain of NMDA receptor function
Brainstem/Hypothalamic generator – MB stimulation near dorsal raphe induces migraine
Central sensitization – abnormality in central pain processing
Empty neuron hypothesis – genetically mediated inability to maintain normal levels of NT in post ganglionic sympathetic terminals Summary : Summary Migraineurs have a susceptibility to spontaneous depolarization & neuronal hyper excitability
Followed by prolonged hypo metabolism due to mitochondrial defect & Mg deficiency
Secondary vascular changes contributing to throbbing & pain Slide 50: Investigations Are investigations needed ? : Are investigations needed ? Always rule out dangerous differential diagnoses when
- history is not typical
- uncommon migraine variants are being considered
- when response to treatment is inadequate
- when a new type of headache emerges in a patient with migraine Does this patient with headache need imaging? : Does this patient with headache need imaging? 11 studies (n=3,725), were included.
Prevalence of abnormality on imaging ranged from 1.2% in c/c headache to 43% in thunderclap headache. Cochrane – structured abstract - 2006 Clinical features predictive of intracranial abnormality : Clinical features predictive of intracranial abnormality Headache with aura
Headache aggravated by exertion or valsalva
Headache with vomiting
Undefined i.e. not cluster, migraine or tension type
Abnormal neurologic examination Cochrane 2006 Clinical features that were not useful in predicting intracranial abnormality : Clinical features that were not useful in predicting intracranial abnormality Headache with focal symptoms
Worsening of headache
Quick on-set headache
New on-set headache
Headache with nausea
Increased headache severity
Migraine-type headache Cochrane 2006 Clinical features with negative predictor value : Clinical features with negative predictor value Headache not aggravated by valsalva
Absence of vomiting
Headache of defined type.
BUT – No clinical feature was useful for completely ruling out serious intracranial abnormality. Cochrane 2006 PET in migraine - activation of rostral brainstem structures : PET in migraine - activation of rostral brainstem structures PET in cluster – activation of posterior hypothalamic grey matter : PET in cluster – activation of posterior hypothalamic grey matter PET in experimentally headache – no typical findings : PET in experimentally headache – no typical findings Slide 59: Treatment Advertisement from a US magazine (Harper’s), 1863. : Advertisement from a US magazine (Harper’s), 1863. Headache gone after Wolcott’s treatment : Headache gone after Wolcott’s treatment Slide 62: Treatment Acute or abortive therapy
Long-term preventive or prophylactic treatment
Trigger factor modification
Non pharmacologic measures
Recent advances Slide 65: Acute Therapy DEFINITION: medications taken after migraine attack begins to reduce duration & severity of attack. Often targets blood vessels. Slide 66: IHS guidelines for acute therapy Educate & encourage migraineurs to participate in management
After NSAIDs, use triptans, DHE (Dihydroergotamine) or ergotamine in patients with severe migraine or in poor NSAID responders
Use non-oral route in patients with nausea & vomiting
Consider a self-administered rescue medication
Guard against medication-overuse headache Slide 68: Acute Therapy: Pros and Cons POSITIVES:
Rapid onset of action
Ideal for occasional migraine
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 rebound headache Acute Therapy : Acute Therapy Start Rx at the earliest
Exception – sc Sumatriptan act best after onset of headache
Oral drugs less effective once attack begin – vomiting, Dec GI motility & absorption
Sleep in a dark, quiet room with ice pack over head
NSAIDS+ Caffeine + Metoclopromide 10 mg Triptans : Triptans Selective 5HT agonists
Benefit headache & associated symptoms
Triptans ineffective in migraine with aura till aura is over & headache begins
After one Triptan, another Triptan or ergot is CI for 24 hours
SE – Flushing, neck / chest pressure Mechanism of action of Triptans : Mechanism of action of Triptans Stimulation of the 5-HT1B/D receptors.
5-HT1B receptor stimulation cause cranial vaso-constriction
Selective for cerebral blood vessels since peripheral vasoconstriction is mediated by 5-HT2 receptors.
5-HT1D receptors on 1st & 2nd order trigeminal neurons decrease release of neuropeptides mediating vaso-dilation & activity of pain-signalling neurons Triptans contraindications : Triptans contraindications CAD
Hemiplegic or Basilar migraine
Avoid in those on Ergots, SSRI & TCA
Should not use more than 2 days a week to decrease possible rebound headaches. 7 Triptans : 7 Triptans Sumatriptan
Almotriptan – fast acting
Frovatriptan – slow acting & lowest efficacy Sumatriptan : Sumatriptan 6 mg sc
25 to 100 mg orally
20 mg nasal spray Oral Sumatriptan for a/c migraine : Oral Sumatriptan for a/c migraine 25 trials - 16,200 participants
Placebo comparisons -16 trials - showed that sumatriptan in doses of 100 mg (14 trials), 50 mg (5 trials), and 25 mg (3 trials) provided significantly better pain relief at 2 hours.
Adverse events were more common with sumatriptan 100 mg than with placebo Cochrane Review - 2011 Oral sumatriptan - Authors’ conclusions : Oral sumatriptan - Authors’ conclusions Oral sumatriptan is an effective drug for treatment of a single acute attack of migraine.
It is well tolerated, though minor adverse events were not uncommon in included trials.
Other triptans - similar in efficacy & adverse events.
Among non-triptan drugs, ergotamine + caffeine was significantly less effective than sumatriptan, and other drugs have been insufficiently studied Cochrane Review - 2011 Rizatriptan : Rizatriptan Fast acting
10 mg PO
10 mg dissolvable wafer
Rizact Naraitriptan : Naraitriptan Slow acting & lowest efficacy
Study – Useful in Menstrual migraine
1 or 2.5 mg PO
Naraitrex Zolmitriptan : Zolmitriptan 2.5 mg PO
Dispersible tablets also – 2.5 mg
5 mg nasal spray Caffeine : Caffeine Aids absorption
Dec firing of serotonergic brainstem neurons
Not to be taken > 2 times / week – Increase headache frequency
Caffeine addiction/withdrawal headache may occur Ergots : Ergots Vasoconstrictor
5HT agonist – similar to triptans
But more adverse effects due to binding at non-5HT1 receptors, dopaminergic & adrenergic receptors.
Dose – 2 mg immediately – can repeat after 1 hour
Rectal or Parenteral better than oral
Combine with NSAIDS + Caffeine
Slower action than Triptans but lesser recurrence Ergots… : Ergots… Inc nausea – combine with antiemetics
Maximum 6 mg / week – otherwise withdrawal headache
Caution – HTN, PVD, Prolonged aura or aura with major CNS deficits
CI – Pregnancy, CAD, Concurrent use of phenyl propranolamine Steroids - dexamethasone addition to standard therapy for a/c migraine : Steroids - dexamethasone addition to standard therapy for a/c migraine 7 RCTs (n=742)
Dexamethasone vs. placebo (both + standard therapy): Dexa group was less likely to experience recurrent headache within 24 to 72 hours.
Authors' conclusions - moderately effective at preventing headache recurrence when used in addition to standard treatment of a/c migraine. Side effects are mild and transient Cochrane - 2008 Intranasal Lidocaine : Intranasal Lidocaine Absorption of oral drugs inadequate in acute migraine
Intranasal Lidocaine provided rapid and effective relief of pain in ~ 55% of patients
Most of the effect occurred within 5 minutes, & nausea and photophobia were similarly relieved.
BUT - 42% had relapse - comparable with sumatriptan
The onset of relapse with Lidocaine, however, was within 1 hour. Normobaric & hyperbaric oxygen for migraine : Normobaric & hyperbaric oxygen for migraine 9 small trials involving 201 participants
Trials suggest that HBOT is effective in relieving migraine headaches compared to sham therapy.
No evidence that HBOT could prevent migraine episodes, reduce nausea & vomiting or reduce use of rescue medication.
No serious adverse effects of HBOT or NBOT were reported. Cochrane review 2009 NBOT & HBOT - Authors’ conclusions : NBOT & HBOT - Authors’ conclusions There was some evidence that HBOT was effective in a/c migraine in an unselected group
Given the cost and poor availability of HBOT, more research should be done on patients unresponsive to standard therapy.
NBOT is cheap, safe and easy to apply, so will probably continue to be used despite limited evidence. Cochrane review 2009 Other drugs in acute therapy : Other drugs in acute therapy Narcotics – nasal Butorphanol
Isometheptene Acute treatment of migraine. Breaking the paradigm of monotherapy : Acute treatment of migraine. Breaking the paradigm of monotherapy Evidences support use combination of drugs acting on different mechanisms in acute migraine
Whom to use
- patients not achieving pain-free status in 2 hours or not getting sustained pain relief for 24 hours in 5 previous migraine attacks
What to use
- combination of NSAID plus a Triptan or a gastro kinetic drug such as 20 mg Metoclopromide or 30 mg domperidone BMC Neurology Slide 89: Preventive Therapy Patients qualify for preventive treatment if:
Recurring migraine significantly interferes with daily routine
Frequent attacks (2 or more migraines per month with disability totaling 3 or more days)
Acute medications are used more than 2 times per week
Acute medications are contraindicated, not tolerated, or ineffective Preventive Therapy: Is it needed ? : Preventive Therapy: Is it needed ? Migraine is a chronic and progressive disease
Delay in initiating appropriate treatment may hasten the development of central sensitization within and between attacks.
This can lead to progression from episodic migraine to chronic migraine in 5% patients. JAOA • Supplement 2 • Vol 105 • No 4 • April 2005 - Advances in Migraine Treatment - George R. Nissan et. al Preventive Therapy - components : Preventive Therapy - components Trigger factor modification
Non pharmacologic measures
Pharmacologic measures Slide 92: Migraine Triggers Migraine triggers present in up to 85% of patients
Average number of triggers is 3/patient
Weather changes, smoke, bright lights, certain smells)
Emotions (stress, anxiety, crying)
Change in sleep pattern
Diet - cheese, redwine, chocolate, nitrates
Estrogen (menstrual cycle) Trigger factor modification : Trigger factor modification Identify and then avoid trigger factors such as
Avoid irregular sleep pattern
Avoid prolonged fasts
Avoid irregular sleep
Anti glare measures
Avoid strong perfumes
Acute changes in stress levels
Avoid certain foods (chocolates, cheese) Avoid drugs causing headaches : Avoid drugs causing headaches Reserpine
Steroid withdrawal Slide 95: Behavioral Modification Slide 96: Classes of Agents Used for Preventive Therapy Calcium channel blockers
Propranolol and Timolol
Tricyclic antidepressants (TCA)
Nortriptyline AEDs (also called "Neurostabilizers")
Divalproex sodium/Valproate semisodium
Time-released dihydroergotamine Calcium channel antagonists : Calcium channel antagonists Flunarizine
Indicated in classical & common migraine.
Dose :10 mg/d. In patients weighing <40 kg & elderly : 5 mg/d.
SE – somnolence, fatigue, and weight gain
Adverse reactions are usually transient. Flunarizine -Mechanism of Action : Flunarizine -Mechanism of Action Ca++ entry blocker : Via Ca channels in cell membrane
No effect on voltage operated Ca channels in heart.
Protects RBCs against Ca overload
Protects vascular smooth muscle from Ca overload
Prevents vascular constriction
Protects brain cells against Ca overload & subsequent brain cell damage. Slide 99: Within first four weeks migraine frequency reduces
Decrease in migraine frequency develops gradually over the first three months of therapy.
Patients continue to experience relief for several months after 6-9 months of treatment.
Flunarizine has better safety profile than Propranolol Flunarizine - role in migraine prophylaxis Beta blockers : Beta blockers Propranolol
– 80 to 240 mg / day
- LA better
Timolol, Nadolol, Atenolol, Metoprolol Propranolol for migraine prophylaxis Cochrane Review - 2009 : Propranolol for migraine prophylaxis Cochrane Review - 2009 58 trials (n= 5072) met inclusion criteria.
Most studies were of poor quality
26 placebo-controlled trials showed clear short-term effects of Propranolol over placebo.
47 comparisons with calcium antagonists, other beta-blockers, and a variety of other drugs did not yield any clear-cut differences. Cochrane Review - 2009 Propranolol - Author’s conclusions : Propranolol - Author’s conclusions Although many trials have shortcomings, there is clear evidence that Propranolol is more effective than placebo in short-term treatment of migraine.
Evidence on long-term effects is lacking.
Propranolol seems to be as effective and safe as other drugs used for migraine prophylaxis. Cochrane Review - 2009 Tricyclic antidepressants : Tricyclic antidepressants Independent of antidepressant action
Amitryptiline – 10 to 150 mg HS
Anticholinergic side effects Anticonvulsants for migraine prophylaxis : Anticonvulsants for migraine prophylaxis Divalproex sodium – 500 to 1750 mg/day
Topiramate – 70 to 200 mg / day
Gabapentin – 600 to 2400 mg / day Topiramate : Topiramate FDA approval in 2004
Trials – reduce attacks by 50% & well tolerated.
Start at 25 mg, increase by 25 mg/ week to 100-200 mg
SE – usually transient and mild
Acute glaucoma - rare
Renal colic may exacerbate
Category C drug in pregnancy
Can decrease OCP efficacy Anticonvulsants for migraine prophylaxis (Cochrane Review 2009) : Anticonvulsants for migraine prophylaxis (Cochrane Review 2009) 23 papers met inclusion criteria - 2927 patients
10 trials (n = 902) shows that AEDs reduce migraine frequency by 1.3 attacks/ 28 days
13 trials (n = 1773) show that AEDs more than doubles the number of patients for whom migraine frequency is reduced by 50% or more Cochrane Review 2009 AEDs - authors’ conclusions : AEDs - authors’ conclusions AEDs appear to be effective & well tolerated.
Variation among individual agents, but insufficient data.
Robust trials are available only for Na valproate, Divalproex sodium and topiramate
Acetazolamide, Clonazepam, Lamotrigine, Vigabatrin were not superior to placebo.
Gabapentin needs further evaluation. Cochrane Review 2009 Serotonergic agents : Serotonergic agents Methysergide
Block peripheral 5 HT actions
All types of vascular headache
Only for intractable – max 6 months
Peripheral Serotonin antagonist
More effective in children Slide 109: Maintain headache diaries – can document effect or lack of it
Formal disability scales can be used
MIDAS (Migraine Disability Assessment Scale) can quantify the disability MIDAS (Migraine Disability Assessment Scale) : MIDAS (Migraine Disability Assessment Scale) About headaches in last 3 months.
1 How many days did you miss work due to headaches?
2 How many days productivity at work was reduced due to headaches? (Do not include days counted in 1)
3 How many days you did not do household work due to headaches?
4 How many days was your productivity in household work reduced by half or more due to headaches? (Do not include days counted in 3)
5 On how many days in the last 3 months did you miss family, social or leisure activities due to headaches?
TOTAL days - Grading system for MIDAS Questionnaire: : Grading system for MIDAS Questionnaire: Grade Definition Score
I - Little or no disability 0–5
II - Mild disability 6–10
III - Moderate disability 11–20
IV - Severe disability 21+
A On how many days in the last 3 months did you have a headache? (If a headache lasted more than 1 day, count each day)
B On a scale of 0–10, on average how painful were these headaches? (Where 0 = no pain at all, and 10 = pain as bad as it can be) Recent Advances : Recent Advances CGRP antagonists : CGRP antagonists Calcitonin gene-related peptide - CGRP
Important pathophysiological role in migraine
Potent vasodilator released from trigeminal -vascular system during migraine
Levels raised during & immediately after migraine attack
No direct vasoconstrictor activity – so safe in CAD N Engl J Med 2004;350:1104-10. CGRP antagonists in trial : CGRP antagonists in trial BIBN4096BS effective in treating acute migraine – 2.5 mg
Olcegepant – IV
Telcagepant – oral 300 mg NXN 188 : NXN 188 Under study for acute migraine
Neuronal Nitric oxide synthase enzyme inhibitor Single pulse transcranial magnetic stimulation in acute migraine - sTMS : Single pulse transcranial magnetic stimulation in acute migraine - sTMS A device delivers a pulse transcranial magnetic stimulation at the onset of headache or aura
Idea is to disrupt cortical spreading depression by application of sTMS at the onset of aura
Lipton et al reported promising results in their study Migraine prophylaxis with oral magnesium : Migraine prophylaxis with oral magnesium 81 patients (18-65 years) with migraine received oral trimagnesium dicitrate 600 mg/d for 12 weeks or placebo.
In weeks 9-12 attack frequency was reduced by 41.6% in magnesium group and by 15.8% in placebo group compared to baseline (p < 0.05).
Adverse events - diarrhea (18.6%) & gastric irritation (4.7%)
High-dose oral Mg appears to be effective in migraine prophylaxis Cephalalgia. 1996 Jun;16(4):257-63 Acupuncture for migraine prophylaxis : Acupuncture for migraine prophylaxis 22 trials (4419 patients) met inclusion criteria.
Acupuncture vs. no prophylaxis - 6 trials
After 4 months acupuncture patients had higher response rates and fewer headaches.
True acupuncture vs. sham interventions – 14 trials - did not show significant superiority
Acupuncture vs. proven prophylactics – 4 trials Acupuncture had slightly better outcomes & fewer adverse effects than prophylactic drugs. (Cochrane Review - Linde K et. al – 2009) Acupuncture - Authors’ conclusions : Acupuncture - Authors’ conclusions There is evidence that acupuncture is better than treatment of a/c migraine only or to routine care.
Available studies suggest that acupuncture is at least as effective as, or possibly more effective than, prophylactic drugs, & has fewer adverse effects.
Acupuncture should be considered a treatment option for willing patients (Cochrane Review - Linde K et. al – 2009) Biofeedback for migraine: : Biofeedback for migraine: 55 studies (n=2,229) were included
Medium statistically significant effect on headache compared with baseline
Follow-up studies (15 studies). Medium-to-large statistically significant effect on headache
No significant differences BFB modalities
Authors' conclusions - medium short- and long-term effect, reducing pain & psychological symptoms Cochrane meta-analysis - 2007 Cochrane Review & meta-analysis of evidence on migraine & PFO closure : Cochrane Review & meta-analysis of evidence on migraine & PFO closure Studies underway to look for effect of PFO closure in preventing Migraine
Migraineurs were found to have PCA emboli during attacks
Since both Migraine & PFO being common – cause and effect yet to be established Botulinum toxin type A and c/c migraine : Botulinum toxin type A and c/c migraine Botulinum toxin type A injected symmetrically into the glabellar, frontalis, and temporalis muscles.
May reduce the local release of nociceptive neuropeptides.
Postulated to decrease release of CGRP
Also, it is postulated that the nerves may be stimulated by the strong contraction of the corrugator supercilii and the temporalis muscles. Botulinum toxin A for prophylaxis of episodic migraine - metaanalysis : Botulinum toxin A for prophylaxis of episodic migraine - metaanalysis 8 RCTs - n=1,601
No statistically significant benefit
Authors' conclusions - Botulinum toxin A was not significantly different from placebo for episodic migraine prophylaxis. Cochrane 2009 Occipital nerve stimulation : Occipital nerve stimulation Used in patients with intractable migraine
Controlled observations of occipital nerve stimulation in chronic migraine are extremely promising. Slide 125: The future for migraine treatment seems bright as the understanding of the disease is improving and newer & safer treatments are in the offing. Thank you : Thank you