Download AHD Dr. Vieira`s presenation Nov 25

INTERNATIONAL CLASSIFICATION
of
HEADACHE DISORDERS
2nd edition
(ICHD-II)
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
Headache:
a clinical tour
for residents (part 1)
November 2009
Lucy Vieira MD
©International Headache Society 2003/4
Introduction
Headache: 2 major categories
– Primary: migraine, TTH, TACs, other
– Secondary: all major categories covered
Incidence of migraine
Peak Incidence males
•Migraine with aura:
5yo (6.6/1000)
Peak incidence females
Migraine
with aura:
12-13yo
(14/1000 person-years)
without aura:
14-17yo
(19/1000 person-years)
•Migraine without
aura:
10-11yo(10/1000)
Migraine
* After age 10 i girls>boys
Stewart et. al. 1993. Amer J Epidemiol 34:1111-20
– the reported age of migraine incidence in a prevalence study
Prevalence of Migraine
•Prevalence highest from 25-55 yo.
•Prevalence is stable over time.
•After age 55 prev. starts to decrease – CDH or remission
American migraine study-I- info from 15,000 homes in 1989
AMS-II – 1999. AMPP – 2005.
prevalence mig: 18%F
(12% adults)
6%M
Lipton Headache 38:87-96 1998. Lipton Headache 41:646-57. Lipton Headache 45:792 2005
How Migraine Stacks Up Against
Other Common Diseases
12%
Affected Americans:
7%
5%
6%
1%
Rheumatoid
arthritis
Asthma
Diabetes
Osteoarthritis
Migraine
From the Centers for Disease Control and Prevention, the US Census Bureau,
and the Arthritis Foundation.
Burden of Migraine
Individual: 25% of female migraineurs have>4 severe attacks/m
(need bed rest)
Societal: loss of work productivity (13 billion/y)
- healthcare use: 4% of all visits for headache
-accounts for 1/3 of all OTC analgesic use.
Lipton 2001 Headache 41: 638-45. Hu 1999 Arch Intern Med 159:813-18. Holmes 2001
Neurology 56(s 1):13-19
Diagnosis

Patient meeting criteria for migraine
– 56% migraine
– 39% sinus diagnosis
– 31% tension headache
– 7.5% sick headache
– 10% cluster headache
AMPP 2005
TTH
Overall prevalence is 38% (F=M)
3-4X more common than migraine
Low Burden and don’t consult MD
Peak Prevalence: 30-39
Cluster Headache
80% episodic
Prevalence: 0.06-0.4%
Male>>female (3:1)
CDH
4% of the population
-in clinic: most are probable chronic migraine with MOH
-in general pop may have CTTH
(Bahra etal.2002 Neurology,58,354-361
Co-Morbidity of Migraine
(greater than co-incident association)
Depression (OR 2.5)
 Anxiety (OR 2.7)
 Epilepsy, Bipolar disease, Restless leg
syndrome
 MA: White matter lesions – esp post fossa
 MA: PFO, ASA

Scher Ann et al., Curr Opin Neurol 18:305-310
INTERNATIONAL
INTERNATIONAL
CLASSIFICATION
CLASSIFICATION
of
of
HEADACHE DISORDERS
HEADACHE DISORDERS
2nd
edition
(ICHD-II)
2nd
edition
(ICHD-II)
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Classification
Part 1:
Primary headache disorders
Classification
Part 2:
Secondary headache disorders
Part 3:
Cranial neuralgias, central and primary
facial pain and other headaches
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Classification
Part 1: The primary headaches
1. Migraine
Classification
2. Tension-type headache
3. Cluster headache
and other trigeminal autonomic cephalalgias
4. Other primary headaches
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Classification
Part 2: The secondary headaches
5. Headache attributed to head and/or neck
trauma Classification
6. Headache attributed to cranial or cervical
vascular disorder
7. Headache attributed to non-vascular
intracranial disorder
8. Headache attributed to a substance or its
withdrawal
9. Headache attributed to infection
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Classification
Part 2: The secondary headaches
10.Headache attributed to disorder of
homoeostasis
Classification
11. Headache or facial pain attributed to
disorder of cranium, neck, eyes, ears, nose,
sinuses, teeth, mouth or other facial or
cranial structures
12. Headache attributed to psychiatric
disorder
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Classification
Part 3: Cranial neuralgias, central
and primary facial pain and other
Classification
headaches
13. Cranial neuralgias and central causes of
facial pain
14. Other headache, cranial neuralgia, central
or primary facial pain
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
1. Migraine
1.1 Migraine without aura
1.2 Migraine with aura
1. Migraine
1.3 Childhood periodic
syndromes that are
commonly precursors of migraine
1.4 Retinal migraine
1.5 Complications of migraine
1.6 Probable migraine
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
1.1 Migraine without aura
A. At least 5 attacks fulfilling criteria B-D
B. Headache attacks lasting 4-72 h (untreated or
unsuccessfully treated)
C. Headache has 2 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, climbing stairs)
D. During headache 1 of the following:
1. nausea and/or vomiting
2. photophobia and phonophobia
E. Not attributed to another disorder
1.1 Migraine without aura
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
1.1 Migraine without aura
Notes
• If <5 attacks but criteria B-E otherwise met, code as
1.6.1 Probable migraine without aura
• When attacks occur on 15 d/mo for >3 mo, code as
1.1 Migraine without Notes
aura + 1.5.1 Chronic migraine
• Pulsating means varying with the heartbeat
• In children:
– attacks may last 1-72 h
– occipital headache requires caution
• In young children:
– photophobia and/or phonophobia may be inferred
from their behaviour
1.1 Migraine without aura
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
1.5.1 Chronic migraine
New entrant to classification
1.5.1
Chronic
migraine
A. Headache fulfilling criteria C and D for
New
entrant
classification
1.1
Migraine
withoutto
aura
on 15 d/mo for >3 mo
B. Not attributed to another disorder
New proposed definition: Headache on>15 days per
month and >8days per month meeting criteria for 1.1
or 1.2 or responding to migraine specific treatment
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
1.2 Migraine with aura
1.2.1 Typical aura with migraine headache
1.2
Migraine
auraheadache
1.2.2
Typical
aura with with
non-migraine
1.2.3 Typical aura without headache
1.2.4 Familial hemiplegic migraine (FHM)
1.2.5 Sporadic hemiplegic migraine
1.2.6 Basilar-type migraine
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
RARE INHERITED MIGRAINE SYNDROMES - AD
GENE
PROTEIN
RESULT
FHM-1
CACNA1A
P/Q Ca2+
channels
↑ presynaptic
Ca2+
FHM-2
ATP1A2
Na+/K+ATPase
↓ K+ and
glutamate
clearance
FHM-3
SCN1A
Na+
channel
Persistent Na+
influx
1. Sanchez del-Rio M et al. Curr Opin Neurol. 2006;19:294–298.
2. Pietrobon D. Neurotherapeutics. 2007;4:274–284.
1.2.1 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
1.2.1 Typical aura
with migraine headache
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
1.2.1 Typical aura
with migraine headache
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
1.2.1 Typical aura
with migraine headache
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
1.2.6 Basilar-type migraine
As 1.2.1 except:
B. Aura consisting of 2 of the following fully reversible
symptoms, but no motor weakness:
1. dysarthria; 2. vertigo; 3. tinnitus; 4. hypacusia;
5. diplopia; 6. visual symptoms simultaneously in both
temporal and nasal fields of both eyes; 7. ataxia;
8. decreased level of consciousness;
9. simultaneously bilateral paraesthesias
1.2.6 Basilar-type migraine
C. At least one of the following:
1. at least one one aura symptom develops gradually over
5 min and/or different aura symptoms occur in
succession over 5 min
2. each aura symptom lasts 5 and 60 min
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Childhood Periodic Syndromes
Dx
N&V
Cyclic
vomiting
+
Abd.
migraine
+/-
BPV
childhood
+
Abd.
Pain
Vertigo Duration
1h-5d
+
1-72h
+
Mins-hrs
2. Tension-type headache
2.1 Infrequent episodic tension-type headache <1/m
Tension-type
headache
2.2 2.
Frequent
episodic tension-type
headache 1-15/m
2.3 Chronic tension-type headache >15/m
2.4 Probable tension-type headache
No Nausea or vomiting!
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
3. Cluster headache
and other trigeminal autonomic
3. Cluster
headache
cephalalgias
and other trigeminal
3.1 Cluster headache
autonomic
3.2 Paroxysmal hemicrania
cephalalgias
3.3 Short-lasting unilateral neuralgiform
headache attacks with conjunctival injection
and tearing (SUNCT)
3.4 Probable trigeminal autonomic cephalalgia
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
3.1 Cluster headache
A. At least 5 attacks fulfilling criteria B-D
B. Severe or very severe unilateral orbital, supraorbital
and/or temporal pain lasting 15-180 min if untreated
C. Headache is accompanied by 1 of the following:
1. ipsilateral conjunctival injection and/or lacrimation
2. ipsilateral nasal congestion and/or rhinorrhoea
3. ipsilateral eyelid oedema
4. ipsilateral forehead and facial sweating
5. ipsilateral miosis and/or ptosis
6. a sense of restlessness or agitation
D. Attacks have a frequency from 1/2 d to 8/d
E. Not attributed to another disorder
3.1 Cluster headache
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Case
• 37 yo male with 3 yr hx HA. 6-8/d
• Severe stabbing with ipsilateral lacrimation, nasal
stuffiness. Lasts 20 min. Normal exam and
investigations.
• Seen by 3 prior neurologists.
• Failed Sumatriptan, O2, DHE, Verapamil,
Methysergide, valproic acid, Lithium.
• You see him and he is headache-free within 48 h
of new treatment!
3.2 Paroxysmal Hemicrania

Unilateral attacks lasting 2-30 minutes

Accompanied by at least one of the following:
–
–
–
–
–
1.
2.
3.
4.
5.
ipsilateral
ipsilateral
ipsilateral
ipsilateral
ipsilateral
conjunctival injection and/or lacrimation
nasal congestion and/or rhinorrhoea
eyelid oedema
forehead and facial sweating
miosis and/or ptosis

Attacks have a frequency > 5/day most of the time

Attacks are prevented completely by therapeutic doses
of indomethacin
Short Lasting Unilateral Neuralgiform headache
attacks with Conjunctival injection and Tearing
(SUNCT)
Attacks of unilateral periorbital or temporal
stabbing or pulsating pain lasting 5sec4min
 Ipsilateral conjunctival injection and
lacrimation
 Attack frequency from 3-200/day.

Differentiating features of SUNCT and trigeminal neuralgia
Feature
SUNCT
Trigeminal
neuralgia
_______________________________________________________
Sex ratio (M:F)
2:1
1:2
Site of pain
V1
V2/3
Severity of pain
Mod. to severe
Very severe
Duration (seconds)
5–250
<1
Autonomic features
Prominent
Sparse or none
Refractory period
Absent
Present
Carbamazepine response Partial
Complete
________________________________________________________
Matharu MS, Goadsby PJ. J Neurol Neurosurg Psychiatry 2002;72(suppl 2):ii19–ii26.
4.1 Primary Stabbing Headache





A. Head pain occurring as a single stab or a
series of stabs and fulfilling criteria B-D
B. Exclusively or predominately felt in the
distribution of the first division of the trigeminal
nerve.
C. Stabs last for up to a few seconds and recur
with irregular frequency ranging from one to
many per day
D. No accompanying symptoms
E. Not attributed to another disorder.
4.7 Hemicrania continua
(new entrant to the classification)

All of the Following:
1. Unilateral moderate pain.
2. Daily and continuous, without pain-free
periods.
3. Exacerbations of severe pain.

During exacerbations ipsilateral >1:
1. Conjunctival injection and/or lacrimation
2. Nasal congestion and/or rhinorrhoea
3. Ptosis and/or miosis

Complete response to indomethacin.
Hemicrania Continua
Not included in the TACs:
neuroimaging shows
activation of both areas
related to migraine and
cluster headache.
Matharu MS, et al., Posterior hypothalamic and
brainstem activation in hemicrania continua. Headache
2004; 44: 747–61.
Distinguishing TACs and
related headaches
Short Duration Headaches
I__1sec______1min_____4min__________15min____________30min_______45min_I……....I__24h
↑
Primary Stabbing Headache (sec)
↑
Trigeminal Neuralgia (sec-2min)
↑
SUNCT (5sec-4min)
↑
SUNA (2sec-10min)
↑
Paroxysmal Hemicrania (2min-30min)
↑
Cluster Headache (15min-180min)
……………
↑
Migraine (4 to 72 hr)
Short lasting and/or unilateral headache
Headache
duration frequency
autonomic
treatment
Type
attacks
features
----------------------------------------------------------------------------------------Cluster
15-180 1-3/d
+++
various
min.
CPH
2-30
5+/d
var.++
indomethacin
min.
SUNCT
secfew-50
++
lamictal?
min
PSH
sec
var
none
indomethacin
HC
contin./
many jabs
+
indomethacin
TGN
jabs
sec
many
none
carbamazepine
Autonomic Features
Manjit S. Matharu, et al.,Drugs 2003; 63 (16): 1637-1677
Primary short-lasting headaches (<4h)
Prominent autonomic features
Cluster headache
Paroxysmal hemicrania
SUNCT syndrome
Sparse or no autonomic features
Trigeminal neuralgia
Idiopathic stabbing headache
Cough headache
Benign exertional headache
Benign sex headache
Hypnic headache
SYMPTOMATIC TACS:
You should always consider
investigating TACs!
Associated pathologies in 40 TAC-like cases








Vascular diseases
Inflammatory diseases
Infectious diseases
Intracranial tumours
Extracranial tumours
Malformations
Post-traumatic
Miscellaneous
Trucco et al., Cephalalgia 24 (3), 173-184.
CPH
4
3
1
7
2
1
1
3
HC
0
0
2
1
0
0
5
1
SUNCT
1
0
1
0
0
4
0
1
CONCLUSIONS
Consider MRI of the brain in most patients who
present with rarer TAC syndromes.
Always proceed to imaging if:
1. Abnormal neurological exam
2. Clinical symptoms are atypical – do not fit
strict criteria.
3. Older age at onset
4. Insufficient response or need for prolonged
high dose therapy with indomethacin in CPH or
HC
Giraud, et al., Cluster-like Headache: literature review. J. Headache and Pain 2002,3:71-8
4. Other primary headaches
4.1 Primary stabbing headache
4.2 Primary cough headache
4.34.Primary
exertional
headache
Other
primary
headaches
4.4 Primary headache associated with sexual
activity
4.5 Hypnic headache
4.6 Primary thunderclap headache
4.7 Hemicrania continua
4.8 New daily-persistent headache (NDPH)
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
4.5 Hypnic Headache
A. Dull headache fulfilling criteria B-D
B. Develops only during sleep and awakens patient
C. >2 foll. Present:
A. occurs>15/m
B. Lasts>15 min after waking
C. First occurs after age 50
D. No autonomic S/S and no more than one of nausea,
photo/phono
E. Not attributed to another disorder
4.6 Primary thunderclap Headache
• Sudden onset with max intensity <1min
• Lasts 1h-10d
• Doesn’t recur regularly over subsequent
weeks or months
• Not attributed to another disorder
Always make sure that there is no
underlying cause!
DDX TCH:
• Aneurysmal subarachnoid hemorrhage or
other ICH
• Carotid or vertebral artery dissection
• CVST
• Pituitary apoplexy
• Unruptured cerebral aneurysm or AVM
• Reversible cerebral vasoconstriction
• CSF hypovolemia syndrome
Treatment:
TACS
Treatment of Cluster
Headache: the challenge
A syndrome of:
-very severe, rapid onset, short duration
headaches(15-180min)
-with fast recovery (ie: resuming work)
-several attacks per 24 hours
-occurring at particular times and during sleep.
Treatment of Cluster
Headache: components
• 1. Rapid onset transitional treatment
• 2. Prophylactic treatment
• 3. Abortive treatment
1. Transitional Prophylaxis for
Rapid Suppression of Attacks
Options:
 Prednisone 60 mg po daily for 3 days, then decrease by 10
mg every 3 days (18days)
 Ergotamine tartrate 1-2 mg po/pr daily hs
 Greater occipital nerve blocks: lidocaine and Kenalog-40 or
6 mg betamethasone or 40 mg depomedrol
 DHE-45 0.5-1.0mg SC/IM q8-12h
------------------------------------------------------------------------- Methysergide 2 to 4 mg TID
 Decadron 4 mg BID for 2 weeks then 4mg Qday for 1 week
Greater Occipital Nerve Block
Lidocaine 1% or 2% with
betamethasone 6mg or
triamcinolone 40 mg
Uses:
-as transitional therapy instead
of prednisone
-to decrease frequency in
chronic cluster headache
-60% of patients have a
moderate to good response
after 1 injection.
Peres,M et al.,2002 Cephalalgia,22,520-22
2. Preventative Therapy
Throughout the anticipated duration of the cluster period: consider stopping
when 14 days headache-free)
• First Choice: Verapamil 80 mg TID (incr by 80mg
q10-14d); up to 720 mg/d. Check PR int. each dose
change. watch conduction block: ECG Q6m
• Methysergide maleate 2 mg TID; up to 12 mg/d
• Lithium Carbonate 150-300 mg tid
• Valproic acid 500-2000mg/day
• Topiramate 50-150/day
• Gabapentin 300 -3600 mg/day
• Melatonin 9-10 mg hs
Verapamil
240 to 960 mg/day
• Verapamil is the drug of choice for preventative therapy
• open labeled and controlled trials have demonstrated
effectiveness in 80% of cluster headache patients.
-In a RCT of 30 patients, 12 of 15 patients had a reduction in
frequency of attacks within two weeks.
• Side effects: heart block, constipation, dizziness, ankle
swelling, fatigue; rarely gum hypertrophy
Bussone G, Leone M, Peccarisi C, Micieli G, Granella F, Magri M, et al. Double blind comparison of lithium and verapamil in
cluster headache prophylaxis. Headache 1990;30:411-7.
Lithium

600 to 1200 mg per day
– (serum level: 0.4 to 0.8 mEq/L)

many trials with good results in 60 to 80%
of pts (esp. chronic cluster headache)
– In a double-blind crossover study of 30
patients, 50% of patients responded in 2 weeks

Potential for many side effects and has a
narrow therapeutic window.
Steiner TJ, Double-blind placebo-controlled trial of lithium in episodic cluster headache.
Cephalalgia 1997;17:673-5
Methysergide
•2 mg TID (max. 12 mg/day)
•decreased headache frequency by >50 percent in 19/20 patients
in a pilot study.
• use discontinued in the USA:
-can cause retroperitoneal, cardiac, and pleuropulmonary
fibrosis.
•Should be restricted to use in refractory cases and should never
be used for more than six months continuously; 1 month drug
holiday at that time along with regular screening tests.
Mueller L, Gallagher RM, Ciervo CA. Headache 1997;37:437-42.
Other drugs that can be tried for the estimated 30%
chronic cluster patients who fail usual treatment














Clonidine
Diltiazem
Flunarizine
Somatostatin
Indomethacin
Pizotifen
Phenelzine
Naratriptan
Gabapentin
Methylphenidate
Mirtazapine
Tizanidine
Baclofen
Warfarin
Management of Cluster
Headache: Abortive Therapy
OXYGEN INHALATION

Oxygen inhalation with a non-rebreathing facial mask at
least 7-12L/min for about 20 minutes in a sitting position

About 60 % patients respond with a substantial
reduction in pain in 20 to 30 minutes.
Mechanism of action unknown but may be related
cerebral vasoconstriction.

Cephalalgia 1991;11(Suppl.11):238-39
Nilsson et al., Cephalalgia 2002; 22: 730–39.
The Sumatriptan Cluster Headache Study Group.
Treatment of acute cluster headache with
sumatriptan. N Engl J Med 1991;325:322-6
•Randomized,
double-blind,
placebo-controlled,
study: efficacy of 6
mg sumatriptan s/c.
•Headache relief was
reported within 15
min in 74% of
attacks (cf. placebo
26%, p <0.001).
Triptans: alternatives to Imitrex
injection

In placebo controlled trials, Sumatriptan
nasal spray 20 mg was effective within 30
min. (Van Vliet et al.,Neurology 2003; 60: 630–33).

Zolmitriptan oral and nasal spray is
effective within 30 minutes. (Bahra et
al.,Neurology 2000; 54: 1832–39).
Ergotamines
Ergotamine tartrate PO or S/L has been used for
years although there are no recent controlled
trials.
 Effective as transitional therapy BID (for 2 to 3
weeks) or at bedtime to prevent nocturnal
attacks. Generally too slow to use at the onset
of an attack.
 DHE S/C,IM,orIV :effective abortive therapy
within 15 minutes

(Lance and Goadsby, 2005.Mecanisms and management of Headache,pg 217)
(Dodick et al.,2000 Cephalalgia:20,787-803)
Management of Cluster
Headache: Abortive Therapy
Summary: Most Effective Drugs
– Oxygen inhalation by facial mask at 7-14L/min
– Sumatriptan 6 mg S/C injection
– Dihydroergotamine 0.5-1.0 mg IV,S/C,IM
– Zolmitriptan 5 mg IN
Abortive drug treatment
•
•
•
•
•
•
•
•
•
•
•
•
Oxygen
Sumatriptan succinate subcutaneous (SQ) injection
Sumatriptan nasal spray
Zolmitriptan
Dihydroergotamine (DHE) intramuscular (IM), subcutaneous, or
intravenous (IV) injection
Dihydroergotamine mesylate intranasal spray
Ergotamine tartrate sublingual
Intranasal lidocaine
Topical intranasal cocaine
Capsaicin
Butorphanol
Olanzapine
Non-Drug Treatment
Patients should avoid the following:
•Afternoon naps or significant changes in their sleeping habits
•Alcohol, especially during the cluster period
•Prolonged exposure to chemical agents such as cleaning
solvents,gasoline, and oil-based paint
•Excessive bursts of anger or extreme emotion
•Prolonged physical exertion
•Extreme changes in altitude
Biondi D, Mendes P. Treatment of primary headache: cluster headache. In: Standards of care for headache
diagnosis and treatment. Chicago (IL): National Headache Foundation; 2004. p. 59-72.
Intractable Cluster Headache
• Surgical Interventions
– GON nerve stimulation
– Deep Brain Stimulation
– Ablative procedures
Management of other TACs…
Paroxysmal Hemicrania

Indomethacin 25 mg TID for 10 days then
increase to 50 mg TID for 10 days and consider
75 mg TID. Resolution of the headache usually
occurs in first 2 days of the effective dose.

“Indotest”: 50 to 100mg IM (Antonaci et
al.,1998) – complete pain relief occurred for 8
hours with 50 mg and 11 hours for 100mg.
Suggests that if there is no response the
diagnosis should be reconsidered.
Paroxysmal Hemicrania
Prophylactic treatment
– Indomethacin:
 Typical maintenance dose: 25-100mg Qday
 In CPH – attempt drug withdrawal Q6months
 Consider adjunctive stomach protection.
– Patients who can’t tolerate indomethacin -- no other
drug has been shown to be consistently effective.
 The following may be tried: other NSAIDs, celecoxib,
verapamil, flunarizine, acetazolamide, steroids.
Mathew, 2000; Shabbir &McAbee 1994; Coria et al, 1992;
Goadbsy and Lance 2005
Treatment of SUNCT
•SUNCT thought to be highly refractory to all treatment.
•Recently, lamotrigine 100-300 mg daily has been reported
to be highly efficacious in 7 patients
•Gabapentin and topiramate may be second-line agents.
•Lidocaine IV
•Ltd surgical options
D’Andrea G,et al., Neurology 1999;53:1609;
Leone M, et al Cephalalgia 2000;20:845–7. D’Andrea G et al. Neurology 2001;57:1723–5
.Graff-Radford SB..Cephalalgia 2000;20:515–17. Matharu M. S. Neurology (in press).
Treatment of HC

Indomethacin (50-300 mg)
– Other NSAIDs may be tried

Melatonin 6-12 mghs

Topiramate, Verapamil, GON stim have
been considered.
(Silberstein, Lipton, Goadsby. Headache in Clinical Practice, 2nd Edition 2002)
Treatment of Tension
Type Headache
• Acute: ASA, NSAIDs, tylenol < 2d/w
• Preventative: Amitriptyline, Tizanidine
• Non-pharmacological therapies: massage,
osteopathic, trigger point inj.,
psychophysiological therapies
Some aspects of Treatment of
Migraine and Variants
ACUTE THERAPY
Match agent to headache intensity and
to the patient’s co-morbidities
 Use meds properly and have
reasonable expectations
 Treat early, treat aggressively
 Avoid rebound
 Avoid opioids or barbiturates


How many days in the last 3 months were
you at least 50% disabled ?
– Patients who have > 10 days of disability in 3
months
(at work, home school or recreational activities):
should be offered triptans from the outset
Lipton et al., 2000 JAMA284: 2599-2605
Migraine Treatment Algorithm
Migraine severity assessment
First Line
Intermittent Mild to
Moderate
Intermittent
Moderate to Severe
On lack of efficacy
ASA/NSAID
(high dose)
ASA/acetaminophen
± anti-emetic
Oral triptan PRN
Oral triptan PRN
Nasal spray/
subcutaneous
triptan
Alternative oral
triptan
Nasal spray/
subcutaneous
triptan
Alternative oral
triptan
Frequent
Suspect chronic daily
headache
Consider Prophylaxis or
Refer to specialist
≥4 attacks/month
Evaluate headache
frequency
Consider Prophylaxis + acute
treatment
<4 attacks/month
Adapted from Dowson AJ et al. Curr Med Res Opin. 2002;18:414-39.
Treatment of Migraine
Phase I
Prodrome
Phase II
Aura
Phase III
Early Headache
Acute
Mild-moderate
Disability
None
Moderate-severe
Disability
None
Phase IV
Late Headache
Phase V
Postdrome
Rescue
OTCs, NSAIDs,
Non-narcotic
analgesics
Triptans
(for moderate)
None
Triptans
Analgesics
None
Dowson AJ et al. Curr Med Res Opin. 2002;18:414-39. Silberstein SD. Neurology. 2000;55:754-62.
Chronic Daily Headache
• Affects 4% of the population
– 3%/year migraineurs transform to chronic
daily headache
• causes severe functional impairment
– Family life and work productivity
Scher AI et al Headache 1998;38:497-506; Castillo J et al Headache 1999:38: 497-506
Types of primary CDH
• Short-duration types: (<4hours)
– Chronic cluster headache
– Chronic paroxysmal hemicrania
– Hypnic headache
• Long-duration types: (>4hours)
–
–
–
–
–
Hemicrania continua
Chronic tension type headache
Chronic Migraine
Medication Overuse Headache
New Daily persistent headache
Migraine Progression
Low frequency episodic migraine
<10/m
High frequency episodic migraine
10-14/m
Chronic migraine
>15/m
Some factors associated with
chronification:









Obesity
Head injury
Low socioeconomic status and education
Caffeine overuse
Poor sleep quality (snoring)
Stressful life events
Co-morbid pain
Medication overuse
Attack Frequency
Bigal et al.,Headache 2002;42:575-581, Scher et al.,Curr Pain HeadacheRep.2002;6:486-91
Scher AI et al.,Pain 2003;106:81-9
Clinical features of transformed
migraine
Daily or almost daily head pain
 Average headache >4h/d (if untreated)
 At least one of the following

– History of migraine
– Increasing frequency with decreasing
severity of migrainous features over at
least 3months
– Has occasional typical migraines

Other causes eliminated
Silberstein and Lipton Neurology 1996;47:871-5.
Medications Implicated
High Probability
-Opioids
-Ergotamine
-Butalbital
-Caffeine
-ASA/ibuprofen
-Triptans
Possibly
-Nasal decongestants
Unlikely
-DHE
-Neuroleptics
-Naproxen sodium
Use of barbiturates and opiates
predicts chronic migraine
Risk for the Development of Transformed
Migraine by Medication Use
Medication
Barbiturates
Opiates
Triptans
NSAIDs
Odds Ratio
2.06
1.98
1.250
*0.850
Bigal, Lipton:_ AMPP Headache. 2008;48:1157-1168
95% CI
1.3 - 3.1
1.4 - 2.2
.9 - 1.7
.63 -1.17

What is happening with migraine therapy
in Canada?
Prophylactic Pharmacotherapy
Percent of Migraine Patients
(N=606)
Prophylactic drug use before and after specialist referral
100
90
80
70
70.4%
(n=427)
60
Before referral
After referral
50
40
30
20
30.9%
(n=187)
10
0
Jelinski SE et al. Cephalalgia. 2005;26:578-88.
Medication Overuse
•
20.8% (125/606)determined to be medication over-users by neurologists after
referral
Medications
No. (%) of total
medication over-users
Acetaminophen/NSAIDs*
84 (67.2%)
Opiates*
53 (42.4%)
Triptans*
27 (21.6%)
Barbiturate*
10 (8.0%)
Ergotamine*
3 (2.4%)
Others
7 (5.6%)
Jelinski SE et al. Cephalalgia.
2005;26:578-88.
Study Conclusions

In the primary care setting:
– Triptans are being underutilized
– Prophylactic medications are being
underutilized
– Medication overuse is a significant problem
 Opiate overuse is of particular concern
Jelinski SE et al. Cephalalgia. 2005;26:578-88.
Elimination of overuse is a necessary requirement
of remission
• Medication overuse can make headaches refractory
to abortive and preventive medication.
• Discontinuation results in significant
improvement: response to meds and decr freq HA.
• With withdrawal many convert to episodic migraine.
Zeeberg et. Al., Neurology 2006;66:1894-98; Cephalalgia 26:1192-98. Mathew et al., Neurology
1990;30:634-8
Guidelines
• Limit abortive agents to no more than 2 days per
week
• Patients who feel compelled to use abortives
more often should contact their doctor.
Recommended substances (drugs of first choice) for the prophylaxis
Evidence
Substances
Daily dose
Level
Beta blockers
Metoprolol
Propranolol
50–200 mg
40–240 mg
A
A
Tricyclic antidepressants
Amitriptyline
Nortriptyline
10-50 mg
10-50 mg
A
C
Antiepileptic drugs
Valproic acid
Topiramate
500–1800 mg
25–100 mg
A
A
Calcium channel blockers
Flunarizine
5–10 mg
A
US headache consortium guidelines Neurology 2000,54:1253 and http://www.aan.com/professionals/, Silberstein Headache
Currents 2006, Tfelt-Hanson Cephalalgia 2006,261265-74. S. Eversa et al., EFNS guideline on the drug treatment of migraine.
European Journal of Neurology 2006, 13: 560–572
Drugs of second choice for prophylaxis (less effective or more side effects)
Substances
Daily dose (mg)
Level
Gabapentin
1200–1600 mg
Candesartan
16 mg
Lisinopril
20 mg
Bisoprolol,Nadolol,Atenolol,Timolol
B
C
C
A-B
Methysergide
Pizotifen
4–12 mg
1.5-6 mg
C
A
Fluoxetine
20-40 mg
B
Petasites (Butterbur)
Tanacetum (feverfew)
Riboflavin
Magnesium
2 X 75
3 X 6.25 mg
400 mg
24 mmol (400mg)
B
C
C
C
US headache consortium guidelines Neurology 2000,54:1253 and http://www.aan.com/professionals/, Silberstein Headache
Currents 2006, Tfelt-Hanson Cephalalgia 2006,261265-74. S. Eversa et al., EFNS guideline on the drug treatment of migraine.
European Journal of Neurology 2006, 13: 560–572
Prophylactic Medications and co-morbidity in Migraine
Co-morbid
disease
Topa
BB
TCA
Weight
issues
avoid
Sleep
poor
++
HTN
depression
care
++
avoid +
+
+
++
anxiety
Essential
tremor
FMS
Aura
+
Gabapentin
++
care Valproic, lamictal
+
++
+
avoid avoid
bipolar
epilepsy
SSRI Other AED
+
+
+(Lyrica)
Lamictal
Pathophysiology of Chronic Migraine
1. Central sensitization after repeated bouts
of migraine
2. Damage to CNS pain modulation system
3. CNS changes due to medication overuse
4. Abnormal focal neurological activity (CNS
pain generators)
5. Persistent activity in a peripheral pain
generator (cervical pathology)
Ramadan, Nabih M. 2007. Current Trends in Migraine Prophylaxis.
Headache: The Journal of Head and Face Pain 47 (s1), S52-S57
Figure 4. Correlation of frequency of migraine attacks per month vs allodynia
Mathew, N. T. et al. Neurology 2004;63:848-852
Iron deposition in the PAG in chronic migraine
Welch M. Headache 2001;41:629-637
Physiological changes in analgesic
overuse
• Serotonin levels decrease
• 5HT-2A receptors (potentiate nociceptive
neurotransmission) are up-regulated
• Opiate exposure increases response of afferents
when stimulated and enhance desc. Pain facilitation
(RVM)
• Increase central responsiveness via increased release
of CGRP
Park,JW et al Headache 2005;45:1229-35
Felice and Porreca Cephalalgia 2009,29,1277-84
Persistent activity in a peripheral pain
generator
• Convergence of cervical and trigeminal
inputs
– Cervical spine disease may become a generator
of pain
Bartsch T Current pain and headache reports 2003;7: 371-76
Bogduk N J of Man and Phys Therapeutics 1992;15:67-70
Located neurons in the TNC that received
convergent input from dura and facial skin.
Chemical stimulation of the dura caused an
incr sensitivity of the cutaneous receptive
field neurons to mechanical and thermal
stimulation.
Both the dural and cutaneous receptive
fields increased.
Burstein et al., J Neurophysiol 1998; 79: 964-982
Both the dural and
cutaneous receptive
fields increased:
-before field was
only periorbital then
expands to incl. max and
mand regions after
chemical stimulation
Burstein, R. et al. J Neurophysiol 79: 964-982 1998
Abnormal focal neuronal activity
(CNS pain generators)
• PET Activation in spontaneous migraine contralateral to the
headache
• The contralateral PAG modulates the trigeminovascular
system
Secondary chronic migraine
MRI demonstrating a left-sided cavernoma (a and b) with an associated
developmental venous anomaly (c) in the dorsal midbrain region adjacent to
the periaqueductal grey matter
P Goadsby. Cephalalgia 2002;22: 107-111
Pain Modulating System
cortical
PAG
Emotional factors
and stress
analgesics
RVM
on
TNC
off
C2
TREATMENT GOALS
• Reduce headache frequency
• Reduce headache impact on ADLs
An approach to the treatment of
patients with CDH
1. Formulate the diagnosis
– Eliminate secondary causes
– Establish the primary headache disorder
 Always consider medication overuse syndrome
– Establish other potentially contributory comorbidities.
Treatment of transformed migraine
2.
Educate the patient about:
 Migraine - expectations
 appropriate use of medication
 lifestyle factors which may be
contributory




Stress management
CBT
Diet/exercise
Sleep/wake regular meals
Treatment of transformed migraine
3.
Begin a program of treatment designed to break
the cycle of transformation and raise the threshold
for migraines.
– Begin prophylactic treatment
– Stop all overused meds
– Replace with long-acting NSAIDS
– Use transitional meds as needed
4. Schedule follow up
Lipton et al.,Neurology 2003;60:1064-1070
Katsarva et al., Neurology 2003;60: 682
Migraine in kids
AAN 2004 – Acetaminophen, ibuprofen,
sumatriptan nasal spray (>12yo).
 Sumatriptan, riza and zomi also effective
in adolescents
 Preventative: Consider nonpharmacological methods first.

– flunarizine, elavil, propranolol, cyproheptidine,
Topa, valproate (none are FDA)

Childhood per. Syn. - symptomatic
Pregnancy
Consider CSVT, CVA, Pit tumors, eclampsia
Avoid drugs–most improve in 2nd trimester
Tylenol, NSAIDs to week 28 (DA)
Metoclopramide (category B) Opioids (tylenol codeine or hydrocodone rescue)
(cat C), Stemetil carefully
 IV hydration, metoclopramide, Mg
 GON block






Triptan registry. NEVER USE ERGOTS
PREGNANCY
Avoid prophylactics – biofeedback better
 Propranolol, verapamil, Topa (cat C)


Lactation – can use sumatriptan
– Tylenol, advil, naproxen, codeine, ketorolac,
Metoprolol, propranolol, prednisone all
compatible with breastfeeding.
– LactMED: http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?LACT
Trigeminovascular Model of Migraine
Trigeminal
nerve
INHIBITION
5-HT1D
5-HT1F
INFLAMMATION
Trigeminal nerve fibers release
the neuropeptide CGRP, and
cause sterile inflammation of the
dura matter and vasodilation and
cerebral blood flow changes of
the cerebral arteries
CGRP
calcitonin gene
related peptide
NK
neurokinin A
SP
substance P
CGRP
NK
SP
triptans
VASODILATION
CONSTRICTION 5-HT1B
Blood vessel
Adapted from Goadsby (1997).
Mechanism of action of Triptans
• 5-HT1B receptors—blood vessels
◦ Constrict dilated intracranial arteries
Potential cardiovascular risk
• 5-HT1D receptors—peripheral trigeminal sensory nerves
◦ Inhibit perivascular neuropeptide release (CGRP, Sub P,
Neurokinin)
Break vasodilator cycle—promote normalization
• 5-HT1D and 5-HT1F receptors—central TNC
◦ Interrupt pain transmission within brain
Reduce nausea? (nuc Solitarius)
The distribution of 5-HT1B and 5-HT1D receptors in the ophthalmic branch of the
trigeminal Vth nerve, in the brainstem sensory trigeminal nucleus caudalis and in the
solitary tract nucleus where they could mediate an antinausea effects.
(Richard Hargreaves,Headache 2007;47 [Suppl 1]:S26-S43)
Triptans have limitations
 Contraindicated:
– coronary disease vascular risk factors.
Var. response rate, consistency and tolerability
 Are assoc. with medication overuse headache
 Expensive

Cardiovascular Safety of
Triptans

Incidence of serious cardiovascular events
is extremely low. Risk-benefit profile
favors use in the absence of vascular risk
factors.
– Triptan cardiovascular safety expert panel of the American
Headache society – consensus statement
Headache 44(5):414, 2004
PHARMICOKINETICS OF TRIPTANS
Suma
Imitrex
Almo
Axert
Ele
Relpax
Nara
Amerge
Riza
Maxalt
Zolmi
Zomig
T½
hours
2
3.5
5
6
2-3
3
T max
hours
2
2.5
1.5
2.5
1
1
%Oral
Bioavail.
14
70
50
70
45
40
Metab.
MAO
P450/
MAO
P450
RENAL/
P450
MAO
P450/
MAO
Log D
-1.3
+0.35
+0.5
-0.2
-0.7
-0.7
Relief of Migraine Pain
Rizatriptan 10 mg
Sumatriptan 100 mg
Sumatriptan 50 mg
Headache
relief at
2 hours*
Zolmitriptan 2.5 mg
Eletriptan 40 mg
(95% CI)
Almotriptan 12.5 mg
Naratriptan 2.5 mg
0
10
20
30
40
% Patients
50
60
70
80
(N=24,089)
Adapted from Ferrari MD et al. Lancet 2001;358:1668-1675.
*Comparison of recommended initial doses in SPC and standard comparator in the meta-analysis (sumatriptan 100 mg).
Systematic reviews of comparable trials
.
http://www.jr2.ox.ac.uk/bandolier/index.html accessed April 2007
What to do if there is Suboptimal
headache relief or recurrence
Treat while headache is still mild
 Combine triptan with NSAID (Naproxen)
 Switch to another triptan or formulation or
another type of acute therapy
 Add a prophylactic agent
 Ensure there is no underlying medication
overuse

(Smith, T et al.,Headache 2005;45:983-991. Foley,K et al.,Headache 2005;45:538-45)
Prospective trial: treatment while pain is milder increases the probability of
achieving 24 pain free status
Freitag,F et al.,Headache 2007;47:519-530
Smith T. et al., Headache 2005;45:983-991
Chance of migraine 2.5X
more
during days 1-3 of the cycle
Figure
217">
MacGregor, E. A. et al. Neurology 2006;67:2154-2158
MacGregor E.A. et al., Neurology 2004;63:351-53
Pooled rel. risks of stroke stratified by migraine type, oral contraceptive use, and age
No of studies
Relative risk (95% CI)
Migraine (any)
All studies 14
2.16 (1.89 to 2.48)
Etminan, M
Case-control studies 11
2.18 (1.86 to 2.56)
BMJ 2005;330:63
Cohort studies 3
2.10 (1.61 to 2.75)
Migraine with aura
Case-control studies 7
2.27 (1.61 to 3.19)
Migraine without aura
Case-control studies 6
1.83 (1.06 to 3.15)
Migraine among oral contraceptive users
Case-control studies 3
8.72 (5.05 to 15.05)
Migraine among men and women <45 years
Case-control studies 9
2.36 (1.92 to 2.90)
Migraine among women <45 years
Case-control studies 7
2.76 (2.17 to 3.52)
Management of Menstrual
Migraine
Usual Acute therapies: NSAIDS or
triptans
 Mini-prophylaxis starting a few days
before expected headache or 10 days
after ovulation and continuing up to
one week:

– Increase dose of usual prophylactic or…
Short-term MM prophylaxis
Mg
Naproxen
DHE-45 NS
Estradiol gel
Estradiol patch
Sumatriptan
Naratriptan
Zolmitriptan
360 mg/d
550 mg BID
NS q8h
1.5 mg Qday
100 mg
25 mg TID
1 mg BID
2.5 mg BID
* Refers to before expected headache
Day 15-menses
Day -7 to +6
Day -2* to +4
Day -2* to +5
same
day -2 to +3
Day -2 to +3
Day -2 to +4
Extended duration OCPs
Sulak Headache 2007;47:27-37
ER
US Headache Consortium
Vinson Ann Emerg Med 2002 39:3, 215-222
Recommendations for first line
therapy in ER

American: IV prochlorperazine and DHE
or Sumatriptan s/c

Canadian: Dopamine Antagonist., then
DHE IV or Sumatriptan s/c
Evidence regarding opioids
1. Meperidine - not significantly different than IV
chlorpromazine, IM Ketorolac, IV DHE, DHE
and Metoclopramide.
(Lane PL Ann Emerg Med 1989;18:360-65. Larkin Ann Emerg Med 1992;21:919-24. Belgrade Neurology 1989;39:59092. Scherl Headache 1995;35:256-59.)
2.
There is insufficient evidence to establish how
to select 1 therapy over another. However
almost universal agreement by experts that
opioids should be the last choice in most
cases.
(Matcher Neurology 2000)
DHE

Dose
– IV or IM DHE 0.5 to 1.0 mg
 Pretreat (or cocktail) IV metoclopramide 10 mg OR
IV Prochlorperazine (5 to 10 mg) OR
IM hydroxyzine 50 mg or IM promethazine 25 mg

Caution: vascular disease, triptan use in the
previous 24 h
Colman, I Annals of Emerg Med 2005 Parenteral DHE for acute migraine. A review of the
literature.
Dopamine antagonists

Dose:
– Prochlor 10 mg IV (repeat q30 minX2)
– Chlorprom 10 mg IV (repeat q30minX2)
– Pretreat: IV NS bolus. +/-Diphenhydramine
25-50mg IV

Caution:
– Hypotension, Akathisia (Benztropine 1mg IV),
sedation (shouldn’t drive home)
Slow HC et. Al. Headache 2005;45:358-71 – Neuroleptics in headache
Metoclopramide

Dose:
– 10 mg IV over 15 minutes

Evidence:
– Open labeled, placebo controlled*, comparator trials
(vs Sumatriptan** and opioids)
– Meta-analysis
 Supports it as monotherapy or polytherapy with a 2nd
agent***.
Tek Ann Emerg med 1990*. Freidman Neurology 2005**. Cicek Emerg j med 2004*** Colman BMJ
2006
NSAIDS
Ketorolac 30 to 60 mg IM
 Evidence:

– Open labeled: effective in acute migraine ER*
– Comparator trials – similar to meperidine and
chlorpromazine. Prochlorpromazine superior
to Ketorolac in kids.
*Davis Am J Emerg Med 1993. Davis Am J Emerg Med 1995. Duare Ann
Emerg Med 1992. Larkin Ann Emerg Med 1992. Brousseau Ann Emerg Med
2004.
Triptans

Dose:
– 6 mg S/C

Evidence
– Placebo controlled – superior to placebo on primary
and secondary endpoints*
– Comparator trials – Metoclopramide and
Diphenhydramine similar on pain relief at 2 and 24
hours**. Chlorpromazine and Metoclopramide similar
to IM sumatriptan and metoclopramide***
*Akpunonu BE Ann Emerg Med 1995 ** Freidman BW Neurology 2005 ***Kelley J Accid Emerg Med 1997
Other options
IV Valproic acid (500 to 1000 mg IV in 100 mg
NS infused over 5-20 minutes)
 IV aspirin
 IV Magnesium (1 gram of magnesium phosphate
in 10% NS IV over 15 minutes)
 IV Steroids (4-20 mg IV dexamethasone or 125
mg IV hydrocortisone)

INTERNATIONAL CLASSIFICATION
of
HEADACHE DISORDERS
2nd edition
(ICHD-II)
Headache
a clinical tour
for residents part 2:
Secondary headache disorders
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
2010
Lucy Vieira MD
©International Headache Society 2003/4