Transcript migraine

Headache
and
Facial Pain
國立陽明大學
醫學院醫學系
神經學科
台北榮總 神經醫學中心
王署君
偏頭痛盛行率

大台北地區調查 (1997-1998):
一年的盛行率 (one year prevalence)︰9.1%
女性約有
14.4%
男性約有
4.5%

亞洲國家
一年的盛行率 (one year prevalence)︰8.4-12.7%
女性約有
11.3-14.4%
男性約有
3.6-6.7%

歐美國家
一年的盛行率 (one year prevalence)︰10-12.1%
女性約有
11.2-25%
男性約有
4.0-7.5% 。
25
Prevalence (%)
20
15
男性
女性
10
5
0
1519
2529
3539
4549
5559
6569
Age
Sex- and age-specific prevalence of migraine (Taipei)
偏頭痛之求醫行為
 一年內有

54﹪求診過醫師。
10.4﹪一年內求診醫師超過十次以上。
偏頭痛之求醫行為
 求診醫師的順序
家庭醫師（29.3﹪）
內科（17.4﹪）
耳鼻喉科醫師（14.3﹪）
神經科醫師（12.2﹪）
婦產科醫師（4.9﹪）
眼科（4.6﹪）
4.3﹪的病人求救過急診
偏頭痛之求醫行為
 藥物來源
藥房
61﹪
醫師處方 23﹪


7.5﹪病人一個月大於十次以上
2.5﹪每天吃止痛藥。
正確的診斷
 國際頭痛學會頒訂頭痛分類診斷標準
第一版


1988 年出版
中文版洪祖培等翻譯，1993年
 第二版 ︰2004 年
（已在2003 年九月於羅馬出版）
International Headache Society

Primary vs. secondary headache
The International Classification of Headache
Disorders 2nd edition (ICHD-II), 2004
Part one: Primary headaches
1. Migraine
2. Tension-type headache
3. Cluster headache and other trigeminal autonomic cephalalgias
4. Other primary headache
Part two: The secondary headache
5. Headache attributed to head and /or neck trauma
6. Headache attributed to cranial or cervical vascular disorders
7. Headache attributed to non-vascular intracranial disorder
8. Headache attributed to a substance or its withdrawal
9. Headache associated with noncephalic infection
10. Headache attributed to disorder of homoeostasis
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
Part three: Cranial neuralgias, central and primary facial pain and other
headaches
13. Cranial neuralgias and central causes of facial pain
14. Other headache, cranial neuralgia, central or primary facial pain
國際頭痛學會偏頭痛分類
1.1無預兆的偏頭痛(migraine without aura)
 1.2有預兆的偏頭痛(migraine with aura)
 1.3可能為偏頭痛前驅或相關症狀之孩童週期
性症候群
 1.4視網膜偏頭痛(retinal migraine)
 1.5偏頭痛之併發症(complications of
migraine)
 1.6 可能偏頭痛(probable migraine)

國際頭痛學會偏頭痛分類
無預兆偏頭痛 (ICHD-II code 1.1)
(migraine without aura)- common migraine

有預兆偏頭痛 (ICHD-II code 1.2)
(migraine with aura)- classical migraine

10:1 to 3: 1
Headache profiles for migraine
“Migraine, the Sick-headache”
 Moderate to severe headache,
 Onset between 10-30 y/o, female predominant (3:1)
 Unilateral, pulsating, exacerbated during physical
activities, functions prohibited or inhibited, associated
with nausea, vomiting, photophobia, phonophobia,
 Duration 4 to 72 hours; frequency varied (most
1/month)
 Triggers: hypoglycemia, menstruation, red wine,
stress, poor sleep, 3C
 Phases: prodrome, aura, headache, postdrome
Phases of Migraine
Pre-Headache
Premonitory
symptoms
Headache
Post-Headache
Aura
Postdrome
Migraine phase slide
Mild
© 2000 Primary Care Network
Moderate
Severe
Rescue
Premonitory symptoms
前趨症狀
前趨症狀：疲倦、打呵欠、想吃東西
Aura (預兆)







visual symptoms (spots of light, scotoma, fortification
[scintillating scotoma], zig-zag), hemifield
aphasia,
sensory symptoms
motor weakness
EXPLAINED BY FOCAL NEUROLOGICAL DEFICIT
Reversible, lasting 5 to 60 minutes,
headache follows within 1 hour
(視覺)預兆
預兆
偏頭痛發作：沒食慾、噁心、怕光怕吵、怕異味、
情緒差、不想活動
頭痛結束：無精打采 或 精力充沛
Migraine without aura
(ICHD-II)

A. At least 5 attacks1 fulfilling criteria B–D

B. Headache attacks lasting 4–72 hours (untreated or unsuccessfully)


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)
D. During headache at least one of the following:
 1. nausea and/or vomiting
 2. photophobia and phonophobia

E. Not attributed to another disorder
無預兆偏頭痛




A、至少有 5次能符合B－D項的發作。
B、頭痛發作持續 4－72小時。
C、頭痛至少具下列二項特徵：
1. 單側
2. 搏動性
3. 程度中等或重度
4. 日常身體活動加劇頭痛或導致避免此類活動如走
路或爬樓梯﹚
D、當頭痛發作時至少有下列一情形：
1. 噁心或嘔吐
2. 畏光及怕吵
預兆偏頭痛
A 至少有二次能符合B-D項的發作。
B 至少有下列三項特徵中之一項:
1. 完全恢復的視覺症狀，包括正向（即閃爍光，光點，與線）與／或負
向（即視覺喪失）症狀．
2. 完全恢復的感覺症狀，包括正向（即針刺感）與／或負向（即麻木）
症狀．
3. 完全恢復的失語症症狀．
C 至少有下列三項特徵中之兩項:
1. 單側視覺與／或單側感覺症狀．
2. 至少一種預兆症狀  5分鐘以上逐漸產生，或是二種以上症狀相繼發生。
3. 每一預兆症狀持續  5分鐘且 60分鐘。
D .偏頭痛在預兆後60分鐘內發生。
Complications of migraine
(ICHD-II code 1.5)

1.5.2 Status migrainosus
 Headache lasts  72 hour whether treated or not
 Severe headache

1.5.4 Migrainous infarction
Migraine with aura and > 60 minutes
Neuroimage reveals ischemic infarction in the
relevant area
Chronic migraine (1.5.1)
Headache fulfilling migraine without aura on
 15 days/month for  3 months
 Medication overuse headache should be
excluded
 The most disabling type of chronic daily
headache ( 15 days/month for  3 months)

Migraine Transformation
Episodic
Migraine
Tension-Type
headache
Time
Mixed
Headache
Chronic Daily
Headache
Migraine Symptomatology
Hypersensitivity
 vessels pulsing normally can be felt to
throb;
 fluid in an otherwise satisfied stomach is
perceived as nausea;
 normal lights, sounds, or smells are
perceived as pungent or unpleasant;
 and normal movement is perceived to jar
and disturb the head.
Pathophysiology of Migraine

What causes migraine?
genetic component
a diathesis or constitution liable
to headache
Genetics of Migraine



70% positive family history (one parent:
46%, both parents: 66%)
stronger relationship with migraine with
aura
multiple genes vs. monogene
Genetic study of migraine

Familiar hemiplegic migraine (FHM)

CADASIL (cerebral autosomal dominant
arteriopahty with subcortical infracts and
leukoencephalopathy)
Familial
1.2.41.2.4
Familial
hemiplegic
migraine (FHM)
hemiplegic
migraine
(FHM)
A. At least 2 attacks fulfilling criteria B and C
B. Aura consisting of fully reversible motor weakness
and 1 of:
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
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Familial
1.2.41.2.4
Familial
hemiplegic
migraine (FHM)
hemiplegic
migraine
(FHM)
C. At least two of the following:
1. at least 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 min and <24 h
3. headache fulfilling criteria B-D for 1.1 Migraine
without aura begins during the aura or follows
onset of aura within 60 min
D. At least one 1st- or 2nd-degree relative fulfils these
criteria
E. Not attributed to another disorder
ICHD-II. Cephalalgia 2004; 24 (Suppl 1)
©International Headache Society 2003/4
Familial hemiplegic migraine



(FHM)
FHM 1: 19p13 missense mutations in CACNA1A,
which encodes the pore-forming 1 subunit of
voltage-gated neuronal Cav2·1 (P/Q-type) calcium
channels. (Ophoff et al. Cell 1996)
FHM 2: 1q23 missense mutations in ATP1A2, which
encodes the 2 subunit of the Na+/K+ pump (De
Fusco et al. Nat Genet 2003)
FHM 3: 2q24 missense mutation in SCN1A, which
encodes the neuronal voltage-gated sodium channel
Nav1·1 (Dichgans et al. Lancet 2005)
CADASIL

CADASIL (cerebral autosomal dominant
arteriopahty with subcortical infracts and
leukoencephalopathy):
recurrent subcortical ischemic events
dementia (90% before death)
migraine with aura (22%)
Depression
Chromosome 19, notch 3, point mutation
Pathophysiology of
Migraine

Numb Brain:

Pain sensitive: skin, subcutaneous tissue, muscle,
extracranial arteries, periosteum of the skull, venous
sinuses, dura, middle meningeal and superficial temporal
arteries, CN 2,3, 5, 9, 10, first three cervical nerves

Traditional view:
 tension-type headache: ”muscle theory”
 migraine:
“vascular theory”
Aura- mechanisms


spreading cortical depression of Leao
1-3 mm/min
cerebral blood flow reduction
 spreading oligemia
 posterior cortex (area 7 and area 19)
 reduction enlarged to whole hemisphere flow changes in
both with and without aura
 flow-headache relationship is complex
 Aura : initiator of migraine or parallel presentation?
margarita
Top, High-field magnetic resonance images of an "inflated" right cerebral hemisphere taken
across a course of 20 minutes, including 12 minutes after the onset of exercise-induced
migraine aura paracentrally in the left visual field (arrow)
Spierings, E. L. H. Arch Neurol 2004;61:794-799.
Copyright restrictions may apply.
Blood flow and visual aura
GB_15
30 minutes
6 hours
3 hours
24 hours
Blood flow through
migraine attacks
gb_18
Cortical spreading depression
CSD.avi
Headache
 Source
of Pain
carotid artery dilatation
sterile neurogenic inflammation (Moskowitz)
neurogenic plasma extravasation as an
index
 blocked by 5-HT 1B/D-like agonist (such
as sumatriptan),
Pulsation of temporal artery
decreases after ergotamine treatment
Neurogenic inflammation

動物實驗證實，腦血管周圍的神經炎症反應可由刺激感
覺神纖維造成。它們釋放substance P, CGRP 和
neurokinin-A使血管擴張和血漿外滲 (plasma
extravasation) 進而引起此反應。

此一反應可被sumatriptan和ergotamine抑制，這是
因為炎症反應與三叉神經血管系統纖維之前連結受器
(prejunctional receptor) 含有 5HT-1B/ID 受器有關。

除此之外，此前連結受器亦含有 2-adrenoceptor、
histamine H3受體、-opioid 和 somatostatin等受
體，故也可解釋為何其他藥物也 可用來治療急性偏頭
痛。
Neurogenic inflammation
GB_23
Classification of Serotonin
Receptors modern
5-HT 1A, 1B, 1D, 1F
 5-HT 2A, 2B, 2C
 5-HT 3
 5-HT 4
 5-HT 5A, 5B
 5-HT 6
 5-HT 7

Therapy and
Pathophysiology

5-HT 1B/D -like agonist
1B more cerebrovascular receptors
1D more trigeminal neuronal receptors

trigeminovascular system—
the common focus of activity for
vascular headaches
How to work out headache patients
why further study?






History: headache profile, painkillers,triggers…..
physical exam
lab
neuroimaging studies: CT scan or MRI, EEG ?
lumbar puncture
other specialty: ENT, dentist, psychiatrist
(associated with major depression, panic disorder,
and generalized anxiety disorder), rehabilitation for
neck problems
what patients should be kept an eye on?
(secondary headaches)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
first or worst headache
with fever
with confusion
post-traumatic
changing pattern
with convulsion
on awakening
nuchal rigidity
美國神經學會建議

“一個偏頭痛的病人，包含有視覺預兆之病人，若近期
頭痛情況沒有改變、沒有癲癇、沒有神經學症狀與徵
候，是不需做神經放射診斷。”

Frishberg BM 1994
 CT or MRI
 4/987(0.4%)
 ( 3/腫瘤, 1動靜脈畸形)

14/50(28%)病人懷疑自己是否長了腫瘤？
(Blau JN 1984)

30% 降低焦慮
急性發作處理
1.
大部分病患，只需要急性治療。
2. 頭痛、噁心、嘔吐。
急性發作處理
1. Triptans (翠普登
英明格 Sumatriptan（Imigran）
2. 抗多巴胺藥物：
抗精神藥物、止吐劑、助腸蠕動劑
3. 麥角胺鹼
4. 輕度止痛藥
(aspirin與acetaminophen or
combinations with or without caffeine)
5. NSAIDs
6. 類固醇
7. 麻醉劑
Simple analgesics
(輕微止痛藥）
 指Aspirin
和 Acetaminophen。
 藥效較弱，適合輕到中度發作。
 需其他藥物，如助腸蠕動劑共同使用。
 常與Caffeine 合用，多為成藥。
 價格便宜，且易造成濫用。
常見市售成藥止痛藥之成分
Pain-killers (OTC)
阿斯匹靈
腦新散(包)
(大陽)
速定二層錠
(中國化學)
227毫克
散利痛
(羅氏)
百服寧
(必治妥)
乙醯氨酚
Ethezamide
咖啡因
270毫克
100毫克
60毫克
125毫克
25毫克
Antacid
250毫克
50毫克
Isopropylantipyrine
(150毫克)
325毫克
Antacid
普拿疼
(加強錠)
500毫克
普拿疼
325毫克
齒痛五分珠
(包)
300毫克
五分珠(散)
520毫克
其他
65毫克
400毫克
260毫克
明通治痛丹
200毫克
斯斯解痛錠
500毫克
長安止痛錠
267毫克
80毫克
Bucetin (200毫克)
Bromvalerylurea (180毫克)
32.5毫克
350毫克
50毫克
Bromvalerylurea (200毫克)
30毫克
300毫克
83毫克
Bromvalerylurea (100毫克)
NSAIDS
1. 所有的NSAID都可治療急性發作。
2. IV (Ketorolac) 和 IM 比 PO 有效。
3. ibuprofen（400mg）
naproxen（500-1000mg）
4. 輕到中度發作。
5. 可用於預防月經性偏頭痛。
抗多巴胺藥物
（Anti-dopaminergic agents）




原作用是抗精神藥物、止吐劑或
助腸蠕動劑
控制噁心、嘔吐。
可加強藥物於腸胃道吸收。
metoclopromide（10 mg）（Primperan）
prochlorperazine（10 mg）（Novamin）
promethazine（12.5-25mg）（Pyrethia）
droperidol（2.5 mg）
Triptans (翠普登﹚
HT1B/ID-like 接受器催動劑。
 作用在抑制Trigeminovascular system活性。
 專門用來治療偏頭痛。
 最新且最有效藥物。
 且不需其他藥物共同使用。
 孕婦與冠狀動脈心臟病患者禁止使用。
 價格昂貴。
 副作用︰Triptan syndrome，
Cardiovascular side effects。
 5-
Triptans
台灣上市︰sumatriptan 50
健保給付︰sumatriptan 50 mg （每月八顆﹚
通過審核︰rizatriptan 10mg
naratriptan 2.5mg
sumatriptan nasal spray 20mg
zomitriptan 2.5 mg
完成臨床試驗︰eletriptan 40, 80 mg （未通過﹚。
Ergotamine
1. Cafergot （1mg：100 mg咖啡因）（加非葛﹚
先吃二片，一小時後再吃二片
（一天不超過六片，一星期不超過10片）。
2. 同時服用metoclopromide (10 mg) 兩顆。
止痛藥過度使用
(medication overuse)
（1）單純止痛藥（simple analgesics）：
＞ 15天/月，＞三個月
（2）複方止痛藥（combination analgesics）
（含咖啡因、巴比妥類藥物）：
＞ 10天/月，＞三個月
（3）麥角鹼（ergotamine）
＞ 10天/月，＞三個月
（4）麻醉劑（narcotics）：
＞ 10天/月，＞三個月
(5) 翠普登類
＞10天/月，＞三個月
預防發作處理
那些人需要預防？
(1)每週發作大於二次。
(2)發作時間長，超過 48小時。
(3)頭痛的程度非常嚴重。
(4)急性的處理往往無法完全減輕疼痛。
(5)頭痛前之預兆時間太長。
(6) 病人的意願與個人化也要顧及。

預防藥物
1. 80%病人至少減少50%發作次數。
2. β-阻斷劑、鈣離子阻斷劑、三環抗抑
鬱劑、抗癲癇藥物、血漿素抑制劑。
3. 需四至六星期，才會見效。
4. 超過 6 個月，發作情形已控制，可開始
減藥。
預防發作治療
1. β-阻斷劑（如：propranolol）。
2. 三環抗抑鬱劑（如：amitryptyline）。
3. 鈣離子阻斷劑
（如：flunarizine, verapamil）。
4. 抗癲癇藥物
（如：topiramate, valproic acid）。
5. 血漿素受器拮抗 (methysergide)。
Tension-type Headache (緊縮型頭痛)

Epidemiology (USA):
38% for one-year prevalence (female 42% and men,
36% )

Headache profile:
Episodic or chronic ( < or >= 15 days/month)
Most frequent headaches,
Mild to moderate,
Bilateral, non-pulsating (band-like),
functions mildly or not inhibited,
Duration varied 30 minutes to 7 days,
No marked accompanied symptoms
Tension-type headache
Treatment
Acetaminophen, aspirin,
 NSAIDs,
 biofeedback
 TCA could be used as preventive agents

Cluster Headache (叢發性頭痛)
men predominantly,
 increasing in females in the Western countries,
 very low prevalence 0.1-0.3% (USA),
 onset 20 to 40

Cluster Headache (叢發性頭痛)










very severe 'stabbing' pain over the retro-bulbar
region,
unilateral,
coming in clusters,
lasting 2-3 months,
each headache 30-90 (15-180) minutes,
autonomic symptoms (nasal congestion, rhinorrhea,
lacrimation, conjunctival injection, forehead and facial
sweating, miosis, ptosis, eyelid edema)
restlessness
1-8 times a day
attacks of frequently fixed time schedule
occurring most frequently during sleep
Mechanisms
Hypothalamus lesion?
Circadian rhythm dysfunction?
Autonomic mechanism of cluster headache
Hypothalamus
in cluster period
Treatment of cluster headache
 Abortive
agents:
oxygen inhalation
ergotamine
dihydroergotamine,
sumatriptan
 Preventive
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
agents:
steroids
verapamil
lithium
methysergide
valproic acid
台灣地區叢發性頭痛
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男女比例 6:1，與抽煙有關。
慢性叢發性頭痛患者非常少見。
好發月份是十一月到二月份。
北部地區多於南部地區
與氣候有關，特別是日照長短與變化。
單側發作，最常見自主神經症狀是流眼淚。
高比例病患有噁心、嘔吐、畏光、怕吵。
發作時有 50% 病患會 restlessness。
對類固醇與氧氣反應佳 (70-80%)。
預防用藥 verapamil (>240 mg/day) 效果佳。
Trigeminal Neuralgia (三叉神經痛)
Tics
 onset late in life (6th and 7th decades),
more in females
Pain Characteristics:

brief (seconds to less than 2 minutes)
unilateral (95-97%) paroxysms of electric-like and
lanciating pain, distributed V2-3 (<5% in V1)
maximum intensity lasting a second or slightly
longer and repetitively
‘triggers’: brushing teeth, chewing, talking, cold
wind to the face, etc.
Mechanism
focal demyelination of the trigeminal nerve
 vascular compression just prior to entry into
the pons (88%)
 6% tumor or aneurysm, 6% multiple sclerosis

Treatment

Medical:
carbamazepine, phenytoin, baclofen,
valproic acid, lamotrigine

Surgery:
Jenetta's operation: decompression of 5th
nerve
Gamma Knife
Thank you for
your attention!