Supporting File

Nyeri Kepala/ Headache

RED Flags Headache
MIGRAINE
TATALAKSANA MIGRAIN
N-VNS DEVICE
SCORING TOOLS
KARAKTERISTIK NYERI KEPALA
PAIN SENSITIVE AREAS OF HEAD AND NECK

1. cranium (periosteum)
2.muscles
3.nerves
4. vessels
5.subcutan tissue
6.eyes
7. ears
8. sinus
9. mucous
membrane

Intra Kranial
Arteri cerebri
Durameter di dasar otak
Pembuluh darah besar dan sinus venosus
Saraf kraniales V, IX, X
Saraf spinal servikal atas
Sinus venous dan cabang kortikalnya

Ekstra Kranial
Mata dan orbita, telinga, sinus paranasales,
Hidung, mastoid, orofaring, gigi, kulit kepala,
Kuduk dan vertebra servikal
Bangunan Peka Nyeri di Kepala

Struktur intrakranial
• Sinus kranialis dan vena aferen ( sinus venosus dan vena –
vena yang mensupply sinus )
• Arteri dari duramater ( arteri meningea media )
• Arteri basis crani yang membentuk sirkulus willisii dan
cabang – cabang besarnya
• Sebagian dari duramater yang berdekatan dengan
pembuluh darah besar terutama yang terletak di basis
fossa kranii anterior dan posterior

(Sjahrir, 2008)
 Bangunan Peka Nyeri di Kepala

Struktur ekstrakranial
• Kulit, otot, tendon dan fascia daerah kepala dan leher
• Mukosa sinus paranasal dan cavum nasi
• Gigi geligi
• Telinga luar dan tengah
• Tulang tengkorak terutama daerah supra orbita, temporal,
dan oksipital bawah, rongga orbita beserta isinya.
• Arteri ekstrakranial

(Sjahrir, 2008)
Bangunan Peka Nyeri di Kepala
Saraf
• Nervus trigeminus, fasialis,
glossofaringeus, dan vagus
• Saraf spinal servikalis 1, 2, 3.

(Sjahrir, 2008)
Penyebab NK

1. Traksi atau pergeseran sinus venosus dan

cabang kortikalnya,
2. Traksi, dilatasi atau inflamasi yang melibatkan
arteri intra dan ekstrakranial
3. Traksi, pergeseran atau penyakit n. kranialis
V, VII, IX, X serta n. servikal 1,2,3
4. Perubahan tekanan intrakranial
5. Penyakit jaringan kulit kepala, wajah, mata,
hidung, telinga, dan atau leher

(Sjahrir, 2008)
 International Classification of Headache

• Nyeri kepala primer

• Migren
• Tension type headache
• Nyer kepala klaster dan sefalgia trigeminal-otonomik lainnya
• Nyeri kepala primer lainnya
• Nyeri kepala sekunder
• Nyeri kepala yang berkaitan dengan trauma kepala dan/atau leher
• Nyeri kepala yang berkaitan dengan kelainan vaskuler cranial dan/atau servikalis
• Nyeri kepala yang berkaitan denngan kelainan non vaskuler
• Nyeri kepala yang berkaitan dengan suatu substansi atau proses withdrawalnya
• Nyeri kepala yang berkaitan dengan infeksi
• Nyeri kepala yang berkaitan dengan kelainan hemostasis
• Nyeri kepala yang berkaitan dengan kelainan cranium, leher, mata, telinga, hidung, sinus, gigi,
mulut atau struktur facial atau cranial lainnya.
• Nyeri kepala yang berkaitan dengan kelainan psikiatrik
MIGRAINE HEADACHE
Anamnesis
 Migrain dengan Aura
Minimal 2 karakteristik
berikut :

Aura menyebar Masing- Setidaknya Aura disertai

bertahap ≥5 masing satu gejala dengan atau
menit, dan/atau gejala aura aura diikuti nyeri
dua atau lebih berlangsung unilateral kepala dalam
gejala aura yang antara 5-60 waktu 60
terjadi menit menit
berurutan
Pemeriksaan Fisik
 AURA MIGRAINE HEADACHE
AURA
The aura is the complex of neurological
symptoms that
occurs usually before the headache.
Visual aura is the most common type of aura
(90%). It often presents as: a zigzag figure near
the point of fixation that may gradually spread
right or left.
Sensory aura, in the form of pins and needles
moving slowly from the point of origin to one
side of the body, speech aura, usually aphasic
but often hard to categorize.
aura visual, sensory, and speech are Migraine
with typical aura in which aura is accompanied
or followed within 60 minutes by headache
with or without migraine characteristics.
Brainstem aura:
Description: Migraine with aura
symptoms clearly originating from the
brainstem, but no motor weakness.
at least two of the following fully
reversible brainstem symptoms:
a.dysarthria
b.vertigo
c.tinnitus
d.hypacusis
e.diplopia
f.ataxia not attributable to sensory
deficit
g.decreased level of consciousness
(GCS<13)
Retinal migraine
Description: Repeated attacks of
monocular visual disturbance,
including scintillations, scotomata or
blindness, associated with migraine
headache.
Jenis Aura
 AURA MIGRAINE HEADACHE
Motor Aura:
Aura consisting of both of the following:
1.fully reversible motor weakness
2.fully reversible visual, sensory and/or
speech/
language symptoms.
Motor symptoms generally last less than 72
hours
Familial hemiplegic migraine (FHM)
Description: Migraine with aura including
motor weakness, and at least one first- or
second-degree relative has migraine aura
including motor weakness.
Sporadic hemiplegic migraine (SHM)
Description: Migraine with aura including
motor weakness, and no first- or second-
degree relative has migraine aura including
motor weakness
1.3 Chronic Migraine
Diagnostic criteria:
A.Headache (migraine-like or tension-
type-like) on 15 days/month for >3
months, and fulfilling criteria B and C
B.Occurring in a patient who has had at
least five attacks fulfilling criteria B–D for
Migraine without aura and/or criteria B
and C for Migraine
with aura
C.On 8 days/month for >3 months,
fulfilling any
of the following:
1.criteria C and D for 1.1 Migraine
without aura
2.criteria B and C for 1.2 Migraine with
aura
3.believed by the patient to be migraine
at onset
and relieved by a triptan or ergot
derivative
MIGRAINE PHASES

Fase Fase Nyeri Fase

Fase Aura
Prodormal Kepala Postdormal
(5-60 menit) (24-48 jam)
(jam-hari) (4-72 jam)
 MIGRAINE TRIGGERS

Hormonal
Menstruation, ovulation, oral contraceptive agents, hormonal replacement therapy

Dietary
nitrite-laden meat, monosodium glutamate, aspartame, chocolate, aged cheese,
missing a meal Beverages Caffeinated beverages, beers, wines

Psychological
Stress, post-stress (weekends or vacation), anxiety,
worry, depression

Environmental
Glare, flashing lights, visual stimulation, fluorescent lighting, odors , weather changes,
high altitude

Sleep-related
Lack of sleep, excessive sleep

Drugs
Nitroglycerin, histamine, reserpine, hydralazine, ranitidine, estrogen

Miscellaneous
Head trauma, physical exertion, fatigue
 MIGRAINE PATHOPHYSIOLOGY
Teori Vaskular

Aura pada migrain diperkirakan akibat vasokonstriksi pembuluh darah intracranial

yang menginduksi iskemi jaringan. Selanjutnya terjadi rebound vasodilatasi dengan
mengaktifkan saraf nosiseptif perivascular yang akhirnya menyebabkan nyeri kepala.

Teori Neurovaskular

Migrain pada awalnya merupakan proses neurogenic yang kemudian diikuti dengan
perubahan perfusi serebral (neuro ke vascular)

At baseline, a migraineur who is not having any headache has a state of neuronal
hyperexcitability in the cerebral cortex, especially in the occipital cortex. This
finding has been demonstrated in studies of transcranial magnetic stimulation and
with functional magnetic resonance imaging
 MIGRAINE PATHOPHYSIOLOGY

Cortical spreading depression

the theory of cortical spreading depression (CSD) to explain the mechanism of migraine with aura.
CSD is a well-defined wave of neuronal excitation in the cortical gray matter that spreads from its
site of origin at the rate of 2-6 mm/min.

This cellular depolarization causes the primary cortical phenomenon or aura phase; in turn, it activates
trigeminal fibers, causing the headache phase. The neurochemical basis of the CSD is the release of
potassium or the excitatory amino acid glutamate from neural tissue. This release depolarizes the
adjacent tissue, which, in turn, releases more neurotransmitters, propagating the spreading depression.

Trigeminovascular system
Activation of the trigeminovascular system by CSD stimulates nociceptive neurons on dural blood
vessels to release plasma proteins and pain-generating substances such as calcitonin gene-related
peptide, substance P, vasoactive intestinal peptide, and neurokinin A. The resultant state of sterile
inflammation is accompanied by further vasodilation, producing pain.

The initial cortical hyperperfusion in CSD is partly mediated by the release of trigeminal and
parasympathetic neurotransmitters from perivascular nerve fibers, whereas delayed meningeal blood
flow increase is mediated by a trigeminal-parasympathetic brainstem connection. According to Moulton
et al, altered descending modulation in the brainstem has been postulated to contribute to the
headache phase of migraine; this leads to loss of inhibition or enhanced facilitation, resulting in
trigeminovascular neuron hyperexcitability.
MIGRAINE PATOPHYSIOLOGY
Migraine center

A potential "migraine center" in the brainstem has been proposed, based on PET-scan
results showing persistently elevated rCBF in the brainstem (ie, periaqueductal gray,
midbrain reticular formation, locus ceruleus) even after sumatriptan- produced
resolution of headache and related symptoms.

Brainstem activation
PET scanning in patients having an acute migraine headache demonstrates activation of
the contralateral pons, even after medications abort the pain. Weiler et al proposed
that brainstem activation may be the initiating factor of migraine.

Once the CSD occurs on the surface of the brain, H+ and K+ ions diffuse to the pia mater
and activate C-fiber meningeal nociceptors, releasing a proinflammatory soup of
neurochemicals (eg, calcitonin gene–related peptide) and causing plasma extravasation
to occur. Therefore, a sterile, neurogenic inflammation of the trigeminovascular complex
is present.

Once the trigeminal system is activated, it stimulates the cranial vessels to dilate.
The final common pathway to the throbbing headache is the dilatation of blood
vessels.
 Five step treatment ‘ladder’
in Acute Migraine
• Step 1: Oral Analgesics ± Antiemetic
• Step 2: Parenteral/Rectal Analgesic ± Antiemetic
• Step 3: Triptans or Ergotamine (Specific)
• Step 4: Combinations (Steps 1+3, followed by Steps 2+3)
• Step 5: Emergency treatment

British Association for the Study of Headache, 2010,

Guidelines for All Healthcare Professionals in the Diagnosis and Management of Migraine
TERAPI MIGRAIN

PREVENTIVE TREATMENT For:

patients have frequent attacks:
• > 2-3 attacks/month & each attack >48 hrs
• Abortive treatment is inadequate or produces intolerable adverse effects
• Uncommon headache
condition

trial (2 - 6 months)
Periodic, slow taper
 MIGRAINE THERAPY

successful abortive tx:

• pain-free status in 2hrs post tx

• pain-free status lasts atleast 24hrs
post tx
• better intensity (mod to mild or
severe to mod)
Mechanism of action of NSAID

ARACHIDONIC ACID

COX-1 KETOROLAC COX-2

PROSTAGLANDINS / PROSTAGLANDINS
TROMBOXANE

Primarily Primarily protect Primarily mediated

support platelet gastroduodenal mucosa inflammation,
function pain, fever
Parasetamol bekerja secara non selektif
dengan menghambat enzim siklooksigenase
(cox-1 dan cox-2). Pada cox-1 memiliki efek
cytoprotektif yaitu
melindungi mukosa lambung, apabila
dihambat akan terjadi efek samping pada
gastrointestinal. Sedangkan ketika cox-2
dihambat akan menyebabkan menurunnya
produksi prostaglandin. Prostaglandin
merupakan mediator nyeri, demam dan anti
inflamasi. Sehingga apabila parasetamol
menghambat prostaglandin menyebabkan
menurunnya rasa nyeri.

Sebagai Antipiretik, parasetamol bekerja

dengan
menghambat cox-3 pada hipotalamus.
Parasetamol memiliki sifat yang lipofil
sehingga mampu menembus Blood Brain
Barrier, sehingga menjadi first line pada
antipiretik
Caffeine for Migraines
 WHY THE NEED FOR PROPHYLAXIS ?

Abortive drugs should not be used more than 2-3

times a week
Long-term prophylaxis improves quality of life by
reducing frequency and severity of attacks
80% of migraineurs may require prophylaxis
Mechanism of action of PROPANOLOL
Mechanisms proposed
• Vasoconstriction
• Anxiolytic action
• Decreased sympathetic activity
Starting dose: 40-80 mg once daily
Max. dose/day: 240 mg
Taper slowly to avoid rebound headache and adrenergic side
effects
Max. duration: 9 to 12 months
Terapi Non Farmakologis Migrain
NON PHARMACOLOGIC TREATMENTS
RELAXATION TRAINING BIOFEEDBACK

A technique where the person receives extra feedback about

this includes: progressive Muscle Relaxation (PMR) and the state that their body is in.
meditation or passiev relaxation
It’s then the person’s job to use the feedback they get to
terhadap pasien, berupa : make changes in their own body
• Mengidentifikasi penyebab stress yg berperan sbg
pencetus nyeri kepala→strategi pengelolaan stress Mengajarkan kepada pasien untuk mengontrol fungsi tubuh,
seperti HR, TD, muscle tension  secara voluntir
Kursus biofeed back 8-10 sesi @30-45 mnt
CBT includes:
- Conditioning
the mixture between cognitive therapy and behavioral - Feed back
therapy.e point: how the patients think about certain - Intrumentasi
situation affecting how they feel emotionally& - Behavior modification
physically, and changing their behaviour - Adaptation
the key of CBT: to identify the most important thought,
emotion, and behaviour to decide the best reaction
Normal Sleep Pattern

• Siklus tidur antara NREM dan REM

+90min
• Durasi dan frekuensi REM meningkat
bila semakin malam
• Proportion of slow wave sleep
(stages 3,4) menurun bila semakin
malam
Teknik Neuromodulasi
 n-VNS

(non invasine vagus nerve stimulation)

 Now, new
device has
been
developed
.
neuromodulation therapy

noninvasive vagus
nerve stimulation Future
guidelines
(nVNS)
currently
under
nVNS of the cervical branch at
developmen
the neck (GammaCore®, NJ,
t
USA)

The cervical nVNS device produces a low-voltage electrical signal (5-kHz sine wave
series that occurs for 1 ms and is repeated every 40 ms [25 Hz]) that delivers a
maximum output current of 24 V and 60 mA. Two stainless steel contact surfaces
coated with a conductive gel enable delivery of stimulation to the neck in the vicinity
of the vagus nerve.
n-VNS
(non invasine vagus nerve stimulation)
The control group
(sham-device
treatment/ standard
care
The sham device was
identical in appearance,
weight, and visual and
audible feedback, and
produced a low-frequency
(0.1 Hz) biphasic signal
without actual stimulation.
Treatment group
Non-invasive vagus
nerve stimulation
(nVNS)
The cervical nVNS device
produces a low-voltage
electrical signal (5-kHz sine
wave series that occurs for
1 ms and is repeated every
40 ms [25 Hz]) that
delivers a maximum
output current of 24 V and
60 mA. Two stainless steel
contact surfaces coated
with a conductive gel
enable delivery of
stimulation to the neck in
the vicinity of the vagus
nerve.
In the acute nVNS treatment group,
each treatment consisted of two to
three 2-min self-administered
stimulations at the onset of
symptoms or pain, and optional
stimulation was allowed if needed
for 15 or 120 min.
In the preventive nVNS treatment
group, six 2-min stimulations a day
were administered within 1 h of
waking and 6~10 h after the first
treatment.
The therapy duration ranged 2~12
weeks.
CERVICAL n-VNS Migraine

PREVENTIVE TREATMENT

ACUTE TREATMENT
CERVICAL n-VNS Cluster Headache

PREVENTIVE TREATMENT

ACUTE TREATMENT
n-VNS
n-VNS
There is a great need in non-pharmacological treatment
of severe headaches – and neuromodulation may indeed
be an answer to this need.
Compared to the conventional neuromodulation
approaches (DBS, SCS, PNS, etc.) that use implantable
devices, non-invasive neuromodulation appeals to the
general public due to its lower risks and perceived
convenience.

SIDE EFFECTS

The most common side effects include discomfort and

redness at the application site as well as dizziness. A
tingling feeling where the device is applied is normal, but
it should not cause major discomfort.
MIGRAINE PROGNOSIS
Migraine is a chronic condition, but prolonged remissions
are common.
The severity and frequency of migraine attacks tend to
diminish with increasing age. After 15 years of suffering
migraines, approximately 30% of men and 40% of women
no longer have migraine attacks
 COMPLICATIONS MIGRAINE HEADACHE

• status migrainous: Description: A debilitating migraine attack lasting

for more than 72 hours.
• Persistent aura without infarction Aura symptoms persisting for one
week or more without evidence of infarction on neuroimaging.
• Migrainous infarction One or more migraine aura symptoms
occurring in association with an ischaemic brain.
• Migraine aura-triggered seizure : A seizure triggered by an attack of
migraine with aura.
TENSION TYPE
HEADACHE
2.1 Infrequent episodic tension-type headache
Diagnostic criteria:
A. At least 10 episodes of headache occurring on
<1 day/month on average (<12 days/year) and fulfilling
criteria B–D
B. Lasting from 30 minutes to seven days
C.At least two of the following four
characteristics:
1. bilateral location
2. pressing or tightening (non-pulsating) quality
3. mild or moderate intensity
4. not aggravated by routine physical activity
D. Both of the following:
1. no nausea or vomiting
2.no more than one of photophobia or
phonophobia
2.2 Frequent episodic tension-type headache
Diagnostic criteria:
A.At least 10 episodes of headache occurring on 1– 14
days/month on average for >3 months (12 and
<180 days/year) and fulfilling criteria B–D
B. Lasting from 30 minutes to seven days
C. At least two of the following four characteristics:
1. bilateral location
2. pressing or tightening (non-pulsating) quality
3. mild or moderate intensity
4.not aggravated by routine physical activity such as
walking or climbing stairs
D. Both of the following:
1. no nausea or vomiting
2.no more than one ofphotophobia or phonophobia
2.3 Chronic tension-type headache

Diagnostic criteria:
A. Headache occurring on 15 days/month on average
for >3 months (180 days/year), fulfilling criteria B–D
B. Lasting hours to days, or unremitting
C. At least two of the following four characteristics:
1. bilateral location
2. pressing or tightening (non-pulsating) quality
3. mild or moderate intensity
4. not aggravated by routine physical activity

D. Both of the following:

1. no more than one of photophobia, phonophobia or
mild nausea
2. neither moderate or severe nausea nor vomiting

1. Chronic tension-type headache associated with

pericranial tenderness

2.Chronic tension-type headache not associated with

pericranial tenderness
THERAPY TENSION TYPE HEADACHE
PROPHYLACTIC THERAPY:

• if the headache is frequent;

• no response with symptomatic tx
• dealing with QoL (work/ school),
• the usage of over-the-counter-analgesic increases
(>15days/month)
• effective: frequency and intensity is reduced by
50%

NON-PHARMACOLOGIC THERAPY:

• diet control
• physical therapy (relaxation/ massage)
CHRONIC TYPE TTH: • avoid triggering factors
1.antidepressan tricyclic: amitriptyline (by reducing firing rate of • behaviour therapy (counseling, stress
trigeminal nucleus caudatus management therapy)
2. anti anxiety: benzodiazepine (addictive)
CLUSTER HEADACHE
 The TACs share the clinical features of unilateral
headache and, usually, prominent cranial
parasympathetic autonomic features, which are
lateralized and ipsilateral to the headache.
3.1 Cluster headache
Diagnostic criteria:
A.At least five attacks fulfilling criteria B–D
B.Severe or very severe unilateral orbital,
supraorbital and/or temporal pain lasting 15–180
minutes
C.Either or both of the following:
1.at least one of , ipsilateral to the headache:
a)conjunctival injection and/or lacrimation
b)nasal congestion and/or rhinorrhoea
c)eyelid oedema
d)forehead and facial sweating
e)miosis and/or ptosis
2. a sense of restlessness or agitation
D. Occurring with a frequency between one every
other day and eight per day
1. Episodic cluster headache
Cluster headache attacks occurring in periods lasting from
seven days to one year, separated by pain-free periods
lasting at least three months.
2. Chronic cluster headache
CH occurring for one year or longer with remission
periods lasting less than three months.
3.2 Paroxysmal hemicrania
A.At least 20 attacks fulfilling criteria B–E
B.Severe unilateral orbital, supraorbital and/or
temporal pain lasting 2–30 minutes
C.Either or both of the following:
1.at least one of signs, ipsilateral to the
headache:
a)conjunctival injection and/or lacrimation
b)nasal congestion and/or rhinorrhoea
c)eyelid oedema
d)forehead and facial sweating
e)miosis and/or ptosis
2. a sense of restlessness or agitation
D. Occurring with a frequency of >5 per day1
E. Prevented absolutely by therapeutic doses of
indomethacin
 3.3 Short-lasting unilateral
neuralgiform headache attacks
Diagnostic criteria:
A.At least 20 attacks fulfilling criteria B–D
B.Moderate or severe unilateral head pain, with
orbital, supraorbital, temporal and/or other trigeminal B.Both of the following, ipsilateral to the
distribution, lasting for 1–600 seconds
and occurring as single stabs, series of stabs or in a saw- 1.conjunctival injection
tooth pattern
C.At least one of the following five cranial autonomic
symptoms or signs, ipsilateral to the pain:
1.conjunctival injection and/or lacrimation
2.nasal congestion and/or rhinorrhoea
3.eyelid oedema
4.forehead and facial sweating
5.miosis and/or ptosis
D. Occurring with a frequency of at least one a day
3.3.1 Short-lasting unilateral neuralgiform
headache attacks with conjunctival
injection and tearing (SUNCT) Diagnostic
criteria:
A.Attacks fulfilling criteria for 3.3 Short-
lasting unilateral neuralgiform headache
attacks, and criterion B below
pain:
2.lacrimation (tearing).
3.3.2 Short-lasting unilateral neuralgiform
headache attacks with cranial autonomic
symptoms (SUNA)
A.Attacks fulfilling criteria for 3.3 Short-
lasting unilateral neuralgiform headache
attacks, and criterion B below
B.Not more than one of the following,
ipsilateral to the pain:
1.conjunctival injection
2.lacrimation (tearing)
3.4 Hemicrania continua

Diagnostic criteria:
A. Unilateral headache fulfilling criteria B–D
B.Present for >3 months, with exacerbations of
moderate or greater intensity
C. Either or both of the following:
1. at least one of the following symptoms or
signs, ipsilateral to the headache:
a) conjunctival injection and/or lacrimation
b) nasal congestion and/or rhinorrhoea
c) eyelid oedema
d) forehead and facial sweating
e) miosis and/or ptosis
2. a sense of restlessness or agitation, or
aggravation of
the pain by movement
D. Responds absolutely to therapeutic doses
of
indomethacin
CLUSTER HEADACHE PATHOPHYSIOLOGY
Cluster headache (CH), also known as histamine headache,
is a primary neurovascular headache disorder.
The periodicity of the attacks suggests the involvement of a
biologic clock within the hypothalamus (which controls
circadian rhythms), with central disinhibition of the
nociceptive and autonomic pathways—specifically, the
trigeminal nociceptive pathways.
the posterior hypothalamic gray matter as the key area for
the basic defect in CH.
Functional hypothalamic dysfunction has been confirmed
by abnormal metabolism based on the N-acetylaspartate
neuronal marker in magnetic resonance spectroscopy.
Substance P neurons carry sensory and motor impulses in
the maxillary and ophthalmic divisions of the trigeminal
nerve. These connect with the sphenopalatine ganglion and
interior carotid perivascular sympathetic plexus.
Somatostatin inhibits substance P and reduces the duration
and intensity of CH.
CLUSTER HEADACHE PATHOPHYSIOLOGY

TRIGGERS to provoke CH
attacks:
Subcutaneous injection
of histamine provokes
attacks in 69% of
patients. Stress,
allergens, seasonal
changes, or nitroglycerin
may trigger attacks in
some patients. Alcohol
induces attacks during a
cluster but not during
remission. About 80% of
CH patients are heavy
smokers, and 50% have a
history of heavy ethanol
use.
CLUSTER HEADACHE THERAPY
Pharmacologic management of cluster headache
(CH) may be classified into 2 general approaches as
follows:
• Abortive/symptomatic (eg, oxygen, triptans,
ergot alkaloids, and anesthetics)
Inj.Sumatriptan SC 6mg
oksigen NRP 12lpm 15 menit

• Preventive/prophylactic (eg, calcium channel

blockers, mood stabilizers, and anticonvulsants)
verapamil 3x120mg
Steroid Prednison 60mg/day for min 5 days,
tapoff 10mg/day
valproic acid
gabapentin
CRITERIA FOR
PREVENTIVE TX:
• not effective
by abortive tx
•CH happens everyday more than 15 mins
Preventive treatment in episodic CH should be
given ASAP and given everyday during the attacks,
while in chronic type, this should be given
everyday
CLUSTER HEADACHE NON-PHARMACOLOGIC THERAPY
Nerve Blocks, Ablative Procedures, and Brain Stimulation

Various invasive nerve blocks and ablative neurosurgical procedures (eg, percutaneous radiofrequency/RF ablation,
trigeminal gangliorhizolysis, and rhizotomy) have been implemented successfully in cases of refractory CH.

Percutaneous RF ablation may achieve success in 50% of patients, with fair-to-good results in 20% and failure in
about 30%. Gamma-knife radiosurgery is a less invasive alternative for pervasive CH but is associated with a
significantly increased risk for facial sensory disturbances. Greater occipital nerve block may be beneficial in aborting
CH.

Deep brain stimulation with implantation of stimulating electrodes under stereotactic guidance into the ipsilateral
posterior inferior hypothalamus is another potential option for chronic CH refractory to pharmacologic therapy.
RISK: invasive, intracranial hemorrhage, subcutaneous infection, micturition syncope, and transient loss of
consciousness.

In 2017, the FDA approved a hand-held device to treat cluster headaches. The non-invasive device works by
transmitting mild electrical stimulation to the vagus nerve through the skin on the neck. Approval was based on 2
clinical trials (ACT1 and ACT2) showing that the device was more effective than placebo in reducing cluster headache
pain.
CLUSTER HEADACHE PROGNOSIS

Generally, CH is a lifelong problem. Potential outcomes include the following:

• Recurrent attacks

• Prolonged remissions

• Possibility of transformation of an episodic cluster to a chronic cluster and vice versa

BACKGROUN
D
TTH

Primary Headache Migrain neuromodulation

therapy
e therapy The control
group group
(14.7%) Non- (sham-device
cluster headache
invasive treatment/
(0.1%~0.4%) vagus nerve standard care
stimulation
other type of Primary (nVNS)
The therapy duration ranged 2~12 weeks.
headche
VAGUS NERVE
• The vagus nerve is the major parasympathetic branch of the autonomic
nervous system, whose primary functions include regulation of breathing,
heart rate, and digestion. The vagus nerve is a mixed nerve composed of 20%
“efferent” fibers and 80% “afferent” fibers.
• An important function of the vagus nerve is transmitting and/or mediating
sensory information from throughout the body to the brain.
• Nociceptive transmission is probably modulated through the activation of
vagus nerve afferents that go to the nucleus tractus solitarius, the area
postrema and spinal trigeminal nucleus in the brainstem and spread to
higher structures including the locus coeruleus, the periaqueductal grey, the
raphe magnus, the thalamus and hypothalamus.
•
The mechanism of action of nVNS in the treatment of headache is largely
elusive and likely multifactorial. In animal models, iVNS is able to modulate the
firing of trigeminal nucleus caudalis neurons in response to dura mater
stimulation
X: Vagus nerve
Rootlets of the vagus nerve attach to the lateral aspect of
the medulla immediately caudal to the
glossopharyngeal nerve. The vagus contains afferent,
motor and parasympathetic fibres.
The afferent fibres of the vagus convey information
from:
■receptors for general sensation in the pharynx, larynx,
oesophagus, tympanic membrane, external auditory
meatus and part of the concha of the external ear
■ chemoreceptors in the aortic bodies and baroreceptors in
the aortic arch
■receptors widely distributed throughout the thoracic and
abdominal viscera.
Within the brainstem, afferents carrying general sensation
end in the trigeminal sensory nucleus, while visceral
afferents end in the nucleus solitarius.
The motor fibres of the vagus arise from the
nucleus ambiguus of the medulla. They innervate the
muscles of the soft palate, pharynx, larynx and
upper part of the oesophagusto control of speech
and swallowing.
The parasympathetic fibres of the vagus nerve originate
from the dorsal motor nucleus of the vagus, which lies
in the medulla immediately beneath the floor of the
fourth ventricle. They are distributed widely throughout
the cardiovascular, respiratory and gastrointestinal
systems.
PAIN SCALE
HEADACHE IMPACT TEST
• The Headache Impact Test (HIT) is a tool used to measure
the impact headaches have on your ability to function
on the job, at school, at home and in social situations.
• To communicate the severity of headache.
• This questionnaire was designed to help you describe and
communicate the way you feel and what you cannot do
because of headaches
MIDAS
The MIDAS (Migraine Disability Assessment)
questionnaire was put together to help you
measure the impact your headaches have on
your lifeand to find the best treatment for you.
Beck's Depression
Inventory
This depression inventory can be self-scored. The
scoring scale is at the end of the questionnaire.
Consists of 21 questions, max score 63 and minimum
score 0
The Pittsburgh Sleep
Quality Index
(PSQI)
is an effective instrument used to measure the
quality and patterns of sleep in the older
adult.
It differentiates “poor” from “good” sleep by
measuring seven domains: subjective sleep quality,
sleep latency, sleep duration,habitual sleep
efficiency, sleep disturbances, use of sleep
medication, and daytime dysfunction over the last
month.
Scoring of the answers is based on a 0 to 3 scale,
whereby 3 reflects the negative extreme on the
Likert Scale.
In scoring the PSQI, seven component scores are
derived, each scored 0 (no difficulty) to 3 (severe
difficulty). The component scores are summed
to produce a global score (range 0 to 21).
Higher scores indicate worse sleep quality.

Pittsburgh Sleep Quality Index (PSQI) website at

http://www.sleep.pitt.edu/content.asp?id=1484&subid=2316.
Neuromodulation
Neuromodulation is technology that acts directly upon nerves. It is the alteration—or modulation—of nerve activity by
delivering electrical or pharmaceutical agents directly to a target area.
They affect every area of the body and treat nearly every disease or symptom from headaches to tremors to spinal cord
damage to urinary incontinence.
Neuromodulation works by either actively stimulating nerves to produce a natural biological response or by applying
targeted pharmaceutical agents in tiny doses directly to site of action.
Neurostimulation devices involve the application of electrodes to the brain, the spinal cord or peripheral nerves.
A low-voltage electrical current passes from the generator to the nerve, and can either inhibit pain signals or stimulate
neural impulses where they were previously absent.

The way in which oxygen inhalation reduces headache pain is unknown. Researchers have shown that there is an
increased blood flow in the brain in both cluster and migraine headaches, although both headaches do not have the
same degree of increased flow. It has been shown that oxygen causes a marked decrease in cerebral blood flow that is
coincident with the reduced degree of pain in cluster headache.
They use 100 percent oxygen for eight to nine liters a minute for up to 30 minutes.

Nyeri kepala dipengaruhi oleh nucleus trigeminoservikalis yang merupakan nosiseptif

yang penting untuk kepala, tenggorokan dan leher bagian atas. Semua aferen nosiseptif
dari trigeminus, fasial, glosofaringeus, vagus dan saraf dari C1 – C3 beramifikasi pada grey
matter area ini
Cervicogenic headache: mechanisms, evaluation, and treatment strategies (Biondi
DM) The Journal of the American Osteopathic Association, April 2005, Vol. 105, 16S-
22S.
PAI
N“Nyeri adalah pengalaman sensorik dan Nyeri Nosiseptif
emosional yang tidak menyenangkan akibat stimulasi singkat, tdk timbul kerusakan jaringan
kerusakan jaringan, baik aktual maupun
potensial atau yang digambarkan dalam Nyeri Inflamatorik
bentuk kerusakan tersebut”. - Stimulasi kuat,kerusakan/ lesi jaringan atau
Pain is a complex interaction that involves: proses inflamasi
- Dapat bersifat spontan atau dibangunkan
1. Cognitive - Berguna utk proses penyembuhan
2. Emotional Nyeri Neuropatik
3. Behavioral adanya lesi sistem saraf perifer atau sentral

Nyeri Fungsional
-nyeri akibat abnormalitas sistem saraf pusat berupa
peningkatan sensitivitas thd berbagai stimuli
- dahulu dikenal dgn nyeri psikogenik
 NOCICEPTIVE PAIN
Noxius Pheripheral Stimuli Pain
Heat Autonomic Response
Witdrawal
Cold Reflex Brain

Nosiseptif Intense
Nociceptor
Mechanical
Force sensory neuron
Heat

Cold Spinal cord

Adaptif Inflammation
INFLAMANTORY PAIN
Spontaneous Pain
Pain Hypersensitivity
Macrophage Reduced Threshold : Aliodyna
Mast Cell Increased Response : Hyperalgesia
Neutrophil
Granulocyte Brain

Inflamasi Tissue Damage

Nociceptor
sensory neuron

Spinal cord

Nyeri
NEUROPATHIC PAIN
Spontaneous Pain
Pain Hypersensitivity
Brain

Neuropatik Peripheral Nerve

Damage

Spinal cord Injury

Maladaptif FUNCTIONAL PAIN

Spontaneous Pain
NOCICPTOR Pain Hypersensitivity
Brain

Fungsional NOCICPTOR
Normal Peripheral
Tissue and Nerves
NOCICPTOR Abnormal Central
Processing
 Persepsi :
interpretation of noxious stimuli
in sensori
cerebral cortex

Modulasi :
interaction of
internal analgesic (serotonin,
endorfin)
with noxious stimuli in
dorsal horn of medulla

Transmisi :
the way stimuli going through
A-d and C fibers to CNS
Sensitisasi nosiseptor :
Kulit,otot, tulang, saraf, dll
Tranduksi :
changing noxius stimuli
becomes electrical stimuli
Reseptor khusus yang
disebut nociceptors (orde 1)
Saraf aferen primer (saraf
A-delta dan C)
mentransmisikan stimulus
noxious ke CNS.

Kornu dorsalis medulla

Traktus asending nosiseptik
(orde 2)

Traktus thalamo-kortikalis
(orde 3) Sistem inhibitor
desenden
 Pathophysiology of Neuropathic
Pain
Peripheral mechanisms

Peripheral Neuron
hyperexcitability

Loss of Abnormal
inhibitory controls Discharges NeP
Central mechanisms

Central Neuron
hyperexcitability
(central sensitization)
ID
pain
 Signs and Symptoms of Neuropathic
Pain
Sign/Symptom Description (example)
Spontaneous symptoms
Persistent burning, intermittent
 Spontaneous shock-like or lancinating pain
pain1
Abnormal unpleasant sensations
 Dysesthesias2 e.g. shooting, lancinating, burning

 Parasthesias2 Abnormal, not unpleasant sensations e.g. tingling

Stimulus
-evoked
symptom
s
Painful response to a non-painful stimulus
 Allodynia2 e.g. warmth, pressure, stroking

Heightened response to painful stimulus e.g.

 Hyperalgesia2 pinprick, cold, heat

1. Baron. Clin J  Hyperpathia2

Pain. 2000;16:S12-S20. Delayed, explosive response to any painful stimulus
2. Merskey H et al. (Eds) In: Classification of Chronic Pain:
Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:209-212.
Positive and Negative Sensory Signs and Symptoms of Neuropathic Pain

Positive sensory signs Negative sensory signs

and symptoms and symptoms
• Dysesthesias  Loss / impairment of
• Paresthesias sensory quality
• Spontaneous pain*  Numbness and reduced
• Stimulus-evoked pain sensation

Sensory changes and pain may coexist

*Also known as stimulus-independent pain

Baron R. Clin J Pain. 2000;16:S12-S20.
Perifer Sensitisation
PERIPHERAL MECHANISMS
Peripheral nerve injury

1.Sensitization by spontaneous activity by

neuron, lowered threshold for activation,
increased response to given stimulus.
2.Formation of ectopic neuronal
pacemakers along nerve and increased
expression of sodium channels and
voltage gated calcium channels. (α 2 delta
subunit- where gabapentin acts)
3.Adjacent demyelinated axons can have
abnormal electrical connections channels
and increased neuronal excitability
Neuropathic Pain
Causes
• Peripheral causes of • Central causes of
neuropathic pain neuropathic pain
• Trauma
– Stroke
• e.g. surgery, nerve entrapment, amputation
• Metabolic disturbances – Spinal cord lesions
• e.g. diabetes mellitus, uremia
• Infections – Multiple sclerosis
• e.g. herpes zoster (shingles), HIV – CNS tumors
• Toxins
• e.g. chemotherapeutic agents, alcohol
• Vascular disorders
• e.g. lupus erythematosus, polyarteritis nodosa
• Nutritional deficiencies
• e.g. niacin, thiamine, pyridoxine
• Direct effects of cancer
• e.g. metastasis, infiltrative

Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999; Galer BS, Dworkin RH (Eds) A clinical guide to
neuropathic pain. 2000: Woolf CJ et al. Lancet. 1999;353:1959-1964.
 Central sensitization

After nerve injury, increased input to the dorsal horn Perceived pain DORSAL HORN MS:
can induce central sensitization 1. Terjadi perluasan
reseptor field size
sehingga neuron
Nerve lesion
Descending
spinalis akan
Ascending
input berespon terhadap
modulation
stimulus yang
normalnya tidak
Nociceptive afferent fiber
merupakan
stimulus nosiseptif.
Perceived pain
2. peningkatan
Abnormal discharges induce central sensitization (allodynia) besaran dan durasi
respon terhadap
Tactile
stimulus .
stimuli Descending Ascending 3. pengurangan
input
modulation
ambang batas
sehingga stimulus
yang secara normal
Intact tactile fiber tidak bersifat
nosiseptif akan
mentransmisikan
informasi nosiseptif
Pain Inhibitory Substances
• Endorfin dan Enkafalin
• Substansi endogen serupa opiod  inhibitor terhadap transmisi nyeri.
• Diaktifkan melalui aktifitas dari :
• Serabut perifer non nosiseptor yaitu serabut yang tidak mentransmisikan stimuli
nyeri, yang berada pada tempat reseptor yang sama dengan reseptor nyeri atau
nosiseptor.
• Serabut desenden, berkumpul bersama dalam suatu system yang disebut
descending control.
• Fungsi: Memblok transmisi impuls ini di dalam otak dan medulla spinalis.
• Keberadaan enkefalin dan endorphin menjelaskan bagaimana orang yang berbeda
merasakan tingkat nyeri yang berbeda dari stimuli nyeri yang sama.
• Kadar endorphin beragam berbeda2 diantara individu. Kadar endorphin yang banyak
lebih sedikit merasakan nyeri dan sebaliknya.
Pathophysiological Mechanisms Of Neuropathic Pain
Aδ or Aβ fibre

C-fibre

Skin
Spinal cord dorsal horn Skin

C-fibre
C-fibre
Opioid receptor Α2-δ subunit
NMDA receptor
NE/5HT receptor
Aδ or Aβ fibre Cytokine receptor
GABA receptor AMPA/KA receptor C-fibre
α-adrenoceptor
TRPV1 receptor
AMPA/KA receptor Chemokine receptor
Chemokine
receptor
Cytokine receptor
Sodium channel
Calcium Channel
(Α2-δ subunit) Baron et al., 2010
Lancet Neurology 2010;9:807-19