PATOFISIOLOGI SISTIM SARAF

(fungsi luhur)
Dan
Patofisiologi migren, TTH,
epilepsy

Lab. Fisiologi
Fakultas Kedokteran Universitas Brawijaya
Malang
1
Sindrom kortikal
Lob frontal
- Hemiparese
- Gaze parese
- Bangkitan kejang motorik
- Afasia motorik
Lob parietal
-sindrom hemisensorik
-bangkitan kejang sensorik
-aleksia,aparaxia
Sindrom kortikal
Lob temporalis
-afasia sensorik
- Defisit memori
- Bangkitan kejang psikomotor

Lob occipitalis
- Agnosia visual
- Hemianopia kontralateral
⚫Lobus limbik
⚫Halusinasi olfaktori
⚫Gangguan radiasi optik
⚫Homonim quadroanopia
⚫ Lesi destruktif pada superior posterior area temporal :
afasia Wernicke
memori
1.Memori sesaat (intermediate memory)
⚫Pasien mengingat informasi bersifat pendek setelah
membaca atau mendengar
⚫Contoh: nomor, kata sederhana
2.Memori jangka pendek ( short memory)
⚫Pasien mengingat suatu list atau nomer agak
komplek
⚫Contoh: alamat rumah, nomer telpon
3.Memori jangka panjang

⚫Contoh pengetahuan dasar

⚫Nama presiden dan wakil presiden, nama pubklik figur
⚫Atau inforamsi bpribadi nama anaknya, umur suami,
nama kakek atau alamat rumahnya
⚫Area Broca : area bahasa motorik (inferior lobus
frontalis)
⚫Area Wernicke : area bahasa perseptif (girus
temporal superior)
⚫Girus angularis : terdapat area bahasa perseptif
lobus parietalis
⚫Fasikulus arkuatus : penghubung area (subkortek)
 Wernicke’s and Broca Area

11 RETTY RATNAWATI 19112012

Gangguan berbahasa
⚫Afasia : gangguan berbahasa (lisan/tulisan) akibat
gangguan otak (vaskular, neoplasma, trauma,
infeksi, degeneratif,dll) yang mengenai area bahasa
⚫Right handed maka hemisfer kiri dominan (90-95%
populasi)
 afasia
⚫Afasia motoric
⚫Afasia sensorik
⚫Afasia global
⚫Afasia knduksi
⚫Afasia anomik

15
 Afasia motorik
⚫Kelancaran : tidak lancer
⚫Pemahaman : baik (tidak terganggu)
⚫Naming : terganggu
⚫Repitition: terganggu
⚫Reading: terganggu
⚫Writing : terganggu ( hemiparese )

16
 Afasia sensorik
⚫Kelancaran bicara: lancar
⚫Pemahaman: terganggu
⚫Naming : terganggu
⚫Repetition : terganggu
⚫Reading : terganggu
⚫Writing: terganggu

17
⚫Aleksia : gangguan membaca dan melihat (buta
kata/world blindnes)
⚫Kausa : Lesi girus angularis, atau hubungan kortek
visual
 Migren

19
diskirpsin
⚫Sakit kepala berulang dengan manifestasi serangan
- Antara 4 – 72 jam
- Tipe sakit kepala unilaterala
- Pulsating quality
- Intesitas sedang sampai berat
- Memberat dengan aktivitas fisik yang rutin
- Diserta mual muntah dan atau photophobia dan
phonophobia
Perjalanan migren
⚫1/3 px migren mendapat serangan lebih dari 4 hari/bln
⚫6% mendapat serangan lebih dari 14 hari /bulan
⚫Episodik :< 15 headache days/month
⚫Chronik:>= 15 headache /month, selama 3 bulan
⚫Episodik menjadi kronik: chronification
⚫Chronic menjadi episodic
Faktor yang mempengaruhi cronisitas
(chronification)
⚫Faktor comorbid: depresi,
anxietas,obesitas,asma,snoring,adanya sakit kepala lain
⚫Faktor eksogen: stressfull live events,head
injury,caffeine
⚫Faktor karakter sakit kepala individu tsb: frekunsi
serangan,ada nya mual,alodenia
⚫Medikamentosa: MOH,treatment yg tdk efektif
Klasifikasi
∙ 1.1 Migraine without aura
∙ 1.2 Migraine with aura
∙ 1.3 Chronic migraine
∙ 1.4 Complications of migraine
⚫ 1.5 Probable migraine
⚫ 1.6 Episodic syndromes that may be associated with migraine
dx
⚫According to the International Headache Society, the diagnosis of migraine
requires that the patient has experienced at least 5 attacks that fulfill the
following 3 criteria and that are not attributable to another disorder.  [1]
-  First, the headache attacks must have lasted 4–72 hours (untreated or
unsuccessfully treated).
- -Second, the headache must have had at least 2 of the following
characteristics:
∙ Unilateral location

∙ Pulsating quality

∙ Moderate or severe pain intensity

∙ Aggravation by or causing avoidance of routine physical activity (eg,

walking or climbing stairs)

-Third, during the headache the patient experiences at least 1 of the
following:
∙ Nausea and/or vomiting

∙ Photophobia and phonophobia

 etiologi
⚫ Migraine has a strong genetic component. Approximately 70% of migraine patients have a first-degree relative with
a history of migraine
⚫Migraine precipitants
⚫Various precipitants of migraine events have been identified, as follows:
∙ Hormonal changes, such as those accompanying menstruation (common), [44] pregnancy, and ovulation
∙ Stress
∙ Excessive or insufficient sleep
∙ Medications (eg, vasodilators, oral contraceptives [45] )
∙ Smoking
∙ Exposure to bright or fluorescent lighting
∙ Strong odors (eg, perfumes, colognes, petroleum distillates)
∙ Head trauma
∙ Weather changes
∙ Motion sickness
∙ Cold stimulus (eg, ice cream headaches)
∙ Lack of exercise
∙ Fasting or skipping meals
∙ Red wine
⚫Certain foods and food additives have been suggested as potential precipitants of migraine, including the following:
∙ Caffeine
∙ Artificial sweeteners (eg, aspartame, saccharin)
∙ Monosodium glutamate (MSG)
∙ Citrus fruits
∙ Foods containing tyramine (eg, aged cheese)
∙ Meats with nitrites
patogenesa
1.Vascular theory
⚫ ischemia induced by intracranial vasoconstriction is responsible for the aura of migraine and that the
subsequent rebound vasodilation and activation of perivascular nociceptive nerves resulted in
headache.
⚫This theory was based on the following 3 observations:
∙ Extracranial vessels become distended and pulsatile during a migraine attack
∙ Stimulation of intracranial vessels in an awake person induces headache
∙ Vasoconstrictors (eg, ergots) improve the headache, whereas vasodilators (eg, nitroglycerin) provoke
an attack
However, this theory did not explain the prodrome and associated features. Nor did it explain the
efficacy of some drugs used to treat migraines that have no effect on blood vessels and the fact
that most patients do not have an aura. Moreover, with the advent of newer imaging technologies,
researchers found that intracranial blood flow patterns were inconsistent with the vascular theory.
⚫ No consistent flow changes have been identified in patients suffering from migraine headache without
aura. Regional cerebral blood flow (rCBF) remains normal in the majority of patients.

⚫ However, bilateral decrease in rCBF, beginning at the occipital cortex and spreading anteriorly, has
been reported. More recently,
2.Neurovascular theory
⚫] According to this theory, migraine is primarily a neurogenic process with secondary changes
in cerebral perfusion. [12]
⚫ 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.
⚫ Cortical spreading depression
-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.
⚫ 
 oligemia
3.oligemia

⚫Positron emission tomography (PET) scanning demonstrates that blood flow is moderately
reduced during a migrainous aura, but the spreading oligemia does not correspond to
vascular territories. The oligemia itself is insufficient to impair function. Instead, the flow is
reduced because the spreading depression reduces metabolism.
⚫Although CSD is the disturbance that presumably results in the clinical manifestation of
migraine aura, this spreading oligemia can be clinically silent (ie, migraine without aura).
Perhaps a certain threshold is required to produce symptoms in patients having aura but not in
those without aura.
4.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.
⚫ 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
terapi
⚫Migraine treatment involves acute (abortive) and preventive
(prophylactic) therapy. Patients with frequent attacks usually
require both. Measures directed toward reducing migraine triggers
are also generally advisable.
⚫ Acute treatment aims to reverse, or at least stop, the progression
of a headache that has started.
⚫ Preventive treatment, which is given even in the absence of a
headache, aims to reduce the frequency and severity of the
migraine attack, make acute attacks more responsive to abortive
therapy, and perhaps also improve the patient's quality of life
Moderate Severe Extremely Severe

NSAIDs Naratriptan DHE (IV)

Isometheptene Rizatriptan Opioids

Ergotamine Sumatriptan (SC,NS) Dopamine antagonists

Naratriptan Zolmitriptan Lasmiditan

Rizatriptan Almotriptan  

Sumatriptan Frovatriptan  

Zolmitriptan Eletriptan  

Almotriptan DHE (NS/IM)  

Frovatriptan Ergotamine  

Eletriptan Dopamine antagonists  

Dopamine antagonists Lasmiditan  

DHE=Dihydroergotamine; NSAIDs=nonsteroidal anti-inflammatory drugs

The following mayTherapy
Prophylactic be considered indications for prophylactic migraine therapy:
∙ Frequency of migraine attacks is greater than 2 per month
∙ Duration of individual attacks is longer than 24 hours
∙ The headaches cause major disruptions in the patient’s lifestyle, with significant disability that lasts 3
or more days
∙ Abortive therapy fails or is overused
∙ Symptomatic medications are contraindicated or ineffective
∙ Use of abortive medications more than twice a week
∙ Migraine variants such as hemiplegic migraine or rare headache attacks producing profound
disruption or risk of permanent neurologic injury

⚫The goals of preventive therapy are as follows:

-Reduce attack frequency, severity, and/or duration
-Improve responsiveness to acute attacks
-Reduce disability
 Table 2. Preventive Drugs for Migraine (Open Table in a new window) Beta blockers
Tricyclic antidepressants
High efficacy
Divalproex
First line Topiramate

Low efficacy Verapamil

Methysergide
Flunarizine
 
MAOIs
High efficacy
CGRP inhibitors
Second line Botulinum toxin

  Cyproheptadine
Unproven efficacy Gabapentin

MAOIs = monoamine oxidase inhibitors

Comorbid Condition Medication

Hypertension Beta blockers

Angina Beta blockers

Stress Beta blockers

Table 3. Preventive Medication for Comorbid Conditions (Open Table in a new window)

Depression Tricyclic antidepressants, SSRIs

Overweight Topiramate, protriptyline

Underweight Tricyclic antidepressants (nortriptyline, protriptyline)

Epilepsy Valproic acid, topiramate

Mania Valproic acid

SSRIs = selective serotonin reuptake inhibitors

 TENSION TYPE HEADACHE

35
- Nyeri kepala : rasa nyeri atau tidak enak pada bagian
atas kepala dari orbita sampai ke oksipital
- Tension type headache: rasa nyeri dalam seperti tertekan
berat atau terikat erat,umunya bilateral yang pada
awalnya timbul secar episodik dan terikat dengan stress
dan berkembang nyaris muncul setiap hari dalam bentuk
kronis tanpa ada lagi kaitan psikologis yang jelas
- Sinonim :muscle contraction headache,psycomyogenic
headache
- 90% populasi pernah mengalami TTH
Etiologi
1.Disfungsi oromandibuler
2.Strees psikogenik
3.Anxietas
4.Depresi
5.Stress otot
6.Kelebihan obat pereda nyeri
⚫ Gambaran klinis
- Adanya nyeri kepala
- Tanpa adanya kelainan yang jelas selain kontraksi otot berlebihan
- Nyeri terasa bilateral, denga terlokalisir di kepala bagian depan,
temporal,belakang kepala,leher,punggung atas, bisa pula disertai
gangguan tidur (kronis)
- Tidak berdenyut
- Muncul perlahan selama beberapa jam kemudian terus
berlangsung selama beberapa hari
- Nyeri kepala seperti diikat,ditekan kuat
- Keluhan membaik dengan kompres hangat atau masage
Klasifikasi
1.TTH episodik infrequent
2.TTH episodik yang frequent
3.TTH kronik
4.Probable tension type headache
Diagnosa
1.TTH infrequent
a.Paling tidak terdapat 10 episode serangan dengan rata-rata < 1hari/bulan (< 12 hari/tahun)
dan memenuhi kriteria B-D
b.Nyeri kepala berlangsung 30 mnt sampai 7 hari
c.Nyeri kepala paling tidak terdapat 2 gejala khas:
1.Lokasi bilateral
2.menekan/mengikat
3.Intensitas ringan atau sedang
4.Tidak diperberat oleh aktivitas rutin seperti berjalan atau naik tangga
d.Tidak didapatkan:
1.Mual dan muntah
2.Lebih dari 1 keluhan : foto fobia atau fonofobia
f.Tidak terkait dengan kelainan lain
TTH frequent
a.Paling tidak terdapat 10 episode serangan dalam 1-15 hari/bulan selama
paling tidak 3 bulan (12-180 hari/tahun) dan memenuhi kriteria b-d
B.Nyeri kepala berlangsung 30 menit sampai 7 hari
c.Nyeri kepala paling tidak terdapat 2 gejala khas:
1.Lokasi bilateral
2.menekan/mengikat
3.Intensitas ringan atau sedang
4.Tidak diperberat oleh aktivitas rutin seperti berjalan atau naik tangga
d.Tidak didapatkan:
1.Mual dan muntah
2.Lebih dari 1 keluhan : foto fobia atau fonofobia
e.Tidak terkait dengan kelainan lain
TTH kronik
a.Nyeri kepala timbul ≥ 15 hari/bulan,berlangsung > 3 bulan (≥ 180
hari/tahun) dan juga memenuhi kriteria b-d
b.Nyeri kepala berlangsung beberapa jam atau terus menerus
c.Nyeri kepala paling tidak terdapat 2 gejala khas:
1.Lokasi bilateral
2.menekan/mengikat
3.Intensitas ringan atau sedang
4.Tidak diperberat oleh aktivitas rutin seperti berjalan atau naik tangga
d. Tidak didapatkan:
1.Lebih dari satu : fotofobia,fonofobia,atau mual ringan
2.Mual sedang atau berat maupun muntah
e.Tidak ada kaitan dengan penyakit lain
patofis
⚫ Iskemi dan meningkatnya kontraksi otot-otot di kepala dan leher
diduga penyebab TTH
⚫ Riset terbaru membuktikan peningkatan substansi endogen di
otot trapezius penderita tipe frequent episodic TTH. Juga
ditemukan nitric oxide sebagai perantara (local mediator) TTH
⚫ Mekanisme myofascial perifer berperan penting pada TTH
episodik,
⚫ sedangkan pada TTH kronis terjadi sensitisasi central nociceptive
pathways dan inadequate endogenous antinociceptive circuitry.
⚫ Sensitisasi jalur nyeri (pain pathways) di sistem saraf pusat karena
perpanjangan rangsang nosiseptif (prolonged nociceptive stimuli)
dari jaringan-jaringan miofasial perikranial tampaknya
bertanggung-jawab untuk konversi TTH episodik menjadi TTH
kronis
gbr
TATALAKSANA
⚫Simtomatik
- Lebih efektif bila diberikan segera setelah kejadian
TTH
- Bisa dengan NSADs, paracetamol, atau kombinasi
- Terapi simtomatik diberikan sebanyak 2-3 kali per
minggu dan maksimal 2 dosis per hari
- Terapi preventif di berikan pada pasien dengan
peningkatan frekuensi dan durasi nyeri kepala atau
penderita dengan disabilitas
Tx farmakologi
⚫Paracetamol dosis 1000mg atau aspirin dosis 1000mg
⚫NSADs : ibuprofen 800mg,sodium naproxen
825mg,lumiracoxib (200mg at 400mg),diklofenak
12,5mg dan 25mg
⚫Metamizole 500mg / 1000mg
⚫Kombinasi analgesic, cafein dan sedative atau
transquiliser cukup efektif
Tx profilaksis
⚫Diberikan pada TTH kronik dan frekuens episodic
TTH,dengan memperhatikan komorbid (depresi/cemas)
⚫Diberikan pada kasus disabilitas akibat nyeri kepala > 4
hari /bln atau tidak ada respon terhadap tx simtomatik
⚫Tx dikatakan efektif bila mengurangi frekuensi serangan
atau derajat keparahan minimal 50%
⚫Dalam tx profilak perlu identifikasi factor pencetus dan
factor yg menguranginya
⚫Tx ini idealnya berbasis tunggal yg di titrasi pada dosis
rendah yg efektif dan di toleransi dengan baik
Obat untuk profilaksis;
1.Amitriptilin (antidepresan), dosis 10-25mg
2.Mirtazapin 30mg
3.Venlafaxin 150mg
4.maprotilin75mg
Tx non farmakologi
⚫EMG biofeedback
⚫Cognitif behaviour therapy
⚫Latihan relaksasi
⚫Akupuntur dan blok saraf
 EPILEPSI

50
 Epilepsi
Definisi secara konseptual
• Kelainan otak yang ditandai dengan kecenderungan untuk menimbulkan
bangkitan epileptik yang terus menerus dengan konsekuensi
neurobiologis,kognisi,psikologi,sosial
Definisi praktis

• Minimal ada 2 bangkitan unprovoked atau 2 bangkitan refleks dengan

jarak waktu antar bangkitan lebih dari 24 jam
• Satu bangkitan unprovoked/1 bangkitan refleks dengan kemungkinan
terjadinya bangkitan dalam 10 thn kedepan sama dengan bila ada 2
bangkitan unprovoked
• Sudah tegak sindrome epilepsi
 klasifikasi

52
Penegakan diagnosa epilepsi
1. Memastika kejang epileptik atau non epileptik
2. Memastikan kejang /bangkitan epileptik tersebut unprovoked
3. Memastikan adanya bangkitan unprovoked tersebut berulang
minimal 24 jam
4. Menentukan bentuk kejang /bangkitan epilepsi
5. pemeriksaan fisik untuk menemukan defisit neurologi
6. pemeriksaan EEG
7. pemeriksaan pencitraan otak, terutama kejang yang muncul pertama
usia dewasa
 Terapi epilepsi
Tujuan tx epilepsi Waktu memulai tx

Bebas bangkitan Diagnosa sudah tegak

Ada minimal 2 x kejang dalam

Tanpa efek samping OAE
setahun
Px dan keluarga sudah
dijelaskan tentang tujuan
pengobatan
 Prinsip tx epilepsi

1.Tx di mulai dengan monoterapi,menggunakan OAE

pilihan utama sesuai bangkitan
2.Dosis rumatan OAE yg memadai
3. OAE dimulai dengan dosis rendah naik secara bertahap

4. Hindari faktor pencetus

5.Pemberian asam folat 1-5 mg/hari, terutama wanita usia
reproduktif
 Semoga bermanfaat

58