BRAIN TUMOR

dr. Fidha Rahmayani, M.Sc, Sp.S

Bagian Neurologi FK Unila/ RS Abdul Muluk
 Kasus
Seorang wanita 40 tahun datang dengan keluhan
utama nyeri kepala kronik. Sejak 3 bulan
sebelumnya pasien sering mengeluh nyeri kepala
berdenyut di seluruh kepala yang semakin lama
semakin memberat. Nyeri kepala terutama
dirasakan memberat saat pasien mengedan buang
air besar dan batuk. 1 bulan terakhir pasien mulai
mengalami kelemahan pada anggota gerak
sebelah kiri. Pasien memiliki riwayat KB hormonal
sejak usia 30 tahun.
 INTRACRANIAL TUMORS

Acoustic Other
Neurinoma 9%
8% Metastasis
33%
Pituitari
adenoma
10%

Meningioma Glioma
15% 25%
The different types of brain tumors include the following:
:
A. Primary Benign Tumors of the Brain
a) Acoustic neuroma rare
b) Meningioma 19%
c) Pituitary adenoma 10%
d) Craniopharyngioma 5%
e) Pineal gland tumor 1%

Neurological Dysfunction
•May affect speech, memory, vision
•Localized weakness or sensory loss due to
invasion or compression of adjacent brain
tissue
•The resultant neurologic loss dependant on
the location of the tumor
B. Metastatic Tumors of the Brain

a) Metastatic carcinomas (60% lung, 30% breast)

b) Meningeal carcinomatosis

C. Primary Malignant Tumors of the Brain

1. Gliomas (Most common type of primary tumor)
a) Low Grade Astrocytoma 25%
b) High Grade Astrocytoma 10%
c) Ependymoma 6%
d) Oligodendrocytoma 5%
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 Tabel 1. Tipe Tumor Jaringan Saraf
Tumor Persentase
Glioma (41%)
Glioblastoma multiforme 20
Astrocytoma 10
Ependymoma 6
Medulloblastoma 4
Oligodendrocytoma 5
Meningioma (17%) 15
Pituitary adenoma (13%) 7
Neurinoma (Schwannoma) (12%) 7
Metastatic carcinoma 6
Craniopharyngioma, dermoid, epidermoid, teratoma 4
Angioma 4
Sarcoma 4
Unclassified (mostly glioma) 5
Miscellaneous (pinealoma, chordoma, granuloma, lymphoma) 3
Total 100

Sumber: Victor & Ropper, 2002.

 ETIOLOGI
Berhubungan dengan :
• Therapi radiasi
Baik pada dosis tinggi maupun rendah
• Hormone sex
Sekitar 2/3 tumor mengekspresikan
reseptor Progesterone
• Genetik
– Kehilangan kromosom 22
– Mutasi gen NF2
 Etiologi tumor
• Perubahan dari protoonkogen menjadi
onkogen
• Penurunan tumor suppressor gen
• Peningkatan gen controlling growth factor
• Herediter (misalnya peningkatan tumor
otak pada neurofibromatosis dan
tuberoussklerosis)
• Trauma
• Infeksi
• Radiasi
 Etiologi dan Faktor Resiko
• Genetik
– Familial
• Lingkungan
– Radiasi
– Trauma kapitis berat
– Paparan Kronis bahan petrokimia
STRUKTUR SEL NORMAL
• Membran sel
• Sitoplasma
• Inti atau nukleus

SEL TUMOR MALIGNA

• Mitosis lebih cepat
• Produksi enzim colagenase IV
• Kemampuan produksi zat kimia
(angiogenesis factor)
LOKASI TUMOR
GANGGUAN BERDASARKAN LOKASI TUMOR
Symptom and Sign of Brain Tumor Based on Its
Location ( Flower, 2000)
 Gejala Tumor Otak
Ciri utama dari tumor otak ada 4 yaitu:
1. defisit neurologis progresif (68%)
– Destruksi-kompresi langsung/ tidak
langsung
– Akibat masa dan edema
2. motor weakness (45%)
3. headache (54%)
4. seizure (26%)
(Greenberg, 2001)
 Gejala Tumor otak (Crow, 2001)
Def. Neurologis Nyeri kepala Kejang (15-
progresif (70%) (>50%) 20%)

-Destruksi atau
Memburuk di Gangguan
kompresi langsung
pagi hari eksitabilitas neural
-Kompresi akibat
massa, edema

-Invasi atau kompresi

-TIK tinggi
-Sekunder atau
psikogenik
 MEKANISME
TANDA KLINIK TUMOR
1. Kompresi pd jaringan neuronal
2. Infiltrasi / invasi langsung pd jar neuronal
3. Gangguan pembuluh darah
4. Gangguan eksitabilitas
5. Penekanan efek massa
6. Gangguan sirkulasi aliran LCS
(Spencer, 1989)
 Sign and Symptom Tumor Tumor
Supratentorial infratentorial
• Headache + +
• Nausea / vomitus + +
• Papiledema + ++
• Kejang + -
• Gangguan fungsi luhur ++ +

• Ataxia dan gangguan gait - ++

• Vertigo dan nistagmus - ++

• Diplopia + ++
• Ataksia, dismetria, tremor, - +
gangguan koordinasi
• Multicranial nerve palsy - +

• Kelemahan motorik, ++ -
gangguan endokrin
 GEJALA DAN TANDA TUMOR
SUPRATENTORIAL
• Yang berkaitan dengan TIK :
* Dari efek massa tumor dan atau edema
* Dari blokade aliran LCS (hidrocefalus)
jarang pada terjadi
• Defisit fokal : kelemahan, disfasia (37-58% pada
tumor otak di hemisfer kiri.
* Destruksi jaringan otak karena infasi tumor
* Kompresi jaringan otak oleh massa dan atau
edema peritumorald/a perdarahan
* Kompresi saraf kranial
 GEJALA DAN TANDA TUMOR
INFRATENTORIAL

Tanda dan gejala efek massa:

* Lesi di hemisfer serebelum: ataksia
ekstremitas, dismetria, tremor
* Lesi di vermis serebelum: ataksia badan
* Batang otak : biasanya melibatkan
multipel saraf kranial dan gangguan
traktus, nistagmus.
 INFRATENTORIAL TUMOR
Peningkatan TIK karena hydrosefalus:
• Nyeri kepala
• Mual / muntah : akibat peningkatan TIK dari
hydrosefalus atau penekanan langsung pada
nukleus vagal atau area postrema (pusat
muntah)
• Papilledema
• Ataxia / ggn berjalan
• Diplopia: n.VI palsy (penekanan langsung
pada nervus VI)
• Vertigo
(Greenberg, 2001)
 Types of Brain Tumors
• Meninges: meningioma, hemangiopericytoma
• Glia: astrocytoma, oligodendroglioma, ependymoma,
choroid plexus papilloma..
• Vascular: hemangioblastoma.
• Primitive cells: neuroblastoma, germinoma,
medulloblastoma, pineoblastoma, retinoblastoma
• Neuronal: ganglioglioma, gangliocytoma
• Pituitary: adenoma, craniopharyngioma
• Nerves: schwannoma, neurofibroma
NYERI KEPALA PADA TUMOR OTAK
Penyebab  kombinasi dari:
1. Peningkatan TIK karena:
a. Efek massa tumor
b. Hidrosefalus (obstruktif maupun komunikans)
c. Efek massa karena edema
d. Efek masa karena hemorhage
2. Invasi/kompresi bangunan peka nyeri : duramater,
pembuluh darah, periosteum
3. Sekunder gangguan penglihatan:
a. diplopia, terjadi akibat disfungsi otot ekstraokuler :
III,IV,VI, TIK, inernuklear oftalmoplegi karena ggn
brainstem
b. kesulitan focusing disfungsi nervus optikus
4. Ekstrim hipertensi krn kenaikan Tekanan intra
kranial
5. Psikogenik: stress krn kehilangan kemampuan
fungsional
KARAKTERISTIK
NYERI KEPALA SOP
(Dodick, 1997)

1) Tidak terlokalisir dengan baik

2) Perjalanan penyakit subakut
progresif
3) Intensitas sedang sampai berat
4) Resisten terhadap analgetik biasa
KARAKTERISTIK
NYERI KEPALA SOP (Greenberg, 2001)
1) memberat pada pagi hari
(akibat hipoventilasi selama tidur)
2) memberat dengan batuk, ketegangan
3) kepala harus diposisikan tertentu (30%
kasus)
4) disertai dengan mual dan muntah (40%
kasus)
( stl muntah, akibat hiperventilasi)
5) Tipe nyeri kepala:
i. 77% menyerupai nyeri kepala tension type
headache,
ii. 9% menyerupai migraine.
iii.8% merupakan nyeri kepala tumor
Penyebab nyeri kepala pagi pada TIK
meningkat :

• Peninggian pCO 2 selama tidur karena

depresi pernapasan, sehingga terjadi
vasodilatasi, peninggian volume darah
intrakranial serta pembengkakan otak
yang berakibat perburukan pada traksi
atau pergeseran pembuluh darah.
• Penurunan reabsorpsi cairan
serebrospinal.
• Posisi berbaring pada malam hari.
Tanda-tanda Tekanan Intrakranial (TIK) meningkat:

• Trias klasik : nyeri kepala, muntah,

edem papil
• Tanda lain : bradikardi, peninggian
tekanan darah sistemik, dilatasi
pupil, ptosis bilateral, gangguan
upgaze, ekstensi terhadap nyeri,
pernapasan irreguler dan
mengantuk.
Increase Intracranial Pressure
 CAUSES of RAISED
INTRACRANIAL PRESSURE

HYDROCEPHALUS BRAIN ‘SWELLING’

MASSES
TUMOURS
ABSCESS
CYSTS
HAEMATOMAS
Cerebral oedema This is an abnormal accumulation of fluid
in the cerebral parenchyma.It is usually the result of
breakdown of the blood–brain barrier, and it may occur
following damage initiated by several different
causes:Ischaemia, e.g. from infarction.Trauma,e.g.
from head injury.Inflammation encephalitis or meningitis.
Oveproduction of CSF by choroid plexus neoplasms
 Edem serebri vasogenik merupakan akibat primer dari
meningkatnya permeabilitas blood brain barier

Edem serebri sitotoksik terjadi sekunder dari kerusakan

elemen seluler serebri, terlepasnya faktor-faktor toksik
dari netrofil dan bakteri. Sehingga terjadi peningkatan
kandungan air intraseluler, dimana terjadi kebocoran
potasium, glukosa digunakan melalui glikolisis anae
robik, produksilaktat.

Edem serebri interstitial terjadi sekunder dari obstruksi

aliran LCS akibat inflamasi ruang subarakhnoid, seperti
hidrosefalus.
 EDEMA CEREBRI PADA TUMOR
• Vasogenic edema
- Increased permeability of the capillary
endotelial cells plasma protein enter
the extracellular space
- Defect of the endothelial cell junction
- Microvascular transudative factors
*protease released by tumor cells
 weakening BBB
1. MENINGIOMA
Meningioma
 EPIDEMIOLOGY

• 14,3%-19% of Primary Intracranial

Tumors
• Peak Incidence: 45 years age
• Female : male ratio= 1,8 : 1
• In childhood & adolescene= 1,5%
 MENINGIOMA

• benigna
• arise from arachnoid cap cells (not dura)
• located along falx, convexity, sphenoid bone
• Adult
• slow growing
• circumcribed ( non-infiltratating)
• caused hyperostosis of bone
• epilepsy >>
• may be asymtomatic
• tx –> total resection
• good prognosis
A. 3 main categories of ‘classic meningiomas’
• Meningotheliomas / angiomatous
• Fibrous or fibroblastic
• Transtitional
Varian : microcystic, psammomatous,
myxomatous, xanthomatous, lipomatous,
granular, secretory, chondroblastic,
osteoblastic, melanotic
B. Angioblastic : hemangioblastoma
C. Atypical meningioma
D. Malignant meningiomas : anaplastic,
papilary or sarcomatous
Types of meningiomas exist based on
malignant behavior (WHO1993):

Benign (grade I) with a recurrence rate of

6.9%: Despite invasion of the adjacent bony
structures, grade I meningiomas do not
invade the brain parenchyma.

Atypical (grade II) with a recurrence rate of

34.6%: This type of meningioma shows
frequent mitosis and an increased nuclear-
cytoplasmic ratio.

Malignant (grade III and IV) with a recurrence

rate of 72.7%: This type of meningioma shows
even greater mitosis, necrosis, and invasion of
brain parenchyma.
 TANDA & GEJALA
• Tidak terdapat tanda tunggal atau
spesifik untuk meningioma
• Kadang asimptomatis
• Tumor terdeteksi secara tidak sengaja
• Gejala: headache, paresis, seizure,
personality change, confusion, visual
impairment
 TANDA & GEJALA
sesuai lokasi
• Olfactory groove: anosmia
 triad Foster Kenedy symdrome (anosmia,
papiledema kontralateral, dan atropi nervus
optikus)
• Tuberculum sellae: chiasmal syndrome,
bitemporal hemianopia
• Cavernous sinus: diplopia, parese n. III
• Foramen Magnum: nunchal & suboccipital pain
 How is a brain tumor diagnosed?

In addition to a complete medical history and

physical examination, diagnostic procedures for
brain tumors may include the following:
1. Neurological examination - your physician tests
reflexes, muscle strength, eye and mouth
movement, coordination, & alertness.
2. CT scans are more detailed than general x-rays,
MRI
3. Spinal tap (Also called a lumbar puncture.)
 Treatment
• Supportive Pasien :
– Corticosteroid •Supportive
– Anticonvulsant  dexametason 4x1 amp
• Definitive  ranitidin 2x1 amp
– Surgery
•Definitive
– Radiation
 Rencana operasi
– Radionecrosis
– Chemotherapy

Greenberg, 2001
Treatment method for Brain Tumor (Flower, 2000)
 CORTICOSTEROID

• Primarily to treat vasogenic cerebral

edema
• Effective in tumors, meningitis, other
cerebral lesion that increase BBB
permeability
 CORTICOSTEROID

• Reduction in peritumor edema :

• decreased endothelial cell permeability by
stabilizing the endothelial cell membrane
• Increased clearance or resolution of
cerebral edema
• Inhibition of tumor cell growth
• Initial: dexamethasone 10mg IV  4mg / 6
hours
 Mannitol
1. Lowering ICP : Immediate plasma expansion :
reduce the hematocrit and blood viscosity
(improved rheology) which increases CBF and
O2 delivery. Osmotic effect : increased serum
tonicity draws edema fluid from cerebral
parenchyma.
2. Supports the microcirculation by improving
blood rheology
3. Possible free scavenging
(Greenberg,2000)
Dose : 0,5 – 1,0 g/kg body weight (Adam,et al., 2001)
Iv bolus 100 ml of 20 % mannitol over 15 minutes
(Lindsay, et al., 1997)
• A centrally-acting analgesic  bind to mu-opioid
receptors and inhibit the reuptake of
norepinephrine (NE) and serotonin
• Tramadol memiliki enantiomers (+) dan (-) yang
menunjukkan interaksi sinergis menghsilkan
antinosiseptik.
• Enantiomer (+) lima kali lebih poten dalam uptake
5- hydroxytryptamine (5-HT) dan memiliki afinitas
>> untuk berikatan dengan reseptor mu jika
dibanding uptake NE
• Enantiomer (-) lima-sepuluh kali lebih poten
menghambat uptake NE dan kurang affinitasnya
untuk berikatan dengan reseptor mu.
• Electrophysiologi: depresses motor and
sensory responses of the spinal nociceptive
system by a spinal and a supraspinal action.
• It has been estimated that the analgesic
potency of tramadol is one-tenth that of
morphine
Prognosis tumor intracranial
Tergantung :
- jenis tumor
- lokasi tumor
- ukuran tumor
- pertumbuhan tumor (cepat/lambat)
- efek pembedahan / radiotheraphy
Prognosis greatly depends on all of
the following :
•type of tumor •your tolerance of
specific medications,
•extent of the disease procedures, or
therapies
•size and location of
the tumor
•the tumor’s response
•presence or absence of to therapy
metastasis

•your age, overall •new developments in

health, and medical treatment
history
2. Cerebral Gliomas
Cerebral Gliomas
Astrocytic Tumors
Glioblastoma Multiforme
• Age: 45-55
• Male:female 2:1
• 20% of all Intracranial tumors
• 50-55% 0f all cerebral gliomas
• Ring-like enhancement on MRI
• Butterfly when it crosses the corpus
callosum
• Tx: Surgical resection, XRT,chemo
• Mean survival:
– 6 months without treatment
– 1 year with treatment
Gliobastoma Multiforme
Intraventricular Tumors
Nerve Sheath and Meninges
• Schwannoma
– Acoustic schwannomas most common
– Bilateral in NF2
• Neurofibroma
– NF1
• Meningioma
– 15% of all intracranial tumors
– 25% of all intraspinal tumors
Spinal Schwannoma
 3. Metastatic Tumors
• Most common infratentorial tumor in adults
• 80% are supratentorial
• Gray-white junction with vasogenic edema
• 50% appear solitary at presentation
• Leptomemingeal carcinomatosis
• Spinal cord compression
Brain Metastasis (MRI)
Relative Prevalence of
Intracranial Tumors
ETIOLOGY PRIMARY TUMOR

• Tumor paru 48%  83% lebih

• Tumor mammae 17%
• Genitourinary
• Colon dan Rectum
• Prostat
• Tiroid
• Cavum nasal
 Metastatic tumors (The mecanism)

•In adults, metastatic brain tumors are the most

common type of brain tumors.
•These are tumors that begin to grow in another part
of the body, then spread to spread to the brain
through the bloodstream.
•Often, a patient may have multiple metastatic tumors
in several different areas of the brain.
•Lung, breast, and colon cancers frequently travel to
the brain, as do certain skin cancers.
 Metastatic Disease

The spine and it surrounding

elements have a generous
blood supply, draining many
of the structures of the lower
abdominal cavity via a system
of veins called Batson's
Plexus. This venous plexus is
felt to be the reason that
certain intra-abdominal and
pelvic tumors have a tendency
to spread to the spine.
Batson’s venous plexus
 Definitions Metastasis
• Single metastasis:
– One brain metastasis regardless of
systemic/extracranial disease
• Solitary metastasis:
– Single brain met that is the only known cancer
in the body
 Diagnosis
• Imaging:
– MRI brain with gadolinium
• Staging of systemic disease:
– Chest, abdominal imaging if no known
primary
– In known systemic disease, activity of
extracranial mets highly relevant to treatment
 Approach to Treatment
• Medical treatment
• Surgery
• Radiation
• Chemotherapy
• Palliative treatment
 Approach to Treatment
 The most important factors determining
the options for treatment of brain
metastases are:
 Number of metastases
 Control of the primary tumor
 Extent of the extracranial metastases
 Age
 Performance Status (Karnovsky)
 Medical treatment
• Anticonvulsants
– When seizures are a symptom of disease
– Little role as prophylaxis
• Steroids
– Important in management, help relieve
symptoms of mass effect
– Minimize long term use given side effects
 Surgical treatment
• Biopsy:
• Open brain biopsy
• Stereotactic biopsy
– Frame-based: BRW, CRW, Leksell
– Frameless
– Advantage:
• Diagnosis:
– No known primary
– Known primary – Important role for bx
• Low morbidity
 Surgery
• Tumor resection best recommended in:
– Surgically accessible lesions, particularly if >3cm
– Symptomatic lesions with evidence of mass effect
– Posterior fossa lesions
– single, accesible brain met with no LM dissemination
– life expectancy > 3mths
– Karnofsky >70
– not a radiosensitive tumour (e.g., small cell)
 Biopsy or Resection?
Biopsy indicated for:
– Deep lesions
– Multiple lesions
– Patients otherwise too debilitated, medically
unfit
– Poor Karnofsky performance score
 Radiation

• Whole Brain radiation

• Radiosurgery
 Chemotherapy
– Effectiveness of chemotherapeutic agents
depends on
• Ability to treat specific tumor
• Ability to cross the BBB
– Timozolamide
• Alkylating agents with better BBB penetration
• Additive/synergistic activity in combination with
other chemo agents
 Prognosis

• Secara umum adalah buruk

• Survival rata-rata 1 bulan untuk
pasien yang tidak diterapi
• Survival sampai 2 bulan untuk
pasien yang diberikan kortikosteroid
• Survival 4 sampai 6 bulan untuk
pasien yang diberikan irradiasi
kranial

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TERIMA KASIH