NEURO-ONKOLOGI
Bagian/SMF Saraf
FK-UGM/RS Dr. Sardjito
Yogyakarta
TUMOR PRIMER
JARINGAN SARAF
Riki Sukiandra
Bagian Ilmu Penyakit Saraf
FK UGM/SMF Saraf RS Dr Sardjito
PENDAHULUAN
• Frekuensi tumor berbeda tgt jenisnya
• Ada predileksi ttt yang menimbulkan
sindrome ttt
• Pertumbuhan dan invasivitas
mempengaruhi penampilan klinis
PENDAHULUAN
• Tumor primer & sekunder (10%) banyak terjadi di dalam cavum
cranii (8%) dan canalis spinalis (2%)
• Insiden:
seluruh tumor → 46 per 100.000
tumor primer → 15 per 100.000
• Pada dewasa → Glioma, Meningioma, Metastase
→ 80-85% letaknya supratentorial
• Pada anak → Medulloblastoma, Astrocytoma cerebeler
→ 15-20% letaknya infratentorial
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.
Etiology and Risk Factors
• Genetic
– Familial
– Several inherited disease
• Environmental
– Irradiation
– Severe head trauma
– Chronic exposure of the petrochemicals
Pathophysiology
Localized Cerebral Oedema
• Venulae compression
• Protease released tumor
• Small fragment protease released
• Site: white matter
Cerebral Oedema
• Vasogenic
• Sitotoxic
• Interstitial
Brain Edema
Cytotoxic edema : BBB is closed, no protein extravasation, no
enhancement in CT, cell swell
Vasogenic edema : BBB is disrupted, leaks of protein, enhance in
imaging, cell are stable, extracellular space expands,
Interstitial
EDEMA OTAK (Padmosantjojo, 2000)
Vasogenik: Kerusakan vaskulatur endotel
kapiler, gangguan Tight Junctions,
permeabilitas naik
Sitotoksik: Intact Barier Edema, Gangguan
pompa Na-K-ATPase, Natrium intrasel naik
Interstisial: Transudasi
TIK Meningkat (Padmosantjojo, 2000)
Doktrin Monroe Kellie VKS:
V darah (150) + VLCS (150) + V otak (1200)
TIK meningkat bila tidak ada keseimbangan
Volume KS dengan wadahnya
BRAIN SWELLING
VASOGENIC OEDEMA
HYPODENSE SWELLING
DYSAUTOREGULATION
ISODENSE SWELLING
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
Mechanism
• 1. Space occupying lesion
• 2. Ventricle compression
• 3. Destruction
Mechanism of symptoms and signs
• Invasion, irritation, or replacement of normal tissue
– Probably accounts for a minority of symptoms
– Characteristic of low-grade infiltrating gliomas
• Tumor growth compresses normal tissues
– Shifts of normal brain structures
– Compression of blood vessels causes ischemia
• New vessels formed with no bloodbrain barrier
Symptoms and signs caused by brain tumors depend on
the location of the tumor and histopathology (rapidity of
growth) What are these signs and symptoms?
• Generalized — largely due to increased ICP
• Focal — result of compression and/or ischemia of normal brain
at the site of the tumor
• False localizing — neurologic abnormalities occurring at a
distant site from the tumor due to shifts of cerebral structures
Headache features suggestive of a space-
occupying lesion (Dodick, 1997)
•Subacute and progressive
•New onset in adult life (>40 yr of age)
•Association with any of the following:
Nausea/ vomiting
Nocturnal occurrence or morning awakening
Worsening by changes in posture
Confusion, seizures, or weakness
Any abnormal neurologic sign
Gejala Tumor otak (Crow, 2001)
Def.Neurologis
Def. Neurologis Nyerikepala
Nyeri kepala Kejang(15-
Kejang (15-
progresif(70%)
progresif (70%) (>50%)
(>50%) 20%)
20%)
--Destruksi
Destruksiatau
atau
Memburukdidi Gangguan
kompresilangsung
langsung Memburuk Gangguan
kompresi pagihari
hari eksitabilitasneural
neural
pagi eksitabilitas
--Kompresi
Kompresiakibat
akibat
massa,edema
massa, edema
--Invasi
Invasiatau
ataukompresi
kompresi
--TIK
TIKtinggi
tinggi
--Sekunder
Sekunderatau
atau
psikogenik
psikogenik
Gejala Klinik Tumor otak (DeAngelis, 2001)
- Contralateral limb weakness
- Contralateral sensory loss
- Demensia
- Disfasia
- Ggn mood
- Disleksia, disgrafia, diskalkulia
- Ggn perilaku
- Disorientasi spasial
- Inkontinensia
- disfungsi olfaktorius
- Disfungsi opticus
Hemianopsia
Homonim
Kontralateral
- Ggn bahasa Nistagmus
- Ggn memori Disartria
- Ggn mood - Ggn saraf kranial Ataksia
- Ggn perilaku - Ggn fx vital
- Hearing & vision
pathways (Wilkinson, 1997)
KARAKTERISTIK NYERI KEPALA SOP
1.Tidak terlokalisir dengan baik
2.Perjalanan penyakit subakut progresif
3.Intensitas sedang sampai berat
4.Resisten terhadap analgetik biasa
(Dodick, 1997)
KARAKTERISTIK NYERI KEPALA SOP
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)
(Greenberg, 2001)
NYERI KEPALA YG PERLU PERHATIAN
1. Perjalanan penyakit subakut progresif
2. Onset usia dewasa tua ( > 40 tahun )
3. NK disertai tanda-tanda:
- mual/muntah tanpa peny.sistemik
- memberat pada dini hari
- memberat dengan perubahan posisi
- disertai kejang, kelemahan, pe
kesadaran, tanda neurologis abnormal
(Dodick, 1997)
ETIOLOGIES OF TUMOR HEADACHE
1. Increased ICP
tumor mass effect, hydrocephalus, mass
effect from associated edema or
hemorrhage
2. Invasion or compression of pain sensitive
structures: dura, blood vessels, periosteum
3. Secondary to difficulty with vision
1. Diplopia
2. Difficulty focusing
4. psychogenic
(Greenberg, 2001)
STRUKTUR PEKA NYERI DI KEPALA
1. Sinus venosus dan cabang kortikalnya
2. Arteria besar di otak
3. Duramater yang melingkupi dasar anterior &
fossa posterior
4. N. craniales V, IX, X
5. Saraf spinal: n. cervical I, II, III
(Gilroy, 2000)
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)
Stroke-like presentation
1. Hemmorrhage into a tumor
2. Rapid cerebral oedem
Symptom and Sign of Brain Tumor Based on Its Location ( Flower, 2000)
Location Symptoms
Parasagittal Monoparesis of the contralateral leg
Subfrontal Change in mentation, apathy or disinhibited behavior, urinary incontinence
Olfactory Anosmia with possible ipsilateral optic atrophy and contralateral papilledema (this triad
groove termed Kennedy-Foster syndrome)
Cavernous Multiple cranial nerve deficits (II, III, IV, V, VI), leading to decreased vision and diplopia
sinus with associated facial numbness
Occipital
Contralateral hemianopsia
lobe
Location Symptoms
Cerebelloponti
Decreased hearing with possible facial weakness and facial numbness
ne angle
Spinal cord Localized spinal pain, Brown-Sequard (hemispinal cord) syndrome
Exophthalmos, monocular loss of vision or blindness, ipsilateraldilated pupil that does
Optic nerve not react to direct light stimulation but might contract on consensual light stimulation;
often, monocular optic nerve swelling with optociliary shunt vessels
Sphenoid wing Seizures; multiple cranial nerve palsies if the superior orbital fissure involved
May protrude within supratentorial and infratentorial compartments, producing
Tentorial
symptoms by compressing specific structures within these 2 compartments
Foramen
Paraparesis, sphincteric troubles, tongue atrophy associated with fasciculatio
magnum
Treatment
• Supportive
– Corticosteroid
– Anticonvulsant
• Definitive
– Surgery
– Radiation
– Radionecrosis
– Chemotherapy
Treatment method for Brain Tumor (Flower, 2000)
Corticosteroids –
These agents reduce edema around tumor, frequently leading to
symptomatic and objective improvement in symptoms
Dexamethasone (Decadron, Dexasone) -- Postulated
mechanisms of action of corticosteroids in brain tumors
Drug Name include reduction in vascular permeability, cytotoxic
effects on tumors, inhibition of tumor formation, and
decreased CSF production.
16 mg/d PO/IV divided q6h in significant peritumoral
Adult Dose edema; continue until patient shows improvement; taper
to discontinue or to minimum effective dose
Pediatric Dose 0.15 mg/kg/d PO/IV divided q6h
Documented hypersensitivity; active bacterial or fungal
Contraindications
infection; peptic ulcer disease; psychosis; hypertension
Estrogen antagonists –
Inhibit effects of estrogen by competitively binding to estrogen
receptor
Tamoxifen (Nolvadex) -- Competitively binds to estrogen
Drug Name receptor, producing a nuclear complex that decreases
DNA synthesis and inhibits estrogen effects.
Reports of tamoxifen in malignant meningiomas
recommend 40 mg/m2 PO bid for 4 d; then, 10 mg PO bid
Adult Dose
for 10 d (not a standard protocol but in the treatment of
meningiomas remains experimental)
Pediatric Dose Not established
Documented hypersensitivity; leukopenia,
thrombocytopenia, or on anticoagulant therapy (can
increase prothrombin time); women with dysmenorrhea,
Contraindications
cataracts secondary to risk of corneal and retinal damage;
hyperlipoproteinemia; menstrual irregularity;
thromboembolic disease; or visual disturbance
Progesterone antagonists –
RU-486 has been used experimentally in the treatment of this
medical condition
RU-486 -- Experimental antiprogesterone agent.
Used in patients with recurrent benign
Drug Name
meningiomas; in one study of 14 patients, tumor
regression was reported in 5 of 14 patients.
Adult Dose 200 mg PO bid
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Radiation Therapy
• Radiation is used when the entire primary tumor cannot be
surgically removed
• External bean irradiation, stereotactic radiosurgery, brachitherap
Therapeutic effects of radiotherapy (Wilson, 2001)
Radiation creates ionized oxygen species that react with cellular DNA.
Tumor cells have less ability than healthy cells for DNA repair.
Thus, between fractionation doses, healthy cells have a greater probability
than tumor cells of repairing themselves. With each subsequent mitosis, the
cumulative effects of unrepaired DNA result in apoptosis (cell death)
of these tumor cells
HOW ABOUT CHEMOTHERAPY ?
-Disappointing
- Some chemotherapeutic agents can weaken the blood-
brain barrier (BBB) transiently and allow CNS seeding.
-A number of commonly used chemotherapeutic agents do not
cross the BBB, thus leaving the brain as a safe haven for tumor growth.
(Tse, 2002)
Figure. Drawings providing an overview of the anterior cranial
fossa anatomy and the surgical approaches
Figure. Drawing demonstrating incisions for bifrontal craniotomy
Figure. Drawings. Left: Bifrontal craniotomy. Right:
Removal of the supraorbital bar. n = nerve
Figure. View following extensive transbasal approach. sup
= superior
