BRAIN TUMORBRAIN TUMOR

YUNELDI ANWARYUNELDI ANWAR

DEPARTMENT NEUROLOGY MEDICAL DEPARTMENT NEUROLOGY MEDICAL FACULTY UNIVERSITY OF NORTH FACULTY UNIVERSITY OF NORTH

SUMATERASUMATERA

INTRODUCTIONINTRODUCTION

•• BRAIN TUMOR BRAIN TUMOR �� INTRA KRANIAL, MED INTRA KRANIAL, MED

SPINALIS AND MENINGESSPINALIS AND MENINGES

•• TWO TYPE TWO TYPE �� PRIMER AND SECUNDERPRIMER AND SECUNDER•• TWO TYPE TWO TYPE �� PRIMER AND SECUNDERPRIMER AND SECUNDER

•• PRIMER TUMOR PRIMER TUMOR �� ASTROCYTE, ASTROCYTE,

OLIGODENDROCYTE, EPENDEMOCYTE, OLIGODENDROCYTE, EPENDEMOCYTE, ARACHNOID, NEUROBLAST AND ARACHNOID, NEUROBLAST AND MEDULLUBLASTMEDULLUBLAST

•• SEKUNDER TUMOR SEKUNDER TUMOR �� METASTATIK FROM METASTATIK FROM

LUNG, BREAST, COLON AND SKINLUNG, BREAST, COLON AND SKIN

ETIOLOGYETIOLOGY

•• GENETIC GENETIC �� GENE DEVIATIONGENE DEVIATION

•• CONGENGITAL CONGENGITAL �� TERATOMA, CHORDOMATERATOMA, CHORDOMA

•• AGE AGE �� PINEALOMA, MEDULLOBLASTOMA PINEALOMA, MEDULLOBLASTOMA •• AGE AGE �� PINEALOMA, MEDULLOBLASTOMA PINEALOMA, MEDULLOBLASTOMA

(< 20 yr). MENINGIOMA (> 50yr)(< 20 yr). MENINGIOMA (> 50yr)

•• CARSINOGEN CARSINOGEN �� HYDROCARBON, HYDROCARBON,

NITROSAMINNITROSAMIN

•• HEAD INYURY, INFECTION, TOKSIN, HEAD INYURY, INFECTION, TOKSIN, RADIATION, VIRUSRADIATION, VIRUS

Risk factors related to CNS tumorDefinitive

� ionizing radiation���� immune supression (HIV infection)

PossibleElectromagnetic field (high tension wires, cellular telepon)Diets (N-nitroso compounds, Aspartame)Diets (N-nitroso compounds, Aspartame)Occupation (petroleum industry, agricultural pesticides)Household chemicals (hairdyes and sprays, household

pesticides)Head injury Medication (vitamin)Infections (Cysticercosis, varicella zoster, SV 40

CONCEPT OF PATOGENESIS CONCEPT OF PATOGENESIS PRIMER TUMORPRIMER TUMOR

•• HISTOGENIC THEORY HISTOGENIC THEORY (Bayley &Cushing) (Bayley &Cushing) ��

EMBRIOLOGICAL OF NERVE CELL AND GLIAEMBRIOLOGICAL OF NERVE CELL AND GLIA

•• RECENT THEORY RECENT THEORY �� TUMOR ARISES FROM TUMOR ARISES FROM •• RECENT THEORY RECENT THEORY �� TUMOR ARISES FROM TUMOR ARISES FROM

TRANSFORMATION OF ASTROCYTE, TRANSFORMATION OF ASTROCYTE, OLIGODENDROCYTE, MICROGLIOCYTE, OLIGODENDROCYTE, MICROGLIOCYTE, EPENDYMOCYTE EPENDYMOCYTE �� NEOPLASM CELL NEOPLASM CELL ��

MULTIPLICATION AND DIFFRENTIATIONMULTIPLICATION AND DIFFRENTIATION

PATHOFISIOLOGYPATHOFISIOLOGY

•• NORMAL CAVUM CRANII CONSIST OFNORMAL CAVUM CRANII CONSIST OF

�� Brain tissue ( 1400 gr )Brain tissue ( 1400 gr )

�� Cerebro spinal fluid ( 75 cc )Cerebro spinal fluid ( 75 cc )

�� Blood ( 75 cc )Blood ( 75 cc )�� Blood ( 75 cc )Blood ( 75 cc )

these component any time these component any time �� stabilstabil

•• Brain tumor Brain tumor �� increase intracranial pressureincrease intracranial pressure

•• Brain tumor Brain tumor �� cerebral edema cerebral edema �� cerebral cerebral herniationherniation

NORMAL BRAIN

Cerebral herniation

A. Subfacial/cingulate hern

B. Uncal herniation

C. Transtentorial/central hern

D. External herniation

E. Tonsillar herniation

CLASSIFICATIONCLASSIFICATION•• HISTOPATOLOGICAL PATTERNHISTOPATOLOGICAL PATTERN�� Primary brain tumorPrimary brain tumor �� histologicalhistologicalbenign or malformativebenign or malformative �� meningiomameningioma

pituitary adenoma, acustic neuroma, pituitary adenoma, acustic neuroma, craniopharyngioma, pilocytic astrocytomacraniopharyngioma, pilocytic astrocytomacraniopharyngioma, pilocytic astrocytomacraniopharyngioma, pilocytic astrocytomahemangioblastomahemangioblastomahistological malignanthistological malignant �� glioma (anaplasglioma (anaplas

tic astrocytoma, glioblastoma multiform), tic astrocytoma, glioblastoma multiform), ependymoma, oligodendroglioma, medulloblastoependymoma, oligodendroglioma, medulloblastoma, pineal cell tumor, chroid plexus carcinoma ma, pineal cell tumor, chroid plexus carcinoma

MENINGIOMA

GLIOBLASTOMA

CLASSIFICATIONCLASSIFICATION CONTCONT

•• METASTATIC BRAINMETASTATIC BRAIN TUMORSTUMORS

�� BREASTBREAST

�� LUNGLUNG�� LUNGLUNG

�� GI TRACTGI TRACT

�� PROSTATPROSTAT

�� SKINSKIN

INTRA CRANIAL METASTASISINTRA CRANIAL METASTASIS

•• Brain parenchyma Brain parenchyma �� breast, lung, breast, lung,

melanomamelanoma

•• Pituitary gland Pituitary gland �� breast, melanoma, breast, melanoma, •• Pituitary gland Pituitary gland �� breast, melanoma, breast, melanoma,

germ cellgerm cell

•• Dural based Dural based �� lung, lung, prostatprostat, breast, breast

•• LeptomeningealLeptomeningeal disease disease �� breast, lungbreast, lung

SKULL METASTASISSKULL METASTASIS

•• Skull base Skull base �� breast, breast, prostatprostat, ,

osteosarcomaosteosarcoma of skull, head and neck of skull, head and neck cancercancer

•••• CalvariumCalvarium �� breast, breast, prostatprostat

SPINE METASTASISSPINE METASTASIS

•• Epidural Epidural �� lung, breast, lung, breast, prostatprostat, ,

neuroblastomaneuroblastoma, lymphoma. Leukemia, lymphoma. Leukemia

•• LeptomeningealLeptomeningeal �� breast, lungbreast, lung•• LeptomeningealLeptomeningeal �� breast, lungbreast, lung

•• IntramedullaryIntramedullary �� breast, colon, lung, breast, colon, lung,

prostatprostat

•• Brachial plexus Brachial plexus �� lung, breast, lymphomalung, breast, lymphoma

•• LumbosacralLumbosacral plexus plexus �� pelvic tumorpelvic tumor

CLASSIFICATION BASED ON CLASSIFICATION BASED ON TOPOGRAPHY (LOCATION)TOPOGRAPHY (LOCATION)

•• SUPRA TENTORIAL TUMORSSUPRA TENTORIAL TUMORS

�� Cerebral lobe and deep hemispheric Cerebral lobe and deep hemispheric ��

glioma, meningioma, metastatic tumorglioma, meningioma, metastatic tumorglioma, meningioma, metastatic tumorglioma, meningioma, metastatic tumor

�� Sella turcica tumor Sella turcica tumor �� pituitary tumor, pituitary tumor,

craniopharyngiomascraniopharyngiomas

•• INFRATENTORIAL TUMORINFRATENTORIAL TUMOR

•• MEDULLASPINALIS TUMORMEDULLASPINALIS TUMOR

INFRATENTORIAL TUMORSINFRATENTORIAL TUMORS

•• ADULTSADULTS

�� Cerebellopontine angel Cerebellopontine angel �� acoustic acoustic

schwannomaschwannoma

�� Others sites Others sites �� brainstem gliomas, metastase,brainstem gliomas, metastase,�� Others sites Others sites �� brainstem gliomas, metastase,brainstem gliomas, metastase,

hemangioblastoma, ependymomahemangioblastoma, ependymoma

•• CHILDRENSCHILDRENS

�� Midline tumors Midline tumors �� medulloblastomasmedulloblastomas

�� Cerebellar lobes Cerebellar lobes �� astrocytomasastrocytomas

MEDULLA SPINALIS TUMORSMEDULLA SPINALIS TUMORS

•• EKSTRA DURALEKSTRA DURAL �� Metastatic tumorMetastatic tumor

•• INTRA DURALINTRA DURAL

�������� Ekstra medullaEkstra medulla �� meningiomameningioma�������� Ekstra medullaEkstra medulla �� meningiomameningioma

�� neurofibromasneurofibromas

�� Intra medullaIntra medulla �� ependymomaependymoma

�� astrositomaastrositoma

SYMPTOMS AND SIGNSSYMPTOMS AND SIGNS

•• Generalized symptoms caused by raised Generalized symptoms caused by raised

intracranial pressureintracranial pressure

•• Focal symptoms caused by invasion, Focal symptoms caused by invasion, •• Focal symptoms caused by invasion, Focal symptoms caused by invasion, ischemia and compressionischemia and compression

•• False localizing symptoms caused by shifts False localizing symptoms caused by shifts of cerebral structuresof cerebral structures

GENERALIZED SYMPTOMS AND GENERALIZED SYMPTOMS AND SIGNSSIGNS

•• HEADACHE HEADACHE

•• VOMITINGVOMITING

•• DROWSINESS ( VERTIGO AND DIZZINESS)DROWSINESS ( VERTIGO AND DIZZINESS)•• DROWSINESS ( VERTIGO AND DIZZINESS)DROWSINESS ( VERTIGO AND DIZZINESS)

•• VISUAL OBSCURATIONVISUAL OBSCURATION

•• PERSONALITY CHANGEPERSONALITY CHANGE

•• CONFUSIONCONFUSION

•• PAPILEDEMAPAPILEDEMA

•• APATHYAPATHY

MECHANISM HEADACHE MECHANISM HEADACHE ASSOCIATED WITH BRAIN TUMORASSOCIATED WITH BRAIN TUMOR

1.Traction on venous sinuses1.Traction on venous sinuses

2.Traction on meningeal arteries2.Traction on meningeal arteries

3.Traction on large arteries at base of the 3.Traction on large arteries at base of the 3.Traction on large arteries at base of the 3.Traction on large arteries at base of the

brainbrain

4.Pressure on cranial and cervical pain sensi4.Pressure on cranial and cervical pain sensi

tive structuretive structure

5.Dilatation of intracranial arteries5.Dilatation of intracranial arteries

6.Inflamation of pain6.Inflamation of pain--sensitive structuressensitive structures

FOCAL SYMPTOMS AND SIGNSFOCAL SYMPTOMS AND SIGNS

•• FRONTAL LOBEFRONTAL LOBE

�� Generalized seizureGeneralized seizure

�� Focal motor seizure (contra lateral)Focal motor seizure (contra lateral)�� Focal motor seizure (contra lateral)Focal motor seizure (contra lateral)

�� Expressive aphasia (dominant size)Expressive aphasia (dominant size)

�� Behavioral changesBehavioral changes

�� DementiaDementia

�� Gait disorders, incotinenceGait disorders, incotinence

�� HemipareseHemiparese

Frontal lobe tumor

FOCAL SYMPTOMS & SIGNSFOCAL SYMPTOMS & SIGNS

•• BASAL GANGLIABASAL GANGLIA

�� Hemiparesis (contralateral)Hemiparesis (contralateral)

�� Movement disorders (rare)Movement disorders (rare)�� Movement disorders (rare)Movement disorders (rare)

•• PARIETAL LOBEPARIETAL LOBE

�� Receptive aphasia (dominant size)Receptive aphasia (dominant size)

�� Spatial disorientation (non dominant)Spatial disorientation (non dominant)

�� Cortical sensory dysfungtion (contralat)Cortical sensory dysfungtion (contralat)

��AgnosiasAgnosias

Metastase parietal lobe tumor

FOCAL SYMPTOMS & SIGNSFOCAL SYMPTOMS & SIGNS

•• OCCIPITAL LOBEOCCIPITAL LOBE�� Hemiparesis (contralateral)Hemiparesis (contralateral)�� Visual disturbanceVisual disturbance

•• TEMPORAL LOBETEMPORAL LOBE•• TEMPORAL LOBETEMPORAL LOBE�� Complex partial (psychomotor) seizuresComplex partial (psychomotor) seizures�� Generalized seizuresGeneralized seizures�� Behavioral changesBehavioral changes�� Olfactory and complex seizuresOlfactory and complex seizures�� Visual aurasVisual auras�� Visual field defectVisual field defect

Occipital lobe tumor

Temporal lobe tumor

FOCAL SYMPTOMS & SIGNSFOCAL SYMPTOMS & SIGNS

•• CORPUS COLLOSUMCORPUS COLLOSUM

�� Dementia (anterior)Dementia (anterior)

�� Behavioral changesBehavioral changes

�� Memory loss (posterior)Memory loss (posterior)�� Memory loss (posterior)Memory loss (posterior)

�� Asymptomatic (mid)Asymptomatic (mid)

•• THALAMUSTHALAMUS

�� Sensory loss (contralateral)Sensory loss (contralateral)

�� Behavioral changes (posterior)Behavioral changes (posterior)

�� Languange disorders (dominant size)Languange disorders (dominant size)

FOCAL SYMPTOMS & SIGNSFOCAL SYMPTOMS & SIGNS

•• MIDBRAINS/PINEALMIDBRAINS/PINEAL�������� Paresis of vertical eyemovementParesis of vertical eyemovement�� Pupillary abnormalitiesPupillary abnormalities�� Precocious puberity (boys)Precocious puberity (boys)�� Precocious puberity (boys)Precocious puberity (boys)

•• SELLA/OPTIC NERVE/PITUITARYSELLA/OPTIC NERVE/PITUITARY�������� EndocrinopathyEndocrinopathy�� Bitemporal hemianopiaBitemporal hemianopia�� Monocular visual defectMonocular visual defect�������� Opthalmoplegia (cavernous sinus)Opthalmoplegia (cavernous sinus)

Pineal tumor

Pituitary tumor

FOCAL SYMPYOMS & SIGNSFOCAL SYMPYOMS & SIGNS

•• PONS/MEDULLAPONS/MEDULLA

�� Cranial nerve dysfungtionCranial nerve dysfungtion

�� Ataxia, nystagmus, spasticityAtaxia, nystagmus, spasticity

�� Weakness, sensory lossWeakness, sensory loss

•••• CERBELLO PONTINE ANGLECERBELLO PONTINE ANGLE

�� Deafness (ipsilateral)Deafness (ipsilateral)

�� Loss of facial sensation (ipsilateral)Loss of facial sensation (ipsilateral)

�� Facial weakness (ipsilateral), ataxiaFacial weakness (ipsilateral), ataxia

•• CEREBELLUMCEREBELLUM

�� Ataxia (ipsilateral)Ataxia (ipsilateral)

�� NystagmusNystagmus

Cerebellum tumor

FALSE LOCALIZING SIGNSFALSE LOCALIZING SIGNS

•• CRANIAL NERVECRANIAL NERVE

�� AnosmiaAnosmia

�� Diplopia, ptosis, anisocoriaDiplopia, ptosis, anisocoria�� Diplopia, ptosis, anisocoriaDiplopia, ptosis, anisocoria

�� Face pain, numbness, and weaknessFace pain, numbness, and weakness

�� Tnnitus, hearing lossTnnitus, hearing loss

FALSE LOCALIZING SIGNSFALSE LOCALIZING SIGNS

•• PARENCHYMAL SIGNSPARENCHYMAL SIGNS

�� IpsilateralIpsilateral hemiparesishemiparesis

�� IpsilateralIpsilateral gaze palsygaze palsy�� IpsilateralIpsilateral gaze palsygaze palsy

�� Visual field defect, cortical blindnessVisual field defect, cortical blindness

�� AtaxiaAtaxia

•• OTHER SIGNSOTHER SIGNS

�� NuchalNuchal rigidityrigidity

SYMPTOM AND SIGN SPINAL SYMPTOM AND SIGN SPINAL CORD TUMORCORD TUMOR

•• INTRAMEDULLARYINTRAMEDULLARY

�� Sensory lossSensory loss

�� Early Early spinchterspinchter dysfungtiondysfungtion�� Early Early spinchterspinchter dysfungtiondysfungtion

�� Pain +Pain +

�� Decreased rectal toneDecreased rectal tone

�� spasticityspasticity

�� upper motor neuron signsupper motor neuron signs

Common tumor Common tumor --> > EpendymomaEpendymoma, , astrositomaastrositoma

Symptom and signs spinal cord Symptom and signs spinal cord tumortumor

•• IntraduralIntradural and and extramedullaryextramedullary

�� Pain, Pain, metastasemetastase ++++++

�� Pain, primary tumor +Pain, primary tumor +�� Pain, primary tumor +Pain, primary tumor +

�� RadicularRadicular or local sensory lossor local sensory loss

�� RadicularRadicular or segmental weakness and or segmental weakness and

sensory losssensory loss

�� Upper motor neuron signsUpper motor neuron signs

Common tumors Common tumors �� MeningiomaMeningioma

Symptom and sign spinal cord Symptom and sign spinal cord tumortumor

•• EPIDURALEPIDURAL

�� Pain +++Pain +++

�� RadicularRadicular or local painor local pain�� RadicularRadicular or local painor local pain

Common tumors Common tumors �� MetastasisMetastasis

DIAGNOSIS BRAIN TUMORDIAGNOSIS BRAIN TUMOR

•• HISTORYHISTORY

•• GENERAL PHYSICAL EXAMINATIONGENERAL PHYSICAL EXAMINATION

•• NEUROLOGIC EXAMINATIONNEUROLOGIC EXAMINATION•• NEUROLOGIC EXAMINATIONNEUROLOGIC EXAMINATION

•• LABORATORY FINDING, ESPECIALLY LABORATORY FINDING, ESPECIALLY IMAGINGIMAGING

Laboratory findingsLaboratory findings

•• IMAGINGIMAGING

�� CT ScanCT Scan

�� MRIMRI�� MRIMRI

�� Magnetic resonance spectroscopy (MRS)Magnetic resonance spectroscopy (MRS)

�� Fungtional MRIFungtional MRI

•• BIOPSYBIOPSY �� Defenitive diagnosisDefenitive diagnosis

DIFFRENTIAL DIAGNOSIS OF DIFFRENTIAL DIAGNOSIS OF BRAIN TUMORSBRAIN TUMORS

•• HEMATOMAHEMATOMA

•• ABCESSABCESS

•• GRANULOMAGRANULOMA•• GRANULOMAGRANULOMA

•• PARASITIC INFECTION PARASITIC INFECTION �� CYSTYCIRCOSISCYSTYCIRCOSIS

•• VASCULAR MALFORMATIONVASCULAR MALFORMATION

•• MULTIPLE SCLEROSISMULTIPLE SCLEROSIS

•• CEREBRAL INFARCSCEREBRAL INFARCS

Therapy of Intra Cranial TumorsTherapy of Intra Cranial Tumors

•• Definitive therapyDefinitive therapy

�� Surgery Surgery �� Biopsi, resectionBiopsi, resection

�� Radiation Radiation �� External beamExternal beam�� Radiation Radiation �� External beamExternal beam

�� Streotactic radiosurgeryStreotactic radiosurgery

�� Heavy particlesHeavy particles

�� BrachytherapyBrachytherapy

�� Chemotherapy Chemotherapy �� Parentral, lokalParentral, lokal

�� Experimental modalitiesExperimental modalities

•• Supportive therapySupportive therapy

Experimental modalitiesExperimental modalities

•• Angiogenesis inhibitorAngiogenesis inhibitor

•• Growth factor inhibitorGrowth factor inhibitor

•• Diffrentiating agentsDiffrentiating agents•• Diffrentiating agentsDiffrentiating agents

•• ImmunotherapyImmunotherapy

•• Gene therapyGene therapy

•• Antisense oligonucleotideAntisense oligonucleotide

Supportive TherapySupportive Therapy

•• AnticonvulsantAnticonvulsant

•• CorticosteroidsCorticosteroids

•• AntiAnti--thrombosis agentthrombosis agent•• AntiAnti--thrombosis agentthrombosis agent

•• Psychotropic agentsPsychotropic agents

•• Physical therapyPhysical therapy

Goals of SurgeryGoals of Surgery

•• Establish the diagnosisEstablish the diagnosis

•• Cure the patientCure the patient

•• Decrease tumor burdenDecrease tumor burden•• Decrease tumor burdenDecrease tumor burden

•• Relieve symptomsRelieve symptoms

•• Improve neurologic fungtionImprove neurologic fungtion

•• Extend duration and quality of liveExtend duration and quality of live

Basic concepts in cancer Basic concepts in cancer chemotherapychemotherapy

•• Chemotherapeutic agent kill only a Chemotherapeutic agent kill only a percentage of cancer cellpercentage of cancer cell

•• Some drugs kill only dividing cellsSome drugs kill only dividing cells•• Some drugs kill only dividing cellsSome drugs kill only dividing cells

•• Multiple drugs with differing site of action Multiple drugs with differing site of action are better than a single drugsare better than a single drugs

•• High dosee are better than low dosesHigh dosee are better than low doses

Brain tumors anticonvulsantBrain tumors anticonvulsant

•• ProphylaxisProphylaxis

---- does not prevent first seizuredoes not prevent first seizure

---- probably useful in perioperative periodprobably useful in perioperative period

••---- probably useful in perioperative periodprobably useful in perioperative period

•• TreatmentTreatment

---- efficacy unclearefficacy unclear

---- side effects more commonsside effects more commons

---- hard to control levelshard to control levels

---- best drug unknownbest drug unknown

Advantages and Disadvantages Advantages and Disadvantages of corticosteroidof corticosteroid

•• AdvantagesAdvantages

---- control neurologic symptom by reducecontrol neurologic symptom by reduce

edemaedemaedemaedema

---- decrease acute RT toxicitydecrease acute RT toxicity

---- relieve emesis from chemotherapyrelieve emesis from chemotherapy

---- oncolytic (lymphoma)oncolytic (lymphoma)

•• DisadvantagesDisadvantages

---- side effects commonside effects common

---- decrease chemotherapy entrydecrease chemotherapy entry