NEURO-PSYCHIATRY MODULE:PATHOLOGY PERSPECTIVEHARTONO TJAHJADI, ESTI B SOETRISNO, RAHMIATIDEPARTEMENT OF PATHOLOGICAL ANATOMY FMUI

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PATHOLOGICAL BASIS OF NEUROLOGICAL SIGNS AND SYMPTOMS

Sign or symptomPathological basisSign or symptomPathological basisHeadacheAbnormal reflexesIntra cranial causeRaised intracrainal pressureExaggeratedCorticospinal tract lesionStretching or pressure on intracranial vesselsImpairedPeripheral neuropathy or cerebellar diseaseDistortion or inflammation of meningesMuscle deficitExtra cranial causeReferred from paranasal sinuses, cervical or temporomandibular joints, teeth, ears, etc.WastingLoss of trophic stimulus from lower motor neuronesNeck stiffnessIrritation or inflammation of meningesMyopathyComa or impaired consiousnessMetabolic, eg :WeaknessDisease directly or indirectly affecting function of:Hypoglycaemia, ketoacidosis, drug-induced, hepatic failure.Upper or lower motot neurones, neuromuscular conduction, muscle functionBrainstem lesions, e.g.:Sensory impairment and/or paraesthesiaeDisease directly or indirectly affecting function of:Infarction, haemorrhageCortical neurones, conrticospinal tracts, peripheral nervesCerebral hemisphere lesions, eg:Visual field defects or blindnessIntracerebral or extracerebral haemorrhage, infaction, iinfections, traumaDisease involving the eyes, optic nerves or visual cortex (e.g. cataracts, tumors intrinsic or extrinsic to optic neural pathways, ischaemia)DementiaLoss of functioning neurones due to ischaemia, toxic injury or neurodegerative diseaseTinnitus and/or deafnessImpared transmission of sound through external meatus (e.g. wax) or through middle ear ossicles, or disease affecting the organ of Corti or the auditory nerves.Epileptic fitsParoxysmal neuronal discharges, either idiopathic or emanating from focus of cortical disease or damage

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INTRODUCTIONCONGENITAL MALFORMATION

TRAUMATIC

NEURODEGENERATIVE DISORDERS

NEOPLASM / TUMOR OF CNS

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CONGENITAL BRAIN DEFECTSDysraphic defects of the neural tube

Hydrocephalus

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CONGENITAL CNS MALFORMATIONMorphological CNS defect present at birth due to an abnormal developmental processCauses: unknown in a majority of cases, genetic and chromosomal abnormalities, environmental (e.g. infection, drugs, nutritional), multifactorialAnatomic pattern of malformation reflects the stage of formation of the CNS at the time of injuryImportant types and examples:Dysraphic defect of the neural tube (e.g. anencephaly, encephalocele, myelomeningocele, spina bifida,) Forebrain anomalies (e.g. holoprosencephaly, agenesis of the corpus callosum, neuronal migration defects, microencephaly)Posterior fossa defects (Arnold-Chiari and Dandy-Walker malformation)Hydromyelia, syringomyelia

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DYSRAPHIC DEFECTS OF THE NEURAL TUBEThe dysraphic defects of neural tube reflect impaired closure of dorsal aspect of the vertebral column

Varying from mild anomalies (e.g. spina bifida occulta), to severe anomalies (e.g. anencephaly, myelomeningocele, rachischisis).

These variations can be grouped as:open if the overlying skin is not intact, pending leakage of cerebrospinal fluid, and occult if the defect is well covered with full thickness skin. The two groups call for quite different approaches.

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Development of neural tubeNeurulation : fundamental embryonic process that leads to the development of the neural tube, which is the precursor of the brain and spinal cord.2 distinct phase of neurulation:Primary neurulation (week 3-4) : formation of the brain and most of the spinal cord until the upper sacral level.Secondary neurulation (weeks 5-6) : creates the lowest portion of the spinal cord including most of the sacral and the coccygeal regions.

Open dysraphism Occult dysraphismMeningocele & Myelomeningocele Spina bifidaSacral dimple: dermal sinus track with spina bifidaFailure of primary neurulation leads to open dysraphism : poses an immediate threat of CSF leakage consequently meningitis after birth. Severity of the neurological deficit depends on the degree of malformation as well as the level of the defect - the higher the level the worse is the prognosis.

Neural placode is exposed.

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Neural Tube DefectsTransformation of the neural plate into the neural tube occurs at 22-28 days of gestationNeural tube defects are due to failure of a portion of the neural tube to close.All characterized by abnormalities involving both neural tissue and overlying bone or soft tissuesMost common type of CNS malformation, wide geographic and ethnic variation in frequency.Etiology: unknown, some association with chromosomal disorders (trisomy 13), environmental factors (e.g. folate deficiency), interaction of genetic and environmental factors suspected based on research in mice

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Normal neural tube development in utero

The first 2 months of embryogenesis can be divided into 23 stages.

Around day 18 at stage 8, the neural plate is formed, followed by neural folds and their subsequent fusion.

Neuropore closure is to follow and completed by stage 12 around day 28.

When caudal neuropore fails to close, open dysraphism ensues.

From then until day 56, secondary neurulation sets in forming the spinal cord distal to the second sacral vertebra. Defective secondary neurulation results in occult dysraphism in which the caudal part of the spinal cord remains connected with theepidermis by tissues of mesenchymal origin the ultimate cause for tethering later on in life.

Since defect occurs so early in pregnancy, folate supplement, proven to be effective in preventing neural tube defects, has to begiven in the anticipation of pregnancy *

Neural Tube DefectsSince defect occurs so early in pregnancy, folate supplement, proven to be effective in preventing neural tube defects, has to begiven in the anticipation of pregnancy

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AnencephalyGenetic factorFailure of closure of the anterior neuroporeCommon malformationFrog-like faciesArea cerebrovasculosaUnderdeveloped hypothalamusAdrenal cortical hyperplasiaMultifactorial-Folic acid supplementation2/3 died in utero; 1/3 die 1 week post natal

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AnencephalyFailure of the neural tube to close results in the lack of closure of the overlying bony structures of the cranium and an absence of the calvarium, skin, and subcutaneous tissues of this region. The exposed brain is incompletely formed or even entirely absent. In most cases, the base of the skull contains only fragments of neural and ependymal tissue and residues of the meninges. Acrania (complete or partial absence of the cranium) results from an injury to the fetus between the 23rd and 26th days of gestation

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MyelomeningoceleHerniation of malformed cord + meninges through vertebral defectUsually associated with Arnold-Chiari and hydrocephalusLumbosacral level most common

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HYDROCEPHALUSDilatation of the cerebral ventricles.

It is not a malformation, but a deformation due to increased pressure in the ventricle.

Causes :Congenital :ObstructionDefective filtrationAcquiredDue to loss of brain tissue

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HYDROCEPHALUSHydrocephalus: Accumulation of excessive cerebrospinal fluid (CSF) within the ventricular system of the brainNormal CFS circulation: Produced by choroid plexus. From lateral ventricles, CSF enters the 3rd ventricle through Foramina Monro,and then flows into the 4th ventricle through the aqueduct. It exits through foramina Luschka and Magendi and then flows through subarachnoid space, arachnoid granulations which is absorbed into venous circulationCauses of hydrocephalus:Primary :

Increased CSF production (e.g. choroid plexus tumors)Obstruction of CSF flow (non-communicating hydrocephalus, e.g. aqueduct destruction by viral infection)Decreased CSF resorption (e.g. due to meningitis)Secondary :

Brain atrophy and compensatory ventricular dilatation (hydrocephalus ex vacuo, e.g. Alzheimers disease)

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Site of obstruction in the cerebrospinal fluid (CSF) pathway.Subarachnoid spaceArachnoid granulationChoroid plexusLateral ventricle3rd ventricleCerebral aqueduct4th ventricleExit foramina L & M

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End of first section

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TRAUMAAccidents are the leading cause of death in people under the age of 454th most common cause of death for the population in industrial countriesPhysical forces can cause four types of head injury: Scalp contusions and lacerations : clinically least significantSkull fractures, can be complicated by CSF leaks, meningitis, displaced bone fragments, cranial nerve palsiesVascular injury, : epidural, subdural, subarachnoid hematomasIntracerebral / parenchymal brain injury : contusion, laceration, diffuse axonal injuryType of injury depends on: shape of object causing trauma : blunt, sharp, bullet wound. force of impact : whether head is in motion or fixed, direction (coup or countracoup).Injury can be classified as open or closedConcussion: clinical syndrome of transient alteration of consciousness secondary to brain trauma (no structural damage)

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Vascular InjuryEPIDURAL HEMATOMA

SUBDURAL HEMATOMA

SUBARACHNOID HAEMORRHAGE

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Epidural HematomaArterial laceration, usually middle meningeal artery: rapid accumulation of bloodTemporal TraumaPossible lucid interval : 4-8 h no symptomHematoma 30-50 ml : SOL-like symptomHematoma increases,

intracranial > venous pressureVenous sinus compressed: ischemicCushing reflex : bradycardia occurring as a reflex initiated by physiologic response to increased intracranial pressure, usually seen in the terminal stages of acute head injury and may indicate imminent herniationAlways associated with a skull fracture, except in small childrenNeurosurgical emergency requiring evacuation or herniation and death will ensue

Cushing reflex : bradycardia occurring as a reflex initiated by physiologic response to increased intracranial pressure. The Cushing reflex is usually seen in the terminal stages of acute head injury and may indicate imminent herniation.When MAP (Mean Arterial Pressure) is less than ICP (Intracranial Pressure), the hypothalamus increases sympathetic stimulation of the heart, resulting in vasoconstriction, increased contractility, and increased cardiac output. The increase in blood pressure is detected by baroreceptors in the carotid arteries, triggering a parasympathetic response via vagal stimulation and inducing bradycardia. Bradycardia may also be stimulated by impinging on the vagal nerve due to increased intracranial pressure causing a stimulate parasympathetic response. An irregular respiratory pattern is typically the result of increased pressure on the brainstem due to swelling, or from a brainstem herniation.*

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Subdural Hematoma

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Subdural HematomaInflammation reactionLead into membraneAbsorbed completelyStatic Enlarged

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Subarachnoid Haemorrhage1/3 caused by accident2/3 rupture aneurysm

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Intracerebral / Parenchymal Brain InjuryTransient loss of consciousness due to trauma, no structural damage. Consciousness depends on the function of specific neurons, especially in the brainstem reticular formation. Concussion is exemplified in the boxing ring, these motions impact a quick torque on the brainstem and cause functional paralysis of the neurons of the reticular formation. Blow to the temporalparietal area may lead to a skull fracture but does not always cause a concussion

BruisedGreater force may lead to deathPermanent, may cause sequelePhagocytosis activated

CONCUSSIONCONTUSION

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Traumatic Parenchymal Brain Injury

Contusion: usually wedge-shaped lesion associated with edema, hemorrhage and necrosisBlunt trauma to immobile head = contusion of underlying brain (coup contusion)Mobile head impacts fixed mass = contusion of underlying brain and brain parenchyma opposite to site of impact (coup and contracoup contusions)Rotating head impacts fixed mass = diffuse axonal injury (white matter shearing, axonal spheroids, coma)

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CONTUSION BASE ON FORCE OF IMPACT

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BLAST EFFECT OF BULLET WOUND

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SPINAL INJURY

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End of second section

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NEURODEGENERATIVE DISORDERSCharacterized by progressive dysfunction and death of neurons. In these diseases neuronal loss is selective, affecting one or more groups of neurons while leaving others intact. As the most common neurodegenerative diseases primarily affect the elderly, this group of diseases is becoming increasingly significant with the progressive aging of the population in industrialized societies.

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TYPES OF NEURODEGENERATIVE DISORDERSCognitive disturbance (dementia)Degeneration involving cerebral cortex. Dementia. (e.g. Alzheimer disease, Pick disease)Movement disordersDegeneration of motor neurons. Motor weakness. (e.g. amyotrophic lateral sclerosis, spinal muscular atrophy)Degeneration involving the cerebellum and its connecting tracts (spinocerebellar degeneration). Cerebellar ataxia. (e.g. Friedreich ataxia, ataxia-telangiectasia)Degeneration involving substantia nigra and basal ganglia. Extrapyramidal defects: akinetic and rigid. (e.g. Parkinson disease, progressive supranuclear palsy,)Degeneration involving basal ganglia. Dysregulation of movement: hyperkinetic. (e.g. Huntington disease)Multiple system atrophy. May manifest as striatonigral degeneration, as (olivopontocerebellar atrophy), or as autonomic system dysfunction (Shy-Drager syndrome) or with overlapping symptoms of the above

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Focus on neurodegenerative disordersCognitive disturbance (dementia)Degeneration involving cerebral cortex. Dementia.

e.g. Alzheimer disease & Pick diseaseMovement disordersDegeneration involving substantia nigra and basal ganglia. Extrapyramidal defects: akinetic and rigid. e.g. Parkinson diseaseDemyelinating disorder : Leukodistropies and Multiple SclerosisToxic substance : Alcoholism

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ALZHEIMER DISEASEMost common cause of dementia accounting for more than half of the cases (second most common cause: vascular disease)Dementia: Impairment of previously attained occupational or social functioning due to persistent impairment of memory associated with an impaired intellectual function in one or more of the following domains: language, visuospatial skills, emotion, personality, cognition in the presence of normal consciousness.Alzheimer disease: Progressive course over 5-10 years; patients become immobile and muteThree main groups, with different molecular genetic associations:sporadic (commonest, ~90%): increased risk for Apo E4 carriersfamilial: mutations of amyloid precursor protein (APP, chr. 21), presenilin-2 (APP processing protein on chr.1), presenilin-1 (APP processing protein on chr.14)associated with Down syndrome: trisomy 21Risk factors: aging, head trauma, menopause, low educational levelProtective factors: anti-inflammatory and antioxidant drugs, estrogen, high educational level

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ALZHEIMER DISEASEInsidious and progressive neurologic disorder characterized :

Clinically by:loss of memory (eventual dementia), cognitive impairment Pathologically by : A-containing senile plaques and neurofibrillary tangles formed by tau filaments

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ALZHEIMER DISEASEGross: Cortical atrophy involving primarily the frontal, temporal, parietal lobes and the hippocampus;

Dilatation of the lateral ventricles

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ALZHEIMER DISEASEKey microscopic findings:- neuronal loss and gliosis- neuritic plaques- neurofibrillary tanglesPlaques and tangles can also be seen in the absence of dementia. The diagnosis of Alzheimer disease is based on neuritic plaque numbers significantly increased for age and clinical history of dementia.

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Cerebral amyloid angiopathy. A section of cerebral cortex from a patient with Alzheimer disease demonstrates vascular deposition of amyloid (hematoxylin and eosin).

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A neuron exhibits a basophilic, cytoplasmic neurofibrillary tangle. A silver stain illustrates the intracellular structure of a neurofibrillary tangle.

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PICK DISEASELobar sclerosisLoss of executive function followed by a dementia that can be indistinguishable from Alzheimer disease. Prototypical of frontotemporal dementias,SporadicSporadic Pick disease becomes symptomatic in mid-adult life and progresses relentlessly to death over a period of 3 to 10 years.

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Pick disease

The brain demonstrates severe atrophy of the frontal lobe and the superior temporal lobe gyrus.

A microscopic section of a large basophilic Pick body just below the nucleus.

Silver impregnation strongly stains a Pick body.

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PICK DISEASE

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PARKINSON DISEASEParkinsonism: muscular rigidity, bradykinesia, resting tremor, expressionless countenance, emotional lability, and cognitive impairments, including dementia late in the disease courseCause :Most common cause: Idiopathic Parkinsons disease (IPD)Other causes include vascular disease damaging the substantia nigra, drug-induced parkinsonism, progressive supranuclear palsy, othersTypical onset of IPD: 6th-8th decadesSporadic worldwide incidence of 1/100 people over age 50 yearsIPD is inherited in some families as an autosomal dominant traitPathology findings : loss of neurons, primarily in the substantia nigra, accumulation of Lewy bodies, formed by filamentous -synuclein aggregates.

Environmental agents: there is similarity between IPD and the disorder produced by MTPT (a byproduct of illicit production of meperidine analogues)*

Parkinson disease, Gross : The affected substantia nigra (right) is pallor (depigmented), compared to a normal brain (left).

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PARKINSON DISEASEMicroscopic changes in the substantia nigra and locus ceruleus: Neuron loss Pigment (neuromelanin)-laden macrophages Gliosis Lewy bodies in neurons

Lewy bodies: appear to be involved in the removal of damaged cytoskeletal proteins; contain cytoskeletal proteins and proteins involved in their metabolism: alpha synuclein, ubiquitin, etc.

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DISEASES OF MYELIN

Diseases in which myelin is lost selectively with relative preservation of other neural structures including axonsTwo main categories:Associated with abnormal myelin metabolism: LeukodystrophiesAssociated with loss of normal myelin: Demyelinating diseases, most common: multiple sclerosisLeukodystrophies: inherited diseases, typical onset in infancy to adolescence, diffuse white matter involvement, relentless progressive courseMultiple sclerosis: sporadic incidence, typical onset in 20s and 30s, multiple demyelinating foci at different times during disease course, waxing and waning course

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Leukodystrophy:Inherited disturbances in formation and preservation of myelinMetachromasia leukodystrophy : arylsulfatase A deficiency, autosomal recessive inheritance, intra- and extracellular deposition of metachromatic sulfatidesKrabbe disease : galactocerebroside-beta-galactosidase deficiency, autosomal recessive inheritance, perivascular accumulation of macrophages (globoid cells) containing undigested galactocerebrosideAdrenoleukodystrophy : peroxisomal defect associated with inability to degrade very long chain fatty acids, X-linked recessive inheritance

A coronal section of the brain reveals conspicuous loss of myelin in the superior half of the white matter of the parietal lobe

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AdrenoleukodystrophyAdrenoleukodystrophy: peroxisomal defect associated with inability to degrade very long chain fatty acids, X-linked recessive inheritanceA coronal section of the brain discloses extensive degenerative changes throughout the white matter

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MULTIPLE SCLEROSISMultiple patches of demyelination throughout white matterSensory and motoricExacerbation and remmision

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MULTIPLE SCLEROSISPrevalence: 1:1000 in US; rare in tropics; individuals assume relative risk of the environment where they spent their first 15 years

Genetic influence: association with certain HLA antigens; 25% concordance in monozygotic twins

These suggest pathogenic role of a very common environmental agent (virus?) and genetic susceptibility. Myelin destruction is immune mediated.

Clinical: distinct episodes of neurological deficits attributable to white matter lesions separated in time and space, waxing and waning course

Common symptoms: Motoric : impaired vision, motor weakness, Sensory : paresthesias, ataxia, etc.

Pathology : Multiple patches of demyelination throughout white matter

Exacerbation and remmision

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MULTIPLE SCLEROSIS

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MULTIPLE SCLEROSISA. A coronal section of the brain demonstrates prominent demyelinated plaques (arrows).

B. A luxol fast blue stain demonstrates multiple small demyelinating plaques involving subcortical white matter.

Microscopic pathology:

well defined area of myelin loss with relative preservation of axons, lymphocytic infiltrate, loss of oligodendrocytes, foamy macrophages, astrogliosis

Shadow plaque: only partial loss of myelin

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TOXIC DISORDERS: ALCOHOLISMThe toxic CNS effects of chronic alcoholism may be either:direct effects of ethanol orsecondary nutritional effects (e.g. thiamine deficiency)Direct CNS effects: cortical (cerebral) atrophy and cerebellar degenerationCerebellar degeneration: atrophy and loss of granule cells predominantly in the anterior superior part of the vermisCerebellar dysfunction occurs in about 1% of chronic alcoholics: truncal ataxia, unsteady gait, nystagmus

Wernicke syndromeCentral pontine myelinolysis

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End of third section

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TUMORS OF THE CNSTumors of the nervous system are either primary or metastatic (approximately 50-50%). In children CNS tumors represent 20% of all cancers. Primary CNS tumors very rarely metastasize outside the CNS. At the same time it is estimated that nearly 25% of cancer patients develop CNS metastasis. The location of tumors in the CNS is a very important determinant of morbidity and mortality. The most common primary CNS tumors are astrocytomas.

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NeoplasmMalignant: locationIn children a majority of tumors (70%) are infratentorial (in the posterior fossa)In adults a majority of tumors (70%) are supraratentorialSymptom:Sensory/motoricSeizureIncreased intracranial pressure

SYMPTOMS OF INTRACRANIAL TUMORS: An infiltrative neoplasm that destroys functional neural tissue creates a neurologic deficit, which may be sensory or motor or both, depending on the function of the affected brain region. Cognitive functions are not infrequently impaired. Alternatively, a neoplasm that irritates a functional area may initiate an involuntary release of neuronal activity that manifests as seizures. These include (1) motor seizures, (2) subtle visual and olfactory seizures (uncinate fits), and (3) seizure disorders that stem from vegetative centers of the brain. Meningiomas and the well-differentiated gliomas, such as astrocytomas, oligodendrogliomas, and gangliomas, are most likely to be associated with seizures.The mass of a neoplasm, combined with edema or hydrocephalus, causes increased intracranial pressure, which leads to headaches and vomiting*

PRIMARY CNS TUMORSClassification according to their presumed cell of origin:Gliomas, that include:Astrocytomas: e.g. fibrillary (diffuse) astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, pilocytic astrocytomaOligodendrogliomas: oligodendroglioma, anaplastic oligodendrogliomaEpendymomas: ependymoma, anaplastic ependymomaNeuronal tumors: e.g. gangliocytoma, cerebral neuroblastomaPoorly differentiated (embryonal) tumors: e.g. MedulloblastomaMeningiomas: meningiomaNerve sheath tumors: schwannoma, neurofibromaAdenohypophyseal tumors: pituitary adenomaWHO system assigns histological grades to primary CNS neoplasms:

grades I to IV (grade IV most malignant)

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GLIOMASPrimary CNS tumors: Glial tumor : ~ 60% astrocytic, Non glial tumor :~ 17% meningeal, ~8% nerve sheath

AstrocytomasAstrocytoma FibrillaryAstrocytoma ProtoplasmicAstrocytoma GemistocyticAstrocytoma AnaplasticGlioblastoma multiformeOligodendrogliomaEpendymoma

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LOCATION OF CNS NEOPLASM

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ASTROCYTOMA

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Fibrillary astrocytoma.

Gemistocytic astrocytoma.

Pilocytic astrocytoma.

A. Fibrillary astrocytoma. The neoplastic astrocytes demonstrate characteristic fibrillary processes. B. Gemistocytic astrocytoma. Neoplastic astrocytes exhibit ample eosinophilic cytoplasm and eccentric nuclei. C. Pilocytic astrocytoma. A section of a cerebellar tumor reveals cystic areas containing neoplastic astrocytes against a fibrillary background.*

Glioblastoma

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Oligodendroglioma

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Ependymoma

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MENINGIOMA

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METASTATIC CNS TUMORS

Represent 50% of CNS tumors in hospital patients~ 25% of cancer patients develop CNS metLung, breast, melanoma primaries most commonChoriocarcinoma: rare tumor with high likelihood of metastasizing to the brainProstatic carcinoma: common tumor almost never metastasizing to the brainOvary, Hodgkins disease also very rarely metastasize to the CNSGray/white matter junction is the most common siteGross and microscopic demarcation from brain typicalOften multiple separate foci in CNS

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THANK YOU29 November 2010

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*The first 2 months of embryogenesis can be divided into 23 stages.

Around day 18 at stage 8, the neural plate is formed, followed by neural folds and their subsequent fusion.

Neuropore closure is to follow and completed by stage 12 around day 28.

When caudal neuropore fails to close, open dysraphism ensues.

From then until day 56, secondary neurulation sets in forming the spinal cord distal to the second sacral vertebra. Defective secondary neurulation results in occult dysraphism in which the caudal part of the spinal cord remains connected with theepidermis by tissues of mesenchymal origin the ultimate cause for tethering later on in life.

Since defect occurs so early in pregnancy, folate supplement, proven to be effective in preventing neural tube defects, has to begiven in the anticipation of pregnancy *

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*Cushing reflex : bradycardia occurring as a reflex initiated by physiologic response to increased intracranial pressure. The Cushing reflex is usually seen in the terminal stages of acute head injury and may indicate imminent herniation.When MAP (Mean Arterial Pressure) is less than ICP (Intracranial Pressure), the hypothalamus increases sympathetic stimulation of the heart, resulting in vasoconstriction, increased contractility, and increased cardiac output. The increase in blood pressure is detected by baroreceptors in the carotid arteries, triggering a parasympathetic response via vagal stimulation and inducing bradycardia. Bradycardia may also be stimulated by impinging on the vagal nerve due to increased intracranial pressure causing a stimulate parasympathetic response. An irregular respiratory pattern is typically the result of increased pressure on the brainstem due to swelling, or from a brainstem herniation.*

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*Environmental agents: there is similarity between IPD and the disorder produced by MTPT (a byproduct of illicit production of meperidine analogues)*

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*SYMPTOMS OF INTRACRANIAL TUMORS: An infiltrative neoplasm that destroys functional neural tissue creates a neurologic deficit, which may be sensory or motor or both, depending on the function of the affected brain region. Cognitive functions are not infrequently impaired. Alternatively, a neoplasm that irritates a functional area may initiate an involuntary release of neuronal activity that manifests as seizures. These include (1) motor seizures, (2) subtle visual and olfactory seizures (uncinate fits), and (3) seizure disorders that stem from vegetative centers of the brain. Meningiomas and the well-differentiated gliomas, such as astrocytomas, oligodendrogliomas, and gangliomas, are most likely to be associated with seizures.The mass of a neoplasm, combined with edema or hydrocephalus, causes increased intracranial pressure, which leads to headaches and vomiting*

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*A. Fibrillary astrocytoma. The neoplastic astrocytes demonstrate characteristic fibrillary processes. B. Gemistocytic astrocytoma. Neoplastic astrocytes exhibit ample eosinophilic cytoplasm and eccentric nuclei. C. Pilocytic astrocytoma. A section of a cerebellar tumor reveals cystic areas containing neoplastic astrocytes against a fibrillary background.*

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