Gen Pathology (Dra. Sionzon)

CNS PART 1 : CNS PATHOLOGY

16 February 2008

CNS PATHOLOGYCNS PATHOLOGY

Review: Principal cells of the CNSReview: Principal cells of the CNSNeuronsNeuronsGlial CellsGlial Cells

–– AstrocytesAstrocytes–– OlidodendrogliaOlidodendroglia–– ependymaependyma

MicrogliaMicrogliaMeningothelial cellsMeningothelial cells

Acute neuronal injuryAcute neuronal injury (red neurons): irreversible injury due (red neurons): irreversible injury due to various causes including hypoxia/ischemia, infections, toxinsto various causes including hypoxia/ischemia, infections, toxins

Chromatolysis: Chromatolysis: reaction w/in the neuronal cell body to axonalreaction w/in the neuronal cell body to axonal injuryinjury

Notes: Notes: negli bodies negli bodies – in rabies– in rabiescytopathic efeects cytopathic efeects – in CMV– in CMVneurofibrillary bundles – neurofibrillary bundles – in alzheimersin alzheimers

1.1. ASTROCYTESASTROCYTES star-shaped glial cellsstar-shaped glial cells functions include nutritional supply and insulation offunctions include nutritional supply and insulation of

neurons, contribution to blood brain barrierneurons, contribution to blood brain barrier play prominent role in response to injuryplay prominent role in response to injury cytoplasm of “resting” astrocytes not readily evident cytoplasm of “resting” astrocytes not readily evident response to tissue injury: hyperplasia and hypertrophy;response to tissue injury: hyperplasia and hypertrophy;

astrogliosisastrogliosis highlighted by immunostaining for GFAP highlighted by immunostaining for GFAP (Glial fibrillary(Glial fibrillary

Astrocytic protein –for astrocytic process)Astrocytic protein –for astrocytic process)

(a)(a) (b) (b)(a)(a) ASTROGLIOSIS (GLIOSIS)ASTROGLIOSIS (GLIOSIS)(b) GFAP STAINING OF REACTIVE ASTROCYTES(b) GFAP STAINING OF REACTIVE ASTROCYTES

2.2. OLIGODENDROCYTESOLIGODENDROCYTES Process wrap around axons of neurons to form myelin Process wrap around axons of neurons to form myelin Oligodendrocyte injury is a feature of demyelinatingOligodendrocyte injury is a feature of demyelinating

diseases (e.g multiple sclerosis)diseases (e.g multiple sclerosis) Nuclei may harbor viral inclusions in progressiveNuclei may harbor viral inclusions in progressive

multifocal leukoencephalopathymultifocal leukoencephalopathy Limited capacity for regenerationLimited capacity for regeneration

brim, leu, virns 1 of 10

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Notes: Notes: egg shaped dawegg shaped daw

3.3. EPENDYMAL CELLS EPENDYMAL CELLS Line ventricular chambers, aqueduct, central canal ofLine ventricular chambers, aqueduct, central canal of

spinal cordspinal cord Modulate the transfer of fluid between CSF andModulate the transfer of fluid between CSF and

parenchyma parenchyma Reaction to injury ; Reaction to injury ; ependymal granulationsependymal granulations (loss of (loss of

ependyma plus subependymal astrogliosis)ependyma plus subependymal astrogliosis)

FEATURES UNIQUE TO CNSFEATURES UNIQUE TO CNSEnclosed in a rigid bony compartmentEnclosed in a rigid bony compartmentAutoregulation of cerebral blood flowAutoregulation of cerebral blood flowDependent on glucose and high O2 supplyDependent on glucose and high O2 supplyCSF fills ventricles and spacesCSF fills ventricles and spacesLack a lymphatic circulationLack a lymphatic circulationCell have limited regenrative abilityCell have limited regenrative abilityImmunologically secludedImmunologically secludedBBB and blood CSF barrier separates the brain from BBB and blood CSF barrier separates the brain from the rest of the body the rest of the body

INTRACRANIAL COMPARTMENTSINTRACRANIAL COMPARTMENTSEpidural spaceEpidural spaceSubdural spaceSubdural space

Subarachnoid spaceSubarachnoid spaceCerebral parenchymal compartmentCerebral parenchymal compartmentIntravntricular spacesIntravntricular spaces

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PATHOLOGIC REACTIONSPATHOLOGIC REACTIONSSelective vulnerability”Selective vulnerability”Pathologic reactions of neuronsPathologic reactions of neurons

–– Acute injuryAcute injury–– DegenerationDegeneration–– Axonal reactionAxonal reaction–– Formation of neuronal inclusionsFormation of neuronal inclusions–– Vacuolization of cytoplasm and neurophilVacuolization of cytoplasm and neurophil–– Aggregation of abnormal proteinsAggregation of abnormal proteins–– NeuronophagiaNeuronophagia

Astrocytes - Gliosis – glial scarAstrocytes - Gliosis – glial scarMicroglia - glial nodulesMicroglia - glial nodules

–– Phagocytosis of dying neurons Phagocytosis of dying neurons (neuronophagia)(neuronophagia)

COMMON PATHOPHYSIOLOGIC PHENOMENA COMMON PATHOPHYSIOLOGIC PHENOMENA

A.A. CEREBRAL EDEMACEREBRAL EDEMA1.1. Vasogenic Edema Vasogenic Edema

–– blood brain barrier dysfunction, fluid blood brain barrier dysfunction, fluid accumulates between neurons and glial cellsaccumulates between neurons and glial cells

2.2. Cytotoxic Edema Cytotoxic Edema –– fluid accumulates inside the cells (ischemia, fluid accumulates inside the cells (ischemia,

hypoxia)hypoxia)3.3. Interstitial Edema Interstitial Edema

–– results from increase CSF (dysfunction of results from increase CSF (dysfunction of brain CSF barrier)brain CSF barrier)

–– Complication of hydrocephalusComplication of hydrocephalus

Gross Appearance Of The Brain In Vasogenic EdemaGross Appearance Of The Brain In Vasogenic EdemaCommon autopsy findingsCommon autopsy findings

–– Flattened broad gyriFlattened broad gyri–– Narrowed slit-like sulciNarrowed slit-like sulci–– Compressed lateral ventriclesCompressed lateral ventricles–– Brain is heavier than normal, soft; fluid seepsBrain is heavier than normal, soft; fluid seeps

from cut surfacesfrom cut surfaces–– Signs of herniation may be seenSigns of herniation may be seen

B.B. HERNIATIONSHERNIATIONS1.1. Cingulate Herniation/ SubfalcineCingulate Herniation/ Subfalcine

–– Cingulate gyrus compressed underneath the Cingulate gyrus compressed underneath the falx cerebrifalx cerebri

–– Caused by unilateral hemispheric massCaused by unilateral hemispheric mass2.2. Transtentorial Herniation/ UncinateTranstentorial Herniation/ Uncinate

–– Uncus gyri herniate in the cerebellar Uncus gyri herniate in the cerebellar tentoriumtentorium

3.3. Tonsillar HerniationTonsillar Herniation–– Cerebellar tonsils are compressed in the Cerebellar tonsils are compressed in the

foramen magnumforamen magnum–– Life threateningLife threatening

Brain surrounded by rigid skull Brain surrounded by rigid skull Rigid barriers divide the cranial cavity into Rigid barriers divide the cranial cavity into subcompartments (falx cerebri, cerebellar tentorium)subcompartments (falx cerebri, cerebellar tentorium)Intracranial volume is fixed (brain parenchyma, CSF, Intracranial volume is fixed (brain parenchyma, CSF, blood) blood) Space occupying masses (tumor, hemorrhage, etc), Space occupying masses (tumor, hemorrhage, etc), brain edema, increased CSFbrain edema, increased CSF lead to increased lead to increased intracranial pressure and may cause herniationintracranial pressure and may cause herniationHerniation is displacement of expanding brain to Herniation is displacement of expanding brain to adjacent subcompartments or through formaen adjacent subcompartments or through formaen magnummagnum

COMPLICATIONS OF BRAIN HERNIATIONCOMPLICATIONS OF BRAIN HERNIATIONNecrosisNecrosis of herniated parenchyma of herniated parenchymaCompression of vessels and consequent Compression of vessels and consequent infarctioninfarction (eg posterior cerebral artery infarction (eg posterior cerebral artery infarction involving the visual cortex)involving the visual cortex)Nerve compressionNerve compression (eg III cranial nerve in (eg III cranial nerve in transtentorial herniation w/ consequent papillary transtentorial herniation w/ consequent papillary dilation and impaired ocular movement)dilation and impaired ocular movement)Death Death (eg brainstem compression in tonsillar (eg brainstem compression in tonsillar herniationherniation

MALFORMATIONS AND DEVELOPMENTAL DEFECTSMALFORMATIONS AND DEVELOPMENTAL DEFECTS

A.A. DEVELOPMENTAL DISORDERSDEVELOPMENTAL DISORDERS1.1. Cranial DysraphismCranial Dysraphism

–– AnencephalyAnencephaly–– EncephaloceleEncephalocele

2.2. Spinal DysraphismSpinal Dysraphism–– Spina bifida occultaSpina bifida occulta–– MeningoceleMeningocele–– MeningimyeloceleMeningimyelocele–– Rachischisis Rachischisis

B.B. CNS MALFORMATIONS CNS MALFORMATIONS Congenital CNS MalformationCongenital CNS Malformation : Morphological CNS : Morphological CNS defect present at birth due to an abnormaldefect present at birth due to an abnormal development process)development process)Causes:Causes: unknown in a majority of cases, genetic and unknown in a majority of cases, genetic and chromosomal abnormalities, environmental (egchromosomal abnormalities, environmental (eg infection, drugd, nutritional, multifactorial)infection, drugd, nutritional, multifactorial)Anatomic pattern of malformation reflects the stage ofAnatomic pattern of malformation reflects the stage of formation of the CNS at the time of injuryformation of the CNS at the time of injury

Important types and examples:Important types and examples:1.1. Neural Tube DefectsNeural Tube Defects (eg anencephaly, (eg anencephaly,

myelomeningocele, spina bifida, encephalocele)myelomeningocele, spina bifida, encephalocele)2.2. Forebrain anomalies Forebrain anomalies (eg holoprosencephaly,(eg holoprosencephaly,

agenesis of the corpus callosum, neuronal migrationagenesis of the corpus callosum, neuronal migration defects, microencephaly)defects, microencephaly)

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3.3. Posterior fossa defects Posterior fossa defects (Arnold-Chiari and Dandy-(Arnold-Chiari and Dandy-Walker malformation)Walker malformation)

4.4. Hydromyelia, syringomyeliaHydromyelia, syringomyelia

1.1. NEURAL TUBE DEFECTSNEURAL TUBE DEFECTS Transformation of the neural plate into the neural tubeTransformation of the neural plate into the neural tube

occurs at 22-28 days of gestationoccurs at 22-28 days of gestation Neural tube defects are due to failure of a portion ofNeural tube defects are due to failure of a portion of

the neural tube to close or reopening of a region afterthe neural tube to close or reopening of a region after successful closuresuccessful closure

All characterized by abnormalities involving bothAll characterized by abnormalities involving both neural tissue and overlying one or soft tissuesneural tissue and overlying one or soft tissues

Most common type of CNS malformation, wideMost common type of CNS malformation, wide geographic and ethnic variation in frequency,geographic and ethnic variation in frequency, recurrence rate: 4-5%recurrence rate: 4-5%

Etiology: unknownEtiology: unknown, some association w/, some association w/ chromosomal disorders (trisomy 13), environmentalchromosomal disorders (trisomy 13), environmental factors (eg folate deficiency), interaction of geneticfactors (eg folate deficiency), interaction of genetic and environmental etiology suspected based onand environmental etiology suspected based on research in mice.research in mice.

Anenephaly with complete rachischisisAnenephaly with complete rachischisis (craniorachischisis) (craniorachischisis) : Skull vault and vertebral arches are deficient, replacement of: Skull vault and vertebral arches are deficient, replacement of

brain w/ vascular mass (area cerebrovasculosa)brain w/ vascular mass (area cerebrovasculosa)

Spinal neural tube defects:Spinal neural tube defects:Myelomeningocele:Myelomeningocele: herniation of the spinal cord and herniation of the spinal cord and meningeal tissue through a vertebral defect (picture)meningeal tissue through a vertebral defect (picture)Meningocele: Meningocele: herniation of meningeal tissue onlyherniation of meningeal tissue only

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Encephalocele (occipital) Encephalocele (occipital) : herniation of brain tissue through: herniation of brain tissue through a skull defecta skull defect2.2. FOREBRAIN ANOMALYFOREBRAIN ANOMALY

Forebrain anomaly: HoloprosencephalyForebrain anomaly: Holoprosencephaly Failure of separation of cerebral hemispheresFailure of separation of cerebral hemispheres May be associated with facial abnormalities (egMay be associated with facial abnormalities (eg

cyclopia)cyclopia) Etiology associations:Etiology associations:

oo trisomy 13, 18trisomy 13, 18oo Sonic hedgehog gene mutationsSonic hedgehog gene mutationsoo Maternal diabetes mellitusMaternal diabetes mellitusoo Toxoplasmosis, other infectionsToxoplasmosis, other infections

Forebrain anomaly: Agenesis of the corpus callosumForebrain anomaly: Agenesis of the corpus callosum Absence of white matter bundles connecting cerebralAbsence of white matter bundles connecting cerebral

hemisphereshemispheres

FOREBRAIN ANOMALYFOREBRAIN ANOMALY

AgyriaAgyria PolymicrogyriaPolymicrogyria

3.3. POSTERIOR FOSSA ABNORMALITY: Arnold- ChiariPOSTERIOR FOSSA ABNORMALITY: Arnold- Chiari Malformation (Chiari Type II Malformation)Malformation (Chiari Type II Malformation) Small posterior fossaSmall posterior fossa Downward extension of cerebellar vermis through Downward extension of cerebellar vermis through

foramen magnumforamen magnum Caudally displaced medulla Caudally displaced medulla Often associated;Often associated;

oo Aqueductal stenosisAqueductal stenosisoo HydrocephalusHydrocephalusoo Lumbar myelomeningoceleLumbar myelomeningoceleoo hydromyeliahydromyelia

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PERINATAL BRAIN INJURYPERINATAL BRAIN INJURY

Important cause of childhood neurological disabilityImportant cause of childhood neurological disability Cerebral PalsyCerebral Palsy (a clinical term): non-progressive (a clinical term): non-progressive

neurologic motor deficit attributable to insultsneurologic motor deficit attributable to insults occurring during the prenatal and perinatal periodoccurring during the prenatal and perinatal period

Most common underlying pathology : Most common underlying pathology : hemorrhageshemorrhages and infarctionsand infarctions

Premature infants at increased risk germinal matrixPremature infants at increased risk germinal matrix hemorrhage and periventricular infarcts leading tohemorrhage and periventricular infarcts leading to periventricular leucomalaciaperiventricular leucomalacia

In term infants: choroid plexus hemorrhage andIn term infants: choroid plexus hemorrhage and infarcts involving cerebral cortex, basal ganglia andinfarcts involving cerebral cortex, basal ganglia and thalamusthalamus

Common causes: maternal disease (eg hemorrhage,Common causes: maternal disease (eg hemorrhage, shock, drugs, trauma), placental abnormalities,shock, drugs, trauma), placental abnormalities, neonatal disease (eg congenital heart disease)neonatal disease (eg congenital heart disease)

GERMINAL MATRIX HEMORRHAGE GERMINAL MATRIX HEMORRHAGE in premature infantin premature infant

TRAUMATRAUMA

A.A. PHYSICAL INJURIESPHYSICAL INJURIESContusions (bruising)Contusions (bruising)

–– “Coup lesions” and “contre coup” contusion“Coup lesions” and “contre coup” contusion–– Rapid accelaration/ decelerationRapid accelaration/ deceleration

Laceration (tearing)Laceration (tearing)Diffuse Axonal InjuryDiffuse Axonal InjuryTraumatic vascular injuryTraumatic vascular injuryPenetrating woundsPenetrating wounds

B.B. SPINAL CORD INJURIESSPINAL CORD INJURIESHyperextension injuryHyperextension injury

–– Cervical spinalCervical spinal

–– Sudden posterior displacement of the head Sudden posterior displacement of the head –– Rupture of anterior spinal ligamentRupture of anterior spinal ligament

Hyperflexion injuryHyperflexion injury–– Impact force driving the head down andImpact force driving the head down and

forwardforward–– Anterior contusion of the cervical spineAnterior contusion of the cervical spine

C.C. INTRACRANIAL BLEEDINGINTRACRANIAL BLEEDINGEpidural hematomaEpidural hematomaSubdural hematomaSubdural hematomaSubarachnoid hematomaSubarachnoid hematomaIntracerebral hemorrhageIntracerebral hemorrhageIntraventricular hemorrhage “hydrocephalusIntraventricular hemorrhage “hydrocephalus internus”internus”

INFECTIONSINFECTIONS

A.A. CHRONIC BACTERIAL INFECTIONS - TUBERCULOSISCHRONIC BACTERIAL INFECTIONS - TUBERCULOSISManifestations: chronic mengitis and circumscribedManifestations: chronic mengitis and circumscribed abscess: abscess: TUBERCULOMATUBERCULOMATypically due to hematogenous spread of bacteriaTypically due to hematogenous spread of bacteria from pulmonary lesions or lymph nodesfrom pulmonary lesions or lymph nodesThis leads to This leads to caseous tuberclescaseous tubercles in the subarachnoid in the subarachnoid space or brain parenchymaspace or brain parenchyma

Caseous mycobacterial tubercles in the subarachnois spaceCaseous mycobacterial tubercles in the subarachnois space

Discharge of mycobacteria from tubercles into theDischarge of mycobacteria from tubercles into the subarachnoid space results in subarachnoid space results in tuberculous meningitistuberculous meningitis that that

typically affects the base of the brain.typically affects the base of the brain.

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Tuberculous meningitisTuberculous meningitis – microscopic findings: – microscopic findings: granulomatous inflammation w/ multinucleated giant cells,granulomatous inflammation w/ multinucleated giant cells,

epithelioid cells, macrophages and lymphocytes.epithelioid cells, macrophages and lymphocytes.

Tuberculoma: Tuberculoma: Growth or coalescence of small parenchymalGrowth or coalescence of small parenchymal tubercles creates abscesses w/ a caseous center. May occurtubercles creates abscesses w/ a caseous center. May occur

anywhere in the brain but show a predilection for theanywhere in the brain but show a predilection for the cerebellumcerebellum

B.B. CHRONIC BACTERIAL INFECTIONS -NEUROSYPHILISCHRONIC BACTERIAL INFECTIONS -NEUROSYPHILISNeurosyphylis Neurosyphylis is a tertiary stage of syphilis andis a tertiary stage of syphilis and occurs in about 10% of patients w/ untreated infectionoccurs in about 10% of patients w/ untreated infectionManifestations: meningeal- meningovascular syphilis,Manifestations: meningeal- meningovascular syphilis, paretic neurosyphilis, tabes dorsalisparetic neurosyphilis, tabes dorsalisMeningeal- Meningovascular SyphilisMeningeal- Meningovascular Syphilis : chronic : chronic mengitis w/ numerous plasma cellS that may bemengitis w/ numerous plasma cellS that may be associated w/ obliterative endarteritisassociated w/ obliterative endarteritisParetic NeurosyphilisParetic Neurosyphilis ; invasion of the brain by ; invasion of the brain by Treponema pallidum inflammatory meningeal lesionsTreponema pallidum inflammatory meningeal lesions are associated w/ parenchymal damage : loss ofare associated w/ parenchymal damage : loss of cortical neurons, striking proliferation of microglia (rodcortical neurons, striking proliferation of microglia (rod cells)cells)

Neurosyphilis : Neurosyphilis : leptomeningeal thickening, spirochetes andleptomeningeal thickening, spirochetes and rod cells. Patients show progressive loss of mental functions,rod cells. Patients show progressive loss of mental functions,

often often delusions of grandeur terminating in severedelusions of grandeur terminating in severe dementiadementia: general paresis of the insane: general paresis of the insane

Tabes dorsalis.Tabes dorsalis. Degeneration of the posterior columns of the Degeneration of the posterior columns of the spinal cord w/ loss of both axons and myelinspinal cord w/ loss of both axons and myelin

Symptoms:Symptoms: Impaired joint position sense, ataxiaImpaired joint position sense, ataxia Loss of pain sensation- skin and joint damageLoss of pain sensation- skin and joint damage Lightning painsLightning pains Loss of deep tendon reflexesLoss of deep tendon reflexes

C.C. VIRVIRAAL INFECTIONS ; VIRAL ASEPTIC MENINGITISL INFECTIONS ; VIRAL ASEPTIC MENINGITISMost common viral infection of the CNSMost common viral infection of the CNSCommon causative agents : Common causative agents : enteroviruses, herpesenteroviruses, herpes simplex virus type 2, mumps virussimplex virus type 2, mumps virusPathology : mild to moderate lymphocytic infiltrationPathology : mild to moderate lymphocytic infiltration of the leptomeningesof the leptomeningesClinical symptoms: headache, fever, usually short,Clinical symptoms: headache, fever, usually short, benign coursebenign course

D.D. VIRAL ENCEPHALITIS, MYELITIS, VIRAL ENCEPHALITIS, MYELITIS, ENCEPHALOMYELITISENCEPHALOMYELITIS

Viral infections of the brain (encephalitis), spinal cordViral infections of the brain (encephalitis), spinal cord (myelitis) or both (encephalomyelitis)(myelitis) or both (encephalomyelitis)Clinically most important infections caused by HIV,Clinically most important infections caused by HIV, Herpes Simplex Virus, Human Cytomegalovirus,Herpes Simplex Virus, Human Cytomegalovirus, Poliovirus, Rabies Virus, Measles Virus. JC Virus,Poliovirus, Rabies Virus, Measles Virus. JC Virus, ArbovirusesArbovirusesLocalization of the infection within the CNS is oftenLocalization of the infection within the CNS is often characteristic for specific virusescharacteristic for specific virusesMicroscopic pathology similar for almost all:Microscopic pathology similar for almost all: perivascular cuffs of the lymphocytes, astrogliosis,perivascular cuffs of the lymphocytes, astrogliosis,

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microglial nodules, if neurons are infected:microglial nodules, if neurons are infected: neuronophagianeuronophagiaViral inclusionsViral inclusions in some cases may be characteristic in some cases may be characteristic

E.E. HIV ENCEPHALITISHIV ENCEPHALITISAs many as 60% of patients w/ AIDS developAs many as 60% of patients w/ AIDS develop neurological dysfunctionneurological dysfunctionHIV infection can cause CNS damage by infecting theHIV infection can cause CNS damage by infecting the CNS and by leading to opportunistic CNS infectionsCNS and by leading to opportunistic CNS infectionsMain target cells of HIV in CNS : Main target cells of HIV in CNS : microglial cells andmicroglial cells and macrophagesmacrophagesCytokines and reactive oxygen and nitrogen speciesCytokines and reactive oxygen and nitrogen species released from infected cells may cause secondaryreleased from infected cells may cause secondary neuron damage and lead to HIV dementianeuron damage and lead to HIV dementiaTypically affects deep gray structures and whiteTypically affects deep gray structures and white mattermatterMultinucleated cells, microglial nodules, demyelinationMultinucleated cells, microglial nodules, demyelinationMost common opportunistic CNS infections in AIDS:Most common opportunistic CNS infections in AIDS: CMV Encephalitis, Toxoplasma Abscess, JC Virus –CMV Encephalitis, Toxoplasma Abscess, JC Virus – Induced Progressive Multifocal LeukoencephalopathyInduced Progressive Multifocal Leukoencephalopathy

F.F. HERPES SIMPLEX ENCEPHALITISHERPES SIMPLEX ENCEPHALITISMost common sporadic encephalitis in the US, affectsMost common sporadic encephalitis in the US, affects immunocompetent people, most commonly due toimmunocompetent people, most commonly due to HSV-1HSV-1Initial infection of mucocutaneous surfaces of oralInitial infection of mucocutaneous surfaces of oral cavity, nose, eyecavity, nose, eyeVirus infects nerve endings, reaches ganglia in theVirus infects nerve endings, reaches ganglia in the peripheral nervous system and the CNS by axonalperipheral nervous system and the CNS by axonal

transport = in most cases causes latent infection intransport = in most cases causes latent infection in neuronsneuronsInitial infection and reactivation from neurons mayInitial infection and reactivation from neurons may cause encephalitiscause encephalitisHSV encephalitis typically involves the HSV encephalitis typically involves the temporal lobetemporal lobe

G.G. CYTOMEGALOVIRUS INFECTION OF THE CNSCYTOMEGALOVIRUS INFECTION OF THE CNSCMV infection of the CNS occurs in two groups ofCMV infection of the CNS occurs in two groups of individuals : individuals : fetuses and the immunocompressedfetuses and the immunocompressedCongenital CMV infection l: the commonest of theCongenital CMV infection l: the commonest of the known intrauterine viral infections affecting 0.2-2.2%known intrauterine viral infections affecting 0.2-2.2% of live birthsof live birthsAcute infection: Acute infection: Necrotzing EncephalitisNecrotzing EncephalitisResidual lesions : microcephaly, polymicrogyria,Residual lesions : microcephaly, polymicrogyria, hydrocephalus and hydrocephalus and periventricular calcificationsperiventricular calcifications

Residual lesions of congenital CMV infection: periventricularResidual lesions of congenital CMV infection: periventricular calcifications and hydrocephaluscalcifications and hydrocephalus

CMV Ventriculoencephalitis in AIDSCMV Ventriculoencephalitis in AIDS: Virus targets: Virus targets ependyma and subependymal brain parenchyma. Noteependyma and subependymal brain parenchyma. Note

cytomegalic cells w/ intranuclear inclusionscytomegalic cells w/ intranuclear inclusionsH.H. FUNGAL INFECTIONS OF THE CNSFUNGAL INFECTIONS OF THE CNS

Affect primarily immunocompromised patients inAffect primarily immunocompromised patients in industrialized countriesindustrialized countries

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Often presents as a component of widespreadOften presents as a component of widespread hematogenous dissemination of fungushematogenous dissemination of fungusThree basic patterns : Three basic patterns : Vasculitis, ChronicVasculitis, Chronic Meningitis, And Parenchymal InvasionMeningitis, And Parenchymal Invasion (granulomas or abscesses)(granulomas or abscesses)Vasculitis commonly caused by Aspergillus and Mucor,Vasculitis commonly caused by Aspergillus and Mucor, occasionally Candidaoccasionally Candida

Mucormycosis:Mucormycosis: CNS vasculitis following local brain invasion CNS vasculitis following local brain invasion from a paranasal sinus in a diabetic patient w/ ketoacidosis.from a paranasal sinus in a diabetic patient w/ ketoacidosis.

ASPERGILLOSISASPERGILLOSIS

Candida Albicans InfectionCandida Albicans Infection most often associated with most often associated with microabscesses but may also cause vasculitis leading tomicroabscesses but may also cause vasculitis leading to

multiple hemorrhagic infarctsmultiple hemorrhagic infarcts

FUNGAL INFECTIONS FUNGAL INFECTIONS Fungi causing chronic mengitis:Fungi causing chronic mengitis: Histoplasma Histoplasma

capsulatum, Coccidioides immitis, Blastomyces capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Cryptococcus neoformansdermatitidis, Cryptococcus neoformans

Cryptococcal mengitisCryptococcal mengitis : observed in increased : observed in increased frequency in AIDS patientsfrequency in AIDS patients

Cryptococcus Meningitis: Cryptococcus Meningitis: multiple small cysts in the basalmultiple small cysts in the basal ganglia corresponding to aggregates of fungi within expandedganglia corresponding to aggregates of fungi within expanded perivascular (Virchow-robin) spaces with minimal associatedperivascular (Virchow-robin) spaces with minimal associated

inflammationinflammation

I.I. PROTOZOAL CNS INFECTION: TOXOPLASMOSISPROTOZOAL CNS INFECTION: TOXOPLASMOSISSimilarly to CMV, important cause of congenitalSimilarly to CMV, important cause of congenital infections and necrotizing encephalitis in theinfections and necrotizing encephalitis in the immunocompromisedimmunocompromisedCongenital toxoplasmaCongenital toxoplasma infection is responsible for infection is responsible for the classic triad of : the classic triad of : Chorioretinitis, CerebralChorioretinitis, Cerebral Calcifications And HydrocephalusCalcifications And HydrocephalusIn immunocompromised patients toxoplasma causesIn immunocompromised patients toxoplasma causes solitary or multifocal abscessessolitary or multifocal abscessesUp to 30% of AIDS patients affectedUp to 30% of AIDS patients affected

TOXOPLASMOSISTOXOPLASMOSIS

DISEASE OF MYELINDISEASE OF MYELIN

Diseases in w/c myelin is lost selectively w/ relative Diseases in w/c myelin is lost selectively w/ relative preservation of other neural structures including preservation of other neural structures including axonsaxons

Two main categories:Two main categories:VIII 1.VIII 1. associated w/ abnormal myelin metabolism: associated w/ abnormal myelin metabolism: LeukodystrophiesLeukodystrophiesVIII 2.VIII 2. associated w/ loss of normal myelin : associated w/ loss of normal myelin : Demyelinating diseases most common : multiple Demyelinating diseases most common : multiple clerosisclerosis

LEUKODYSTROPHIES LEUKODYSTROPHIES : inherited diseases, typical : inherited diseases, typical onset in infancy to adolescence, diffuse white matter onset in infancy to adolescence, diffuse white matter involvement, relentless progressive courseinvolvement, relentless progressive course

MULTIPLE SCLEROSISMULTIPLE SCLEROSIS sporadic incidence, typical sporadic incidence, typical onset in 20’s and 30’s, multiple demyelinating foci at onset in 20’s and 30’s, multiple demyelinating foci at different times during disease course, waxing and different times during disease course, waxing and waning coursewaning course

MULTIPLE SCLEROSISMULTIPLE SCLEROSIS Clinical Clinical : distinct episodes of neurological deficits : distinct episodes of neurological deficits

attributable to white matter lesions “ separated in attributable to white matter lesions “ separated in time and space “, waxing and waning coursetime and space “, waxing and waning course

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

Gross pathologyGross pathology; multiple, well delineated, firm, ; multiple, well delineated, firm, gray lesions (plaques) in white matter, may focally gray lesions (plaques) in white matter, may focally extend into gray matterextend into gray matter

Microscopic pathologyMicroscopic pathology : well defined area of myelin : well defined area of myelin loss with relative preservation of axons, lymphocytic loss with relative preservation of axons, lymphocytic infiltrate, loss of oligodendrocytes, foamy infiltrate, loss of oligodendrocytes, foamy macrophages, astrogliosismacrophages, astrogliosis

Shadow plaqueShadow plaque : only partial loss of myelin : only partial loss of myelin

guys, di na ko gumawa ng low ink version ha. kasi sabi ni doc kelngan daw yung pictures.. so ayan. magsayang na tayo ng ink! wohoo!!!!... eto pla e yung ppt lang. I checked the buk, dami pla niang di diniscuss.. Mga impt notes lang to.. so kahit mganda tong trans pagkagawa ko, don’t rely on this..lam ko namang masisipag kayo e. may medstudent bang tamad?! Kung tamad ka edi sna wla ka na ditto.. diba?!.. in short, read your books.. haha! ;) –brim