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Pathology of thePathology of the Nervous SystemNervous System

JANTIMA TANBOON,MDJANTIMA TANBOON,MD

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Central nervous systemCentral nervous systemPeripheral nervous systemPeripheral nervous system

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Normal cellsNormal cells

NeuronNeuron

GliaGlia

MacrogliaMacroglia: ectoderm: ectoderm

Microglia: mesodermMicroglia: mesoderm

Choroid plexusChoroid plexus

NeuropilNeuropil

MeningothelialMeningothelial cellscells Virchow-Robin space

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NeuronNeuron

Nuclei, ganglia Nuclei, ganglia

Cell body (Cell body (perikaryonperikaryon), processes), processes

Eccentric nucleusEccentric nucleus

Prominent nucleolusProminent nucleolus

Abundant Abundant NisslNissl substancesubstance

Microtubule, Microtubule, neurofilamentneurofilament, prominent , prominent golgigolgi, ,

rERrER, synaptic specialization, synaptic specialization

NFP, NFP, NeuNNeuN, , synaptophysinsynaptophysin27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 66

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GliaGlia

MacrogliaMacroglia <<-- neuroectodermneuroectoderm

Astrocytes,OligodendrocytesAstrocytes,Oligodendrocytes, , EpendymaEpendyma

MicrogliaMicroglia <<-- bone marrowbone marrow

Inflammation, repair, fluid balance, energy Inflammation, repair, fluid balance, energy

metabolismmetabolism

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AstrocytesAstrocytes

RoundRound--oval nucleioval nuclei

Pale chromatinPale chromatin

Gray/white matterGray/white matter

Protoplasmic: grayProtoplasmic: gray

Fibrous: gray/whiteFibrous: gray/white

Star shapeStar shape

GFAP, Golgi methodGFAP, Golgi method

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AstrocytesAstrocytes

ProcessesProcesses

NeuronNeuron

Metabolic buffersMetabolic buffers

DetoxifiersDetoxifiers

Nutrient suppliersNutrient suppliers

Electrical insulatorElectrical insulator

Capillaries Capillaries

Barriers: blood, CSF, brainBarriers: blood, CSF, brain

Repair, scar formation/ fibroblastRepair, scar formation/ fibroblast27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 1010

OligodendrocytesOligodendrocytesProcesssesProcessses wrap neural axons wrap neural axons Like Schwann cells in PNSLike Schwann cells in PNSMultiple internodesMultiple internodesSmall round lymphocyteSmall round lymphocyte--like nucleilike nucleiLinear arraysLinear arrays

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EpendymalEpendymal cellscells

Line ventricular systemLine ventricular system

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MicrogliaMicroglia

MesodermMesoderm-- bone marrowbone marrow

Macrophages of CNSMacrophages of CNS

Injury responseInjury response

1.1. ProliferationProliferation

2.2. Developing elongated (rod cells)Developing elongated (rod cells)-- syphillissyphillis

3.3. MicroglialMicroglial nodulesnodules

4.4. NeuronophagiaNeuronophagia

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Reaction of Reaction of neuronsneurons to injuryto injury

Acute neuronal change (red neuron)Acute neuronal change (red neuron)

SubacuteSubacute and chronic neuronal injury (degeneration)and chronic neuronal injury (degeneration)

Axonal reactionAxonal reaction

SubcellularSubcellular alteration in organelles and alteration in organelles and cytoskeletalcytoskeletal

Neurodegenerative changesNeurodegenerative changes

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Acute neuronal change (Acute neuronal change (red neuronred neuron))

Acute CNS hypoxic/ Acute CNS hypoxic/

ischemicischemic

H+E 12H+E 12--24 hrs24 hrs

Shrinkage cell bodyShrinkage cell body

Nuclear Nuclear pyknosispyknosis

Loss of nucleolusLoss of nucleolus

Loss of Loss of NisslNissl substancesubstance

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SubacuteSubacute and chronic neuronal injury and chronic neuronal injury (degeneration)(degeneration)Cell lossCell lossReactive Reactive gliosisgliosis (early detect)(early detect)

Axonal reactionAxonal reaction

Regeneration of axonRegeneration of axon-->>Axonal spheroidsAxonal spheroids

Increase protein synthesisIncrease protein synthesis--> sprouting> sprouting

Enlarge, round up cell bodyEnlarge, round up cell body

Peripheral nuclear displacementPeripheral nuclear displacement

Dispersion of Dispersion of NisslNissl substance to peripherysubstance to periphery

Central Central chromatolysischromatolysis27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 2020

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SubcellularSubcellular alteration in organelles and alteration in organelles and cytoskeletalcytoskeletal

LipofuscinLipofuscin, proteins, CHO, proteins, CHOViral inclusionViral inclusion

IntranuclearIntranuclearIntracytoplasmicIntracytoplasmic

Neurodegenerative changesNeurofibrillaryNeurofibrillary tanglestangles--AlzheimerAlzheimer

LewyLewy bodybody-- ParkinsonParkinson

Abnormal Abnormal vacuolationvacuolation-- CJDCJD27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 2222

Reaction of Reaction of AstrocytesAstrocytes to injuryto injury

GliosisGliosis******--indicator of CNS injuryindicator of CNS injury

Cellular swellingCellular swelling

Rosenthal fibersRosenthal fibers

Corpora Corpora amylaceaamylacea

GlialGlial cytoplasmiccytoplasmic inclusioninclusion

Alzheimer type II Alzheimer type II astrocyteastrocyte

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GliosisGliosis

AstrocyteAstrocyte: hypertrophy hyperplasia: hypertrophy hyperplasia

Nucleus: eccentric, enlarged vesicular, Nucleus: eccentric, enlarged vesicular,

prominent nucleolusprominent nucleolus

ScantScant-->bright pink cytoplasm>bright pink cytoplasm

GemistocyticGemistocytic astrocyteastrocyte

GlialGlial fibrilsfibrils

Bergmann Bergmann gliosisgliosis

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Rosenthal fibersRosenthal fibers

Thick elongated brightly Thick elongated brightly eosinophiliceosinophilic

Irregular contour within Irregular contour within astrocyticastrocytic processprocess

Long standing Long standing gliosisgliosis

PilocyticPilocytic astrocytomaastrocytoma

CraniopharyngiomaCraniopharyngioma

SyrinxSyrinx cavitiescavities

Alexander diseaseAlexander disease

ααBB--crystallincrystallin, hsp27, , hsp27, ubiquitinubiquitin

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Corpora Corpora amylaceaamylacea

Concentrically Concentrically lamellatedlamellated round faintly basophilic, round faintly basophilic, PAS positive 5PAS positive 5--5050µµmm

Heat shock protein, Heat shock protein, ubiquitinubiquitin

AstrocyticAstrocytic end processend process

SubpialSubpial

PerivascularPerivascular zonezone

Advance ageAdvance age

Adult Adult polyglucosanpolyglucosan bodybody

LaforaLafora bodybody (cytoplasm)(cytoplasm)

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Alzheimer type II Alzheimer type II astrocyteastrocyte

Gray matterGray matter

Nucleus 2Nucleus 2--3 times> normal3 times> normal

Pale staining central chromatinPale staining central chromatin

UnrelatedUnrelated to Alzheimer diseaseto Alzheimer disease

HyperamonemiaHyperamonemia

Chronic liver diseaseChronic liver disease

Wilson diseaseWilson disease

Hereditary disorder of Urea cycleHereditary disorder of Urea cycle

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Cerebral edemaCerebral edemaVasogenicVasogenic edemaedema

Disrupted normal BBBDisrupted normal BBBvascular permeabilityvascular permeability

Intercellular spaceIntercellular spaceLocalized/generalizedLocalized/generalized

CytotoxicCytotoxic edemaedemaNeuronal/Neuronal/glialglial/endothelial injury/endothelial injuryIntracellularIntracellularGeneralized hypoxic/ischemicGeneralized hypoxic/ischemic

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Increase intracranial pressureIncrease intracranial pressure

HerniationHerniationSubfalcineSubfalcine ((cingulatecingulate))

TranstentorialTranstentorial

((uncinateuncinate, , mesialmesial temporal)temporal)

TonsillarTonsillar herniationherniation

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SubfalcineSubfalcine ((cingulate)herniationcingulate)herniation

ACA compromisedACA compromised

TonsillarTonsillar herniationherniation

LifeLife--threateningthreatening

Brain stem compressionBrain stem compression

Respiratory and cardiac center in medullaRespiratory and cardiac center in medulla

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TranstentorialTranstentorial((uncinateuncinate, , mesialmesial temporal)temporal) herniationherniation

CNIII compressed CNIII compressed --> pupil dilate> pupil dilate

Impair Impair ipsilateralipsilateral ocular movementocular movement

PCA compressedPCA compressed-->primary visual cortex>primary visual cortex

ContralateralContralateral peduncle compresspeduncle compress

KernohanKernohan’’ss notchnotch

IpsilateralIpsilateral hemiparesishemiparesis

Hemorrhage in midbrain, Hemorrhage in midbrain, ponspons

Secondary brain stem (Secondary brain stem (DuretDuret hemorrhagehemorrhage))27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 3434

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CSFCSFProduced: Choroid plexusProduced: Choroid plexusAbsorbed: Absorbed: ArachnoidArachnoid granulationgranulation

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HydrocephalusHydrocephalus

Accumulation of excessive CSF Accumulation of excessive CSF

Impaired flowImpaired flow

Impaired absorptionImpaired absorption

OverproductionOverproduction

Hydrocephalus ex Hydrocephalus ex vacuovacuo

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NoncommunicatingNoncommunicating hydrocephalushydrocephalusCongenital malformationCongenital malformation

Tumor Tumor

Inflammation Inflammation

HemorrhageHemorrhage

Communicating hydrocephalusCommunicating hydrocephalusSubarachnoid hemorrhageSubarachnoid hemorrhage

MeningitisMeningitis

Metastasis to subarachnoid space Metastasis to subarachnoid space 27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 3838

Neural tube defectsNeural tube defects

1.1. AnencephalyAnencephaly

2.2. EncephaloceleEncephalocele

3.3. SpinaSpina bifidabifida**(spinal (spinal dysraphismdysraphism))

4.4. MyelomeningoceleMyelomeningocele

Maternal blood: Maternal blood: AFP, AFP, acetylcholinesteraseacetylcholinesterase

FolateFolate deficiencydeficiency

Subsequent pregnancy 4Subsequent pregnancy 4--5%5%

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Forebrain anomalyForebrain anomaly

1.1. PolymicrogyriaPolymicrogyria

2.2. MegalencephalyMegalencephaly

3.3. MicroencephalyMicroencephaly**

4.4. LissencephalyLissencephaly

5.5. Neuronal Neuronal heterotopiaheterotopia

6.6. HoloprocencephalyHoloprocencephaly

7.7. Agenesis of corpus Agenesis of corpus callosumcallosum

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Posterior Posterior fossafossa anomalyanomaly

ArnoldArnold--ChiariChiari malformationmalformationType I: less severe, tonsilsType I: less severe, tonsilsType II: Type II: vermisvermisSmall posterior Small posterior fossafossa, large foramen magnum, , large foramen magnum, low insertion of tentlow insertion of tentcaudal displacement of medulla, caudal displacement of medulla, tectumtectummalformation, aqueduct malformation, aqueduct stenosisstenosis, , cerebralheterotopiacerebralheterotopia, , hydromyelialhydromyelial

DandyDandy--Walker malformationWalker malformation

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Type I Type II

Arnold- Chiari malformation

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DandyDandy--Walker malformationWalker malformation

Enlarged posterior Enlarged posterior fossafossa, , Agenesis of Agenesis of vermisvermis, , Midline cystMidline cyst

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HydromyeliaHydromyelia

SyringomyeliaSyringomyelia

SyringoSyringo bulbiabulbia

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Direct Direct parenchymalparenchymal injuryinjuryContusion: bruisingContusion: bruisingLaceration: tearingLaceration: tearing

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Contusion

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Plaque Plaque jaunejaune

Contusion

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Diffuse axonal injuryDiffuse axonal injury

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Diffuse axonal injuryDiffuse axonal injuryDeep Deep centroaxialcentroaxial white matter regionwhite matter region

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Traumatic vascular injuryTraumatic vascular injury

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Epidural hematomaEpidural hematoma

Associated skull fractureAssociated skull fractureMiddle Middle meningealmeningeal arteryarteryLucid intervalLucid interval

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Subdural hematomaSubdural hematomaPotential spacesPotential spaces--> Bridging veins Elder, infant> Bridging veins Elder, infantAcute subdural hematomaAcute subdural hematomaChronic subdural hematomaChronic subdural hematoma

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Chronic subdural hematomaChronic subdural hematomaMultiple episode of Multiple episode of rebleedingrebleedingOrganizingOrganizing

1wk 1wk --> Clot > Clot lysislysis2wks 2wks --> Fibroblast from > Fibroblast from meningesmeninges to hematomato hematoma22--3 months 3 months --> Early development of > Early development of hyalinizedhyalinizedconnective tissueconnective tissue

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Subarachnoid hemorrhageSubarachnoid hemorrhage

TraumaTrauma

Aneurysm/Vascular malformationAneurysm/Vascular malformation

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Trauma Trauma sequelesequelePost traumatic hydrocephalusPost traumatic hydrocephalusPunchPunch--drunk syndrome (dementia drunk syndrome (dementia pugilisticapugilistica))

HydrocephalusHydrocephalusThiningThining of corpus of corpus callosumcallosumDAIDAINeurofibrillaryNeurofibrillary tanglestanglesDiffuse ADiffuse Aββ--plaqueplaque

EpilepsyEpilepsyBrain tumor (Brain tumor (meningiomameningioma))Infectious diseaseInfectious diseasePsychiatric disorderPsychiatric disorder

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CerebrovascularCerebrovascular diseasediseaseCerebrovascularCerebrovascular accidentaccident (CVA) (CVA)

Ischemia and infarctionIschemia and infarction

Global cerebral ischemiaGlobal cerebral ischemia

Focal cerebral ischemiaFocal cerebral ischemia

Intracranial hemorrhageIntracranial hemorrhage

IntraparenchymalIntraparenchymal ((intracerebralintracerebral) hemorrhage) hemorrhage

Rupture Berry aneurysmRupture Berry aneurysm

Vascular malformation Vascular malformation

Hypertensive Hypertensive cerebrovascularcerebrovascular diseasedisease

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Global cerebral ischemiaGlobal cerebral ischemia

Diffuse hypoxic/ischemic encephalopathyDiffuse hypoxic/ischemic encephalopathy

Low flowLow flow

Respirator brainRespirator brain

Border zone (watershed) infarctionBorder zone (watershed) infarction

Most susceptibleMost susceptible

Pyramidal cells of Pyramidal cells of SommerSommer sector (CA1) of the sector (CA1) of the

hippocampus, Purkinje cell of cerebellum, hippocampus, Purkinje cell of cerebellum,

pyramidal neuron in pyramidal neuron in neocortexneocortex 27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 6060

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1.1. Early change:Early change: 1212--24 hrs24 hrsRed neuronRed neuronNeutrophilsNeutrophils

2.2. SubacuteSubacute change: 24hrschange: 24hrs--2 wks2 wksNecrosisNecrosisMacrophageMacrophageVascular proliferationVascular proliferationGliosisGliosis

3.3. Repair:Repair: after 2 weeksafter 2 weeksRemove all necrotic tissueRemove all necrotic tissueLoss normal organized CNS structureLoss normal organized CNS structureGliosisGliosisPseudolaminarPseudolaminar necrosisnecrosis

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Focal cerebral ischemiaFocal cerebral ischemiaMCAMCA**EmbolizationEmbolization**

Cardiac mural thrombi: MI, Cardiac mural thrombi: MI, valvularvalvular disease, AFdisease, AFThromboemboliThromboemboli: : atheromatousatheromatous plaqueplaqueParadoxical emboliParadoxical emboliEmboli associated with Emboli associated with SxSxOther material (tumor, fat, air)Other material (tumor, fat, air)

In situ thrombosisIn situ thrombosisAtherosclerosis: carotid bifurcation, origin of Atherosclerosis: carotid bifurcation, origin of MCA, basilar arteryMCA, basilar artery

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Non hemorrhagic infarctsNon hemorrhagic infarcts

First 6 hrs: difficultFirst 6 hrs: difficult

48 hrs: pale soft swollen, indistinct GW 48 hrs: pale soft swollen, indistinct GW junctiojunctio

22--10 days: gelatinous, friable, distinct10 days: gelatinous, friable, distinct

1010--3 wks: liquefies, fluid filled cavity3 wks: liquefies, fluid filled cavity

Hemorrhagic infarctsHemorrhagic infarcts

Reperfusion: collaterals, dissolution of Reperfusion: collaterals, dissolution of intravascular occlusionintravascular occlusion

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Bone marrow Bone marrow embolizationembolization

Fat embolismFat embolismFractures Fractures

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IntraparenchymalIntraparenchymal hemorrhagehemorrhage

HTHTPutamenPutamen* thalamus * thalamus ponspons cerebellarcerebellar hemispherehemisphereCharcotCharcot--Bouchard aneurysmBouchard aneurysmFusiformFusiformBasal gangliaBasal ganglia

GanglionicGanglionic hemorrhagehemorrhageBasal gangliaBasal gangliaThalamusThalamus

Lobar hemorrhageLobar hemorrhage

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Lobar hemorrhageLobar hemorrhage

Hemorrhagic diathesisHemorrhagic diathesis

NeoplasmsNeoplasms

Drug abuseDrug abuse

Infectious Infectious vasculitisvasculitis

Non infectiousNon infectious vasculitisvasculitis

Cerebral Cerebral amyloidamyloid angiopathyangiopathy

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AneurysmAneurysm

SaccularSaccular ((berryberry) ) abeurysmabeurysmMC subarachnoid hemorrhageMC subarachnoid hemorrhageCongenital Congenital

AtherosclerosiAtherosclerosissFusiformFusiform aneurysm, Basilar aaneurysm, Basilar a

MycoticMycoticTraumaticTraumaticDissectingDissecting

AnteriorAnterior ciculationciculation27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 7272

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Vascular malformationsVascular malformations

1.1. ArteriovenousArteriovenous malformations*malformations*

2.2. Cavernous Cavernous hemangiomashemangiomas

3.3. Capillary Capillary telangiectasiatelangiectasia

4.4. Venous Venous angiomasangiomas

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Hypertensive Hypertensive cerebrovascularcerebrovasculardiseasedisease

LacunarLacunar infarction (<15mm)infarction (<15mm)

Basal ganglia, thalamus. Internal capsule, deep white Basal ganglia, thalamus. Internal capsule, deep white

matter, matter, ponspons

Slit hemorrhageSlit hemorrhage

Hypertensive encephalopathyHypertensive encephalopathy

Diffuse cerebral dysfunctionDiffuse cerebral dysfunction

headache, confusion, headache, confusion, vomittingvomitting, convulsion, convulsion--> coma> coma

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TumorsTumorsSubtle Subtle histologichistologic distinctiondistinctionLow grade lesion sometimes infiltrateLow grade lesion sometimes infiltrateAnatomic siteAnatomic site --> prognosis> prognosisSpread through subarachnoid spacesSpread through subarachnoid spaces

1.1. GliomasGliomas2.2. Neuronal tumorsNeuronal tumors3.3. EmbryonalEmbryonal tumorstumors4.4. MeningiomaMeningioma5.5. MetastasisMetastasis

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GliomasGliomas

AstrocytomaAstrocytoma

PilocyticPilocytic, , AnaplasticAnaplastic, , GlioblastomaGlioblastoma

OligodendrogliomaOligodendroglioma

EpendymomaEpendymoma

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FibrillaryFibrillary ((diffusediffuse) ) astrocytomaastrocytoma

80% of adult primary brain tumor80% of adult primary brain tumor

44thth--66thth decadesdecades

Cerebral hemisphereCerebral hemisphere

Histology <Histology <--> prognosis> prognosis

II/IV Diffuse II/IV Diffuse astrocytomaastrocytoma

III/IV III/IV AnaplasticAnaplastic astrocytomaastrocytoma

IV/IVIV/IV GlioblastomaGlioblastoma

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GlioblastomaGlioblastoma

PalisadingPalisading necrosisnecrosis

Vascular proliferation Vascular proliferation

GlomeruloidGlomeruloid body body

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PilocyticPilocytic astrocytomaastrocytoma

Children, young adultChildren, young adultCerebellumCerebellum**, floor, floor--wall of 4wall of 4thth ventricleventricleOptic nerve, cerebral hemisphere Optic nerve, cerebral hemisphere

Gross:Gross: Cystic with mural noduleCystic with mural noduleSolid well circumscribedSolid well circumscribed

Micro:Micro: HairHair--like processlike processRosenthal fibersRosenthal fibersEosinophilicEosinophilic granular bodiesgranular bodiesMicrocystsMicrocysts

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OligodendrogliomaOligodendroglioma

44thth--55thth decadesdecades

Cerebral hemisphere: white matterCerebral hemisphere: white matter

Better prognosis>Better prognosis>astrocytomaastrocytoma

Gross:Gross: Infiltrative, gelatinous gray massInfiltrative, gelatinous gray mass

Micro:Micro: Similar to normal Similar to normal oligodendrocyteoligodendrocyte

Clear Clear cytoplasmiccytoplasmic halohalo

Delicate capillary networkDelicate capillary network

Calcifications (~90%)Calcifications (~90%)

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EpendymomaEpendymoma

11stst two decades: 4two decades: 4thth ventricleventricle

Adults: spinal cordAdults: spinal cord

SupratentorialSupratentorial, spinal better>cerebellum, spinal better>cerebellum

Gross:Gross: papillary/ circumscribed solidpapillary/ circumscribed solid

Micro:Micro: RosettesRosettes

PerivascularPerivascular pseudorosettespseudorosettes

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EmbryonalEmbryonal tumor: tumor: MedulloblastomaMedulloblastoma

20% of pediatric brain tumor20% of pediatric brain tumor

Cerebellum*Cerebellum*

UndifferentiatedUndifferentiated

Highly malignant, dismal prognosisHighly malignant, dismal prognosis

RadiosensitiveRadiosensitive--> 5 yr survival 75%> 5 yr survival 75%

Gross:Gross:

Children midline of cerebellumChildren midline of cerebellum

Adult: lateral Adult: lateral

Micro:Micro: Small blue cells, rosetteSmall blue cells, rosette

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 9393 27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 9494

MeningiomaMeningioma

MeningothelialMeningothelial cell (cell (arachnoidarachnoid))

External surface, ventricleExternal surface, ventricle

Loss of 22q (Loss of 22q (NF2NF2 22q12)22q12)

Slow growingSlow growing

ParasagittalParasagittal convexity, lateral convexity, wing of convexity, lateral convexity, wing of sphenoid, olfactory groove, foramen magnumsphenoid, olfactory groove, foramen magnum

F:M = 3:1F:M = 3:1 (10:1, spinal cord)(10:1, spinal cord)

Rapid growth during pregnancyRapid growth during pregnancy

MIB1 (Ki67)MIB1 (Ki67)

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Encapsulated mass, en plaque

Grade I – IV

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 9797

Metastatic tumorsMetastatic tumors¼¼-- ½½ of intracranial tumorsof intracranial tumors5 MC primary site (80%):5 MC primary site (80%):

LungLungBreastBreastSkin (melanoma)Skin (melanoma)KidneyKidneyGI tractGI tract

ChoriocarcinomaChoriocarcinomaIntraparenchymaIntraparenchyma, , meningesmeninges

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 9898

Metastatic tumorsMetastatic tumors

Sharply demarcatedSharply demarcated

GrayGray--white junctionwhite junction

Edema, reactive Edema, reactive gliosisgliosis, central necrosis, central necrosis

MeningealMeningeal carcinomatosiscarcinomatosis::

Brain, spinal cord, intracranial nerve rootBrain, spinal cord, intracranial nerve root

Lung: small cell CA, Lung: small cell CA, adenocaadenoca

Breast CABreast CA

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 9999 27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 100100

SchwannomaSchwannoma

SynSyn: : NeurilemmomaNeurilemmoma

Schwann cellSchwann cell

Symptoms: local compressionSymptoms: local compression

NF2NF2

CP angle, vestibular branch of VIIICP angle, vestibular branch of VIII

Acoustic Acoustic neuromaneuroma (vestibular (vestibular schwannomaschwannoma))

Gross: CircumscribedGross: Circumscribed

Micro: Micro: AntoniAntoni A (A (VerocayVerocay body), body), AntoniAntoni BB

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 101101www.robbinspathology,www.cumc.columbia.edu

Antoni A: cellular area, nuclear free zone, Verocay bodies

Antoni B: Loose cellular, microcysts, myxoid changes

Elongated cells, oval nucleiDegenerative change:

nulcear pleomorphism, xanthomatous change, vascular hyalinization

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 102102

NeurofibromaNeurofibroma

Skin: Skin: cutaneouscutaneous neurofibromaneurofibroma

Peripheral nerve: solitary Peripheral nerve: solitary neurofibromaneurofibroma

Sporadic or associated with Sporadic or associated with NF1NF1

Skin: nodules (Skin: nodules (pedunculatedpedunculated, , hyperpigmentedhyperpigmented))

PlexiformPlexiform neurofibromaneurofibroma: : NF1NF1--> > malignantmalignant

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 105105

Malignant peripheral nerve sheath tumorMalignant peripheral nerve sheath tumor

MPNST MPNST De no De no vovo: : NeurofibromaNeurofibroma, , plexiformplexiformAssociate with NF1Associate with NF1NF1, p53, p16NF1, p53, p16Highly malignantHighly malignantLocal invasive, recurrence, metastasisLocal invasive, recurrence, metastasisTriton tumorTriton tumor

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 106106

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 107107

Traumatic Traumatic neuromaneuroma

MortonMorton’’s s neuromaneuroma

Non Non neoplasticneoplastic proliferationproliferation

Response to injuryResponse to injury

Disorganized proliferation of proximal stumpDisorganized proliferation of proximal stump

Firm nodule, tender, painfulFirm nodule, tender, painful

Gross:Gross: circumscribed white gray nodulescircumscribed white gray nodules

Micro:Micro: haphazard proliferation of nerve fascicleshaphazard proliferation of nerve fascicles

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 108108

Traumatic Traumatic neuromaneuroma

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 109109

Type 1 NeurofibromatosisType 1 Neurofibromatosis

ADAD

NeurofibromasNeurofibromas ((plexiformplexiform, solitary), solitary)

GliomasGliomas of the optic nerveof the optic nerve

LischLisch nodulesnodules (iris)(iris)

CafCaféé au au laitlait spotsspots

Tend to have malignant transformationTend to have malignant transformation

NF1NF1 17q11.2 tumor suppressor: 17q11.2 tumor suppressor: neurofibrominneurofibromin

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 110110www4.ocn.ne.jpมwww.jyi.org

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 111111

Type 2 NeurofibromatosisType 2 Neurofibromatosis

ADAD

< NF1< NF1

Bilateral vestibular (acoustic) Bilateral vestibular (acoustic) schawannomaschawannoma

Multiple Multiple meningiomasmeningiomas

GliomasGliomas, , EpendymomaEpendymoma of the spinal cordof the spinal cord

SchwannosisSchwannosis (spinal cord)(spinal cord)

MeningioangiomatosisMeningioangiomatosis

GlialGlial hamartiahamartia27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 112112

Type 2 NeurofibromatosisType 2 Neurofibromatosis

HeterotopiaHeterotopia of of SchawannSchawann cells, cells, glialglial cellscells

Nonsense mutation, Nonsense mutation, missensemissense mutationmutation

NF2NF2 22q12: 22q12: merlinmerlin

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 113113

Tuberous sclerosisTuberous sclerosis

ADAD

HamartomasHamartomas and benign and benign neoplasmsneoplasms

CNS (cortical tubers, CNS (cortical tubers, subependymalsubependymalhamartomashamartomas))--> epilepsy, mental retardation> epilepsy, mental retardation

Renal Renal angiomyolipomaangiomyolipoma, retinal , retinal glialglial hamartomashamartomas, , cardiac cardiac rhabdomyomasrhabdomyomas

Cysts: liver kidney pancreasCysts: liver kidney pancreas

CutaneousCutaneous lesion: lesion: angiofibromaangiofibroma, , shagreenshagreenpatches, ashpatches, ash--leaf patches, leaf patches, subungualsubungual fibromafibroma

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 114114

Tuberous sclerosisTuberous sclerosis

Disruption of tumor suppressor geneDisruption of tumor suppressor gene

TSC1TSC1: : hamartinhamartin

TSC2TSC2: : tuberlintuberlin

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Von Von HippelHippel--LindauLindau DiseaseDisease

ADAD

HemangioblastomaHemangioblastoma: cerebellum, retina, : cerebellum, retina,

brainstem, spinal cordbrainstem, spinal cord

PheochromocytomaPheochromocytoma

Cysts; pancreas kidney, liverCysts; pancreas kidney, liver

Tend to develop renal cell carcinomaTend to develop renal cell carcinoma

MissenseMissense mutation in mutation in VHL VHL tumor suppressortumor suppressor

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 117117 27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 118118

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 119119

Primary disease of myelinPrimary disease of myelin

Disruption of neuronal communicationDisruption of neuronal communication

White matter disordersWhite matter disorders

DemyeliniatingDemyeliniating disease: acquired: MSdisease: acquired: MS

DysmyelinatingDysmyelinating disease: mutation: disease: mutation:

leukodystrophyleukodystrophy

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 120120

Multiple sclerosis (MS)Multiple sclerosis (MS)

MC* MC* demyelinatingdemyelinating disorderdisorder

Autoimmune: Autoimmune: env+geneticenv+genetic

New symptoms (relapse) New symptoms (relapse) --> remission (incomplete)> remission (incomplete)

Accumulation of increasing neurologic deficitAccumulation of increasing neurologic deficit

Any age, F:M = 2:1Any age, F:M = 2:1

HLAHLA--DR2DR2

TT--cell, macrophagecell, macrophage

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 121121

Multiple sclerosis (MS)Multiple sclerosis (MS)White matter diseaseWhite matter disease

Plaques:Plaques:Ventricles*Ventricles*

optic nerve, chiasm, optic nerve, chiasm, brainstem,tractsbrainstem,tracts, , cerebellum, spinal cord. cerebellum, spinal cord.

Active plaques:Active plaques:

Macrophage+myelinMacrophage+myelin debrisdebris

PerivascularPerivascular cuffscuffs

Axon preservedAxon preserved27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 122122

Plaque:well-circumscribed,irregular shape, slightly depressed glassy gray-tan lesion

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 123123

Multiple sclerosis (MS)Multiple sclerosis (MS)

Inactive plaques:Inactive plaques:

No inflammationNo inflammation

LittleLittle--no myelinno myelin

Prominent Prominent astrocyticastrocytic proliferation+ proliferation+ gliosisgliosis

Shadow plaques:Shadow plaques:

Not circumscribed borderNot circumscribed border

Thinned out myelin sheathsThinned out myelin sheaths

Incomplete loss/partial Incomplete loss/partial remyelinationremyelination27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 124124

Central Central pontinepontine demyelinolysisdemyelinolysis

Loss myelin/preserve axons, neuronsLoss myelin/preserve axons, neuronsRapid correction of Rapid correction of hyponatremiahyponatremiaPons*, elsewherePons*, elsewhereRapidly evolving quadriplegiaRapidly evolving quadriplegia

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 125125

Degenerative diseasesDegenerative diseases

Gray matter diseaseGray matter disease

Progressive neuronal lossProgressive neuronal loss

Secondary change in white matter tractsSecondary change in white matter tracts

1.1. CortexCortex

2.2. Basal ganglia and brain stemBasal ganglia and brain stem

3.3. SpinocerebellarSpinocerebellar

4.4. Motor neurons Motor neurons

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 126126

Alzheimer diseaseAlzheimer disease

MCMC** cause of dementia in elderlycause of dementia in elderly

Affecting cerebral cortexAffecting cerebral cortex

ForgetfulnessForgetfulness

Insidious impairment of intellectual function Insidious impairment of intellectual function

Alterations in mood and behaviorAlterations in mood and behavior

Progressive disorientationProgressive disorientation

Memory lossMemory loss

Aphasia Aphasia

ProfoundedProfounded disabled in next 5disabled in next 5--10 yrs10 yrs

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 127127

Alzheimer diseaseAlzheimer disease

Pathologic examination Pathologic examination --> definite> definite

Clinical + modern radiologic methodsClinical + modern radiologic methods

Sporadic> familial (5Sporadic> familial (5--10%)10%)

Rare before age of 50Rare before age of 50

AmyloidAmyloid precursor protein (APP)precursor protein (APP)

Chromosome 21 (Down syndrome>45 yr)Chromosome 21 (Down syndrome>45 yr)

ApolipoproteinApolipoprotein (ApoE4) (ApoE4) ChrChr 19 19 --> early onset> early onset

SORL1_> late onsetSORL1_> late onset27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 128128

AAββ::Small aggregates: Small aggregates:

Alter neuronal Alter neuronal transmissiontransmissionToxic to neurons Toxic to neurons and synaptic and synaptic endingsendings

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 129129

AAββ::Large aggregates: Large aggregates:

Form Form plaquesplaques

Neuronal deathNeuronal death

Local inflammatory responseLocal inflammatory response

Cell injuryCell injury

Alter regionAlter region--toto--region region commnicationcommnication through through mechanical effectmechanical effect

Form tangles (Form tangles (HyperphosphorelateHyperphosphorelate tautau protein )protein )

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 130130

Alzheimer diseaseAlzheimer disease

Gross:Gross: cerebral atrophycerebral atrophyFrontal/temporal/ temporalFrontal/temporal/ temporalSpare occipitalSpare occipitalHydrocephalus ex Hydrocephalus ex vacuovacuo

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 131131

Major microscopic abnormalities:

1.Neuritic (senile) plaques

2.Neurofibrillary tangles

3.Amyloid angiopathy

Diffuse plaques

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 132132missinglink.ucsf.edufaculty.washington.edu

Granulovacuolar degeneration:

Normal aging

AD: hippocampus, olfactory bulb

Hirano bodies

Major compotent: actin

Hippocampal pyramidal cells

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 133133

ParkinsonismParkinsonism

Mask Mask faciesfacies

Stooped postureStooped posture

Slowness voluntary movementSlowness voluntary movement

Festinating gaitFestinating gait

RigidityRigidity

PillPill--rolling tremorrolling tremor

1010--15%15%-->dementia (fluctuating courses/hallucination)>dementia (fluctuating courses/hallucination)

Pathologic evidence of Alzheimer diseasePathologic evidence of Alzheimer disease

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 134134

ParkinsonismParkinsonism

Idiopathic Parkinson diseaseIdiopathic Parkinson diseaseSporadic>familial (AD/AR)Sporadic>familial (AD/AR)

αα-- synuclein/parkinsynuclein/parkin

DopaminergicDopaminergic neuron in neuron in substantiasubstantia nigranigra

MPTP/ pesticide exposureMPTP/ pesticide exposure

Caffeine/ nicotine Caffeine/ nicotine --> protective> protective

RX RX --> L> L--dihydroxyphenylalaninedihydroxyphenylalanine (L(L--DOPA)DOPA)

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 135135

Gross: Pallor of substantia nigra, Locus ceruleusMicro: Loss of cathecholaminergic neurons,GliosisLewy body: basal nucleus of Meynert, sympathetic ganglia, cingulate/parahippocampal gyrus 27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 136136

Huntington diseaseHuntington disease

ADAD

TrinucleotideTrinucleotide (CAG) repeated mutation 4p16.3(CAG) repeated mutation 4p16.3

huntingtinhuntingtin

Progressive movement Progressive movement disorder+dementiadisorder+dementia

Degenerate striatum (Degenerate striatum (caudate+putamencaudate+putamen))

Chorea:Chorea:

Jerky, hyperkinetic, Jerky, hyperkinetic, dystonicdystonic movement movement

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 137137

Huntington diseaseHuntington disease

44thth--55thth decadesdecades

Depend on length of CAG Depend on length of CAG repeaterepeate

>70 adolescent>70 adolescent

Motor>cognitive impairmentMotor>cognitive impairment

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 138138

Huntington diseaseHuntington disease

Gross: Gross:

Striking atrophy on caudate/Striking atrophy on caudate/putamenputamen

GlobusGlobus palliduspallidus

Micro:Micro:

Severe neuronal lossSevere neuronal loss

GliosisGliosis

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 139139

Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis

ALSALSMC form of MC form of neurodegenerationneurodegeneration involving motor involving motor systemsystemMuscle atrophyMuscle atrophyHyperHyper--reflexiareflexia (loss (loss upper+lowerupper+lower motor neuron)motor neuron)Degeneration of the Degeneration of the corticospinalcorticospinal tracttractM>FM>F>5>5thth decadesdecades

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 140140

Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis

Sporadic>familial (AD 5Sporadic>familial (AD 5--10%)10%)

Chromosome 21 Chromosome 21

Superoxide dismutase (SOD1)Superoxide dismutase (SOD1)

Asymmetric weakness of handsAsymmetric weakness of hands

Cramping/spasticity of arms and legsCramping/spasticity of arms and legs

FasciculationsFasciculations

Respiratory musclesRespiratory muscles--> death> death

5 year survival5 year survival--50%50%

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 141141

Transmissible spongiform Transmissible spongiform encephalopathyencephalopathy ((PrionPrion diseasedisease))

CreutzfeldtCreutzfeldt--JakobJakob diseasedisease ((CJDCJD))

Variant CJDVariant CJD

GerstmannGerstmann--StrausslerStraussler--ScheinkerScheinker syndromesyndrome ((GSSGSS))

FatalFatal familialfamilial insomniainsomnia

KuruKuru

ScrapieScrapie:: sheep/goatsheep/goat

MinkMink transmissibletransmissible encephalopathyencephalopathy

Chronic wasting disease of deer and elkChronic wasting disease of deer and elk

Bovine spongiform encephalopathy (BSE)Bovine spongiform encephalopathy (BSE)27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 142142

PrionPrion diseasedisease

PRNPPRNP gene gene chrchr 20 20 PrPPrPcc --> > PrPPrPscsc,PrP,PrPresres

Resistant to protease digestionResistant to protease digestion

Other Other PrPPrPcc changechange

Low rate Low rate --> sporadic> sporadic

High rate High rate --> mutation> mutation

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 143143

PrionPrion diseasedisease

Accumulation of Accumulation of PrPPrPscsc in neural tissue in neural tissue --> cell injury> cell injury

CreutzfeldtCreutzfeldt--JakobJakob diseasedisease ((CJDCJD))

Rapidly progressive dementiaRapidly progressive dementia

85% sporadic 1: 1,000,000 85% sporadic 1: 1,000,000

FamilalFamilal form form

77thth decades decades

Subtle changes in memory and behavior Subtle changes in memory and behavior --> Rapidly > Rapidly progressive dementiaprogressive dementia

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 144144

CreutzfeldtCreutzfeldt--JakobJakob diseasedisease ((CJDCJD))

Startle Startle myoclonusmyoclonus, , cerebellarcerebellar dysfunctiondysfunction

Fatal in 7 monthsFatal in 7 months

SpongioformSpongioform transformation:transformation:

Cerebral cortex/deep gray matter structuresCerebral cortex/deep gray matter structures

Neuronal loss, reactive Neuronal loss, reactive gliosisgliosis

Expansion of vacuoles Expansion of vacuoles --> cyst (status > cyst (status spongiosusspongiosus))

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 145145

VariantVariant CreutzfeldtCreutzfeldt--JakobJakob diseasedisease ((vvCJDCJD))

Young adultsYoung adults

Exposure to BSE (cattle)Exposure to BSE (cattle)

Behavioral disorders in early stageBehavioral disorders in early stage

Neurologic syndrome progress slowlyNeurologic syndrome progress slowly

Pathologic/molecular finding: the samePathologic/molecular finding: the same

+ + Abundant cortical Abundant cortical amyloidamyloid plaquesplaques

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 146146

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 147147

GerstmannGerstmann--StrausslerStraussler--ScheinkerScheinker syndromesyndrome((GSSGSS))

Mutation in PRNP geneMutation in PRNP gene

Chronic Chronic cerebellarcerebellar ataxiaataxia

Progressive dementiaProgressive dementia

Clinical slower than CJDClinical slower than CJD

Death in several yearsDeath in several years

Micro: the sameMicro: the same

+ numerous + numerous amyloidamyloid ((KuruKuru) plaques/ tangles) plaques/ tangles27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 148148

Fatal familial insomniaFatal familial insomnia

Initial stageInitial stage-->Sleep disturbance >Sleep disturbance

<3 yr: neurological signs<3 yr: neurological signs

Ataxia, autonomic disturbance, stupor, comaAtaxia, autonomic disturbance, stupor, coma

Fatal sporadic insomniaFatal sporadic insomnia

Micro: Micro: NO NO spongioformspongioform pathologypathology

Neuronal loss, reactive Neuronal loss, reactive gliosisgliosis

Anterior ventral/Anterior ventral/dorsomedialdorsomedial nuclei of thalamusnuclei of thalamus

Inferior Inferior olivaryolivary nucleinuclei

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 149149

InfectionInfection

Routes of infection:Routes of infection:

1.1. HematogenousHematogenous spreadspread

2.2. Direct implantationDirect implantation

3.3. Local extensionLocal extension

4.4. Peripheral nervous systemPeripheral nervous system

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 150150

MeningitisMeningitis

MeningoencephalitisMeningoencephalitis

Chemical meningitisChemical meningitis

MeningealMeningeal carcinomatosiscarcinomatosis

MeningealMeningeal lymphomatosislymphomatosis

Infectious meningitisInfectious meningitis

Acute Acute pyogenicpyogenic (bacterial)(bacterial)

Aseptic meningitisAseptic meningitis (viral)(viral)

Chronic meningitis (Chronic meningitis (tuberculoustuberculous, , spirochetalspirochetal, , cryptococcalcryptococcal))

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 151151

Acute Acute pyogenicpyogenic ((bacterialbacterial) meningitis) meningitis

Escherichia coliEscherichia coli**Streptococcus group B*Streptococcus group B*

Streptococcus Streptococcus pneumoniaepneumoniae****--> > over convexitiesover convexities

ListeriaListeria monocytogenesmonocytogenesNeiseriaNeiseria meningitidismeningitidis******HaemophilusHaemophilus influenza influenza --> > basalbasal

MeningealMeningeal impairment, stiffness, headache, impairment, stiffness, headache, photophobiaphotophobia

CSF:CSF: Protein, Protein, glucoseglucose27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 152152

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 153153

Aseptic (Aseptic (viralviral) meningitis) meningitis

Less Less fulminantfulminant

Viral, NSAIDS, chemicalViral, NSAIDS, chemical

CSF: CSF: lymphocytosislymphocytosis, , proteinprotein, , sugar <sugar <-->>

Self limiting, symptomatic treatmentSelf limiting, symptomatic treatment

Gross:Gross: mild edemamild edema

Micro:Micro: mildmild--mod mod leptomeningealleptomeningeal L infiltrationL infiltration

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 154154

Acute focal Acute focal suppurativesuppurative infectioninfection

Brain abscess:Brain abscess:direct implant, local extensiondirect implant, local extensionFrontal>parietal>cerebellumFrontal>parietal>cerebellumCSF: CSF: protein <protein <-->sugar>sugar

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 155155

Subdural Subdural empyemaempyema: : bacteria, fungusbacteria, fungusExtraduralExtradural / spinal epidural abscess : / spinal epidural abscess : osteomyelitisosteomyelitis

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 156156

Chronic bacterial Chronic bacterial meningoencephalitismeningoencephalitis

Tuberculosis: Tuberculosis:

Base of the brain: gelatinous, Base of the brain: gelatinous, fibrinousfibrinous exudateexudate

MeningoencephalitisMeningoencephalitis*, *, ObliterativeObliterative endarteritis, endarteritis,

TuberculomaTuberculoma

CpxCpx: :

ArachnoidArachnoid fibrosis fibrosis --> hydrocephalus> hydrocephalus

ObliterativeObliterative endarteritis endarteritis --> infarction> infarction

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 157157 27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 158158

NeurosyphilisNeurosyphilis = Tertiary syphilis= Tertiary syphilis

1.1. MeningovascularMeningovascular neurosyphilisneurosyphilis

2.2. Paretic Paretic neurosyphilisneurosyphilis

3.3. TabesTabes dorsalisdorsalis

MeningovascularMeningovascular::

Chronic meningitis: base/convexities/spinal cordChronic meningitis: base/convexities/spinal cord

ObliterativeObliterative ((HeubnerHeubner) endarteritis) endarteritis

Plasma cell/ lymphocytesPlasma cell/ lymphocytes

Cerebral Cerebral gummagumma

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 159159

Paretic Paretic neurosyphilisneurosyphilisInvasion Invasion T. T. pallidumpallidumGranular Granular ependymitisependymitis -->hydrocephalus >hydrocephalus General paresis of the insane: delusion of General paresis of the insane: delusion of grandeur, dementia, loss mental/physicalgrandeur, dementia, loss mental/physical

TabesTabes dorsalisdorsalisDamage sensory nerves in dorsal rootDamage sensory nerves in dorsal rootLoss Joint position sense Loss Joint position sense --> ataxia> ataxiaLoss of pain sensationLoss of pain sensation--> > ChacotChacot jointjoint--> lightning pain> lightning painLoss DTRLoss DTR

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 160160

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 161161

Viral Viral meningoencephalitismeningoencephalitis

MeningoencephalitisMeningoencephalitis

EncephalomyelitisEncephalomyelitis

Histology:Histology:

Perivascular/parenchymalPerivascular/parenchymal mononuclear cell mononuclear cell

infiltratesinfiltrates

GlialGlial reaction: reaction: microglialmicroglial nodulenodule

NeuronophagiaNeuronophagia

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 162162

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 163163

Herpes simplex virus type 1Herpes simplex virus type 1

EncephalitisEncephalitis

Any age group: children/young adult*Any age group: children/young adult*

AlteratingAlterating mood, memory, behaviormood, memory, behavior

Orbital Orbital gyrigyri of frontal lobeof frontal lobe

Medial regions of temporal lobeMedial regions of temporal lobe

Necrotizing and hemorrhagicNecrotizing and hemorrhagic

PerivascularPerivascular cuffingcuffing

CowdryCowdry type A in neurons/type A in neurons/gliaglia27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 164164

Herpes simplex virus type 2Herpes simplex virus type 2MeningitisMeningitis--AdultAdult

EncephalitisEncephalitis--vaginal delivered neonatevaginal delivered neonate

AIDSAIDS--acute hemorrhagic necrotizing encephalitisacute hemorrhagic necrotizing encephalitis

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 165165

VaricellarVaricellar--zoster virus (Herpes zoster)zoster virus (Herpes zoster)

ImmunosuppressedImmunosuppressed –– herpes zoster encephalitisherpes zoster encephalitisInclusion bodies in in Inclusion bodies in in gliaglia and neuronand neuron

CytomegalovirusCytomegalovirus

ImmunosuppressedImmunosuppressed--subacutesubacute encephalitisencephalitisFetus Fetus -- In In uteroutero

--> > periventricularperiventricular necrosis + severe brain destructionnecrosis + severe brain destruction--> > microcephalymicrocephaly + + periventricularperiventricular calcificationcalcification

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 166166

CytomegalovirusCytomegalovirus

Virus: Virus: paraventricularparaventricular subependymalsubependymal regionregion

Severe hemorrhagic necrotizing Severe hemorrhagic necrotizing

ventriculoencephalitisventriculoencephalitis

Choroid Choroid plexitisplexitis

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 167167

PoliomyelitisPoliomyelitis

Anterior horn cell motor neuron of spinal cordAnterior horn cell motor neuron of spinal cordPerivascularPerivascular cuff, cuff, neuronophagianeuronophagiaPosterior horn/ motor cranial nucleiPosterior horn/ motor cranial nucleiLong term: neuronal loss, Long term: neuronal loss, gliosisgliosis, atrophy, atrophy

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 168168

RabiesRabies

Neuronal degeneration + inflammationNeuronal degeneration + inflammation

Midbrain, floor of 4Midbrain, floor of 4thth ventricle, medullaventricle, medulla

Basal ganglia, spinal cord, dorsal root gangliaBasal ganglia, spinal cord, dorsal root ganglia

NegriNegri bodybody –– inflammation:inflammation:

Pyramidal neuron Pyramidal neuron –– hippocampushippocampus

Purkinje cell Purkinje cell -- medullamedulla

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 169169

HIVHIV

Direct effect/ opportunistic infection/ tumorsDirect effect/ opportunistic infection/ tumors

Aseptic HIVAseptic HIV--1 meningitis1 meningitis

10%: 110%: 1--2 wks after 2 wks after seroconversionseroconversion

mild lymphocytic meningitismild lymphocytic meningitis

perivascularperivascular cuffingcuffing

myelin lossmyelin loss

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 170170

HIVHIV

HIVHIV--1 1 meningoencephalitismeningoencephalitis ((subacutesubacute encephalitis)encephalitis)

AIDS dementia complex: mental slowing, AIDS dementia complex: mental slowing,

memory loss mood memory loss mood disterbancedisterbance

Chronic inflammatory cell infiltrationChronic inflammatory cell infiltration

MicroglialMicroglial nodule + multinucleated giant cellsnodule + multinucleated giant cells

Vacuolar Vacuolar myelopathymyelopathy

Tracts of spinal cordTracts of spinal cord

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 171171

Progressive multifocal Progressive multifocal leukoencephalopathyleukoencephalopathy

PML: JC PML: JC polyomaviruspolyomavirus

ImmunosuppressedImmunosuppressed: CML, : CML, chemoRXchemoRX, AIDS, AIDS

65% of normal people: exposure by 14 yr65% of normal people: exposure by 14 yr

ReactivationReactivation

OligodendrocyteOligodendrocyte--> > demyelinationdemyelination

CT: CT:

extensive multifocal ring enhancing lesion in extensive multifocal ring enhancing lesion in hemispheric/ hemispheric/ cerebellarcerebellar white matterwhite matter

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 172172

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 173173

Fungal encephalitisFungal encephalitis

GranulomasGranulomas, abscesses, meningitis, abscesses, meningitisCandida Candida albicansalbicans

Multiple Multiple microabscessesmicroabscesses w/wow/wo granulomagranulomaMucorMucorAspergillusAspergillus fumigatusfumigatus

Septic hemorrhagic infarctionSeptic hemorrhagic infarctionCryptococcus Cryptococcus neoformansneoformansHistoplasmaHistoplasma capsulatumcapsulatum

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 175175

Cerebral toxoplasmosisCerebral toxoplasmosis

ToxoplasmaToxoplasma gondiigondii

AIDSAIDS

CT/MR: multiple ring enhancing lesionCT/MR: multiple ring enhancing lesion

Gross: Gross:

Abscesses, GrayAbscesses, Gray--white junction, deep gray nucleiwhite junction, deep gray nuclei

Micro: Micro:

Central necrosis, Central necrosis, petichiaepetichiae hemorrhage, hemorrhage,

tachyzoitetachyzoite, , bradyzoitebradyzoite27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 176176

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 177177

CysticercosisCysticercosis

TeniaTenia soliumsolium

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 178178

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 179179

Amebic Amebic meningoencephalitismeningoencephalitis

NaegleriaNaegleria sppspp

Swimming in Swimming in nonflowingnonflowing fresh waterfresh water

Fatal encephalitisFatal encephalitis

AcanthamoebaAcanthamoeba sppspp

Chronic Chronic granulomatousgranulomatous meningoencephalitismeningoencephalitis

27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 180180www.fujita-hu.ac.jp

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27/10/5127/10/51 Jantima Tanboon, MDJantima Tanboon, MD 181181Thank you for your attentionThank you for your attention