Cns

Pathology of thePathology of the
Nervous SystemNervous System
Karen SantaCruz MDKaren SantaCruz MD
Brent Clark MD, PhDBrent Clark MD, PhD

Pathology of the Nervous SystemPathology of the Nervous System
 IntroductionIntroduction
 IncreasedIncreased
intracranialintracranial
pressurepressure
 Vascular andVascular and
circulatorycirculatory
disordersdisorders
 TraumaTrauma
 InfectionsInfections
 TumorsTumors
 DemyelinatingDemyelinating
diseasesdiseases
 DegenerativeDegenerative
diseasesdiseases
 DevelopmentalDevelopmental
AbnormalitiesAbnormalities

Hematoxylin and Eosin Luxol fast-blue-PASLuxol fast-blue-PAS
BielschowskyBielschowsky

Cell typesCell types
1.1. Neuron:Neuron: functions in neural transmission, mostfunctions in neural transmission, most
vulnerable cell, limited regenerationvulnerable cell, limited regeneration
2.2. AstrocyteAstrocyte: major reactive cell of CNS forms ‘scar’: major reactive cell of CNS forms ‘scar’
3.3. OligodendrocyteOligodendrocyte: highly vulnerable, limited: highly vulnerable, limited
proliferation, forms myelin sheathproliferation, forms myelin sheath
4.4. Ependymal cellEpendymal cell: vulnerable, limited regeneration,: vulnerable, limited regeneration,
lines ventricles (ependymal granulations)lines ventricles (ependymal granulations)
5.5. Microglial cellMicroglial cell: monocyte/macrophage (bone: monocyte/macrophage (bone
marrow) derived phagocytic cell, antigenmarrow) derived phagocytic cell, antigen
presentation, producer of cytokines,presentation, producer of cytokines,
inflammatory cellinflammatory cell

IntroductionIntroduction
 Cellular reactions of the central nervous systemCellular reactions of the central nervous system
 Neurons: permanentNeurons: permanent
 Axonal retraction (axonal spheroids)Axonal retraction (axonal spheroids)
 Ischemic cell changesIschemic cell changes
 Atrophy and degenerationAtrophy and degeneration
 Intraneuronal deposits and inclusionsIntraneuronal deposits and inclusions
(neurodegenerative diseases)(neurodegenerative diseases)
 Glia: proliferate, form glial ‘scar’Glia: proliferate, form glial ‘scar’

Nissl substanceNissl substance

Ventricular liningVentricular lining

Mechanisms of dysfunction causingMechanisms of dysfunction causing
diseasedisease
 Pathophysiological (toxic/metabolic)Pathophysiological (toxic/metabolic)
 StructuralStructural
Focal lesions correlate with localizing symptomsFocal lesions correlate with localizing symptoms
System degenerations correlate with functionallySystem degenerations correlate with functionally
localizing symptoms (ie motor neuron disease)localizing symptoms (ie motor neuron disease)
 Increased intracranial pressure (generalized orIncreased intracranial pressure (generalized or
focal), can cause global symptoms or brainfocal), can cause global symptoms or brain
herniation since the volume of the brain is fixed byherniation since the volume of the brain is fixed by
the skullthe skull

Increased intracranialIncreased intracranial
pressurepressure
HeadacheHeadache
VomitingVomiting
Decreased Level of ConsciousnessDecreased Level of Consciousness
PapilledemaPapilledema
HerniationHerniation

Causes of Cerebral EdemaCauses of Cerebral Edema
 GeneralizedGeneralized
(frequently(frequently
cytotoxic)cytotoxic)
 HypoxiaHypoxia
 ToxinsToxins
 EncephalitisEncephalitis
 TraumaTrauma
 Focal (often vasogenic)Focal (often vasogenic)
 InfarctionInfarction
 Injury/contusionInjury/contusion
 Mass—neoplastic,Mass—neoplastic,
infectious (cerebralinfectious (cerebral
abscess), hematomaabscess), hematoma

TYPES OF HERNIATIONTYPES OF HERNIATION
1.1. SubfalcineSubfalcine
(cingulate)(cingulate)
2.2. TranstentorialTranstentorial
(uncal)(uncal)
3.3. TonsillarTonsillar
(foramen(foramen
magnum)magnum)
4.4. ExtracranialExtracranial

TRANSTENTORIAL (UNCAL)TRANSTENTORIAL (UNCAL)
HERNIATIONHERNIATION
SHIFT OF THE BRAIN FROM THE MIDDLE TOSHIFT OF THE BRAIN FROM THE MIDDLE TO
THE POSTERIOR FOSSA THROUGH THETHE POSTERIOR FOSSA THROUGH THE
TENTORIAL INCISURATENTORIAL INCISURA
MAY BE UNILATERAL OR “CENTRAL”MAY BE UNILATERAL OR “CENTRAL”
SECONDARY EFFECTS INCLUDE:SECONDARY EFFECTS INCLUDE:
Compression of the third cranial nerve(s)Compression of the third cranial nerve(s)
Duret hemorrhages in midline rostral brainstemDuret hemorrhages in midline rostral brainstem
Compression of the contralateral cerebral peduncleCompression of the contralateral cerebral peduncle
(Kernohan’s notch)(Kernohan’s notch)
Compression of the posterior cerebral artery withCompression of the posterior cerebral artery with
infarction of the medial occipital lobeinfarction of the medial occipital lobe

UNCAL HERNIATIONUNCAL HERNIATION
Normal uncusNormal uncus Herniated rightHerniated right
uncusuncus

DURET HEMORRHAGESDURET HEMORRHAGES
Midline Duret hemorrhages plus Kernohan’sMidline Duret hemorrhages plus Kernohan’s
notch in the right cerebral pedunclenotch in the right cerebral peduncle

HYDROCEPHALUSHYDROCEPHALUS
DILATATION OF THE VENTRICULARDILATATION OF THE VENTRICULAR
SYSTEMSYSTEM
NONCOMMUNICATING: Due toNONCOMMUNICATING: Due to
obstruction within the ventricular system,obstruction within the ventricular system,
e.g., tumor, aqueductal stenosise.g., tumor, aqueductal stenosis
COMMUNICATING: Due to obstruction ofCOMMUNICATING: Due to obstruction of
CSF flow in the subarachnoid space withCSF flow in the subarachnoid space with
decreased reabsorptiondecreased reabsorption

COMMUNICATINGCOMMUNICATING
HYDROCEPHALUSHYDROCEPHALUS
Dilatation of the entire ventricular system including theDilatation of the entire ventricular system including the
aqueduct and fourth ventricular foramina. There isaqueduct and fourth ventricular foramina. There is
thickening and scarring of the meninges, secondary tothickening and scarring of the meninges, secondary to
previous subarachnoid hemorrhageprevious subarachnoid hemorrhage

Summary: Microscopic and grossSummary: Microscopic and gross
brain abnormalitiesbrain abnormalities
 Cell types: Function and proliferative capacityCell types: Function and proliferative capacity
 Mechanisms of CNS dysfunction:Mechanisms of CNS dysfunction:
 Pathophysiological “invisible” lesions: metabolic, toxicPathophysiological “invisible” lesions: metabolic, toxic
 Structural “visible” abnormalities: mass, edema,Structural “visible” abnormalities: mass, edema,
hydrocephalus, cytologic abnormalities.hydrocephalus, cytologic abnormalities.
 Increased intracranial pressureIncreased intracranial pressure
 Causes of cerebral edema: focal and generalizedCauses of cerebral edema: focal and generalized
 Types of herniation: cingulate, uncal, tonsillarTypes of herniation: cingulate, uncal, tonsillar
 Hydrocephalus: non-communicating and communicatingHydrocephalus: non-communicating and communicating

Vascular andVascular and
Circulatory DisordersCirculatory Disorders
Ischemia/InfarctionIschemia/Infarction
Transient Ischemic AttacksTransient Ischemic Attacks
HemorrhageHemorrhage

Stroke: Ischemia/InfarctStroke: Ischemia/Infarct
 Atherosclerosis: NarrowingAtherosclerosis: Narrowing
 Thrombosis: Damages vessel, infarcts areThrombosis: Damages vessel, infarcts are
non-hemorrhagicnon-hemorrhagic
 Embolism: Heart valves, plaquesEmbolism: Heart valves, plaques
(frequently hemorrhagic)(frequently hemorrhagic)
 Vasospasm: Rare, but common afterVasospasm: Rare, but common after
subarachnoid hemorrhagesubarachnoid hemorrhage
 Hypertensive vasculopathy: LacunarHypertensive vasculopathy: Lacunar
infarctsinfarcts

RISK FACTORSRISK FACTORS
atherosclerosisatherosclerosis

RISK FACTOR: atherosclerosisRISK FACTOR: atherosclerosis

EMBOLIC INFARCTSEMBOLIC INFARCTS
TYPICALLYTYPICALLY
ARE HEMORRHAGICARE HEMORRHAGIC

RISK FACTORS:RISK FACTORS:
hypertension (lacunar infarcts)hypertension (lacunar infarcts)
Lacunar infarct of theLacunar infarct of the
globus pallidusglobus pallidus
Lacunar infarct of theLacunar infarct of the
ponspons

Other causes of ischemiaOther causes of ischemia
 Systemic Hypotension: Results in watershedSystemic Hypotension: Results in watershed
infarctsinfarcts
 Hypoxia or Anoxia: Lack of oxygen or poorHypoxia or Anoxia: Lack of oxygen or poor
perfusion after MI results in watershed infarctsperfusion after MI results in watershed infarcts
and/or damage in vulnerable regions, ieand/or damage in vulnerable regions, ie
hippocampus and cerebellumhippocampus and cerebellum
 Venous thrombosis: Rare, causes hemorrhagicVenous thrombosis: Rare, causes hemorrhagic
infarcts, consider coagulopathyinfarcts, consider coagulopathy

ANASTOMOSES BETWEENANASTOMOSES BETWEEN
TERMINAL BRANCHES OFTERMINAL BRANCHES OF
MAJOR CEREBRAL ARTERIESMAJOR CEREBRAL ARTERIES

VASCULAR WATERSHEDSVASCULAR WATERSHEDS

VENOUSVENOUS
CIRCULATIONCIRCULATION

VENOUS INFARCTIONVENOUS INFARCTION
 Venous infarction usuallyVenous infarction usually
results from venous sinusresults from venous sinus
thrombosisthrombosis
 Risk factors include aRisk factors include a
number of states thatnumber of states that
result in hyperviscosityresult in hyperviscosity
or increased coagulabilityor increased coagulability
 Grossly they are veryGrossly they are very
hemorrhagichemorrhagic

Transient Ischemic AttacksTransient Ischemic Attacks
 Lasts less than 24 hours by definitionLasts less than 24 hours by definition
 Attributed to transient embolizationAttributed to transient embolization
 Occurs in patients with atheroscleroticOccurs in patients with atherosclerotic
stenosisstenosis
 Harbinger of cerebral infarctionHarbinger of cerebral infarction

Summary: Strokes due toSummary: Strokes due to
ischemia/infarctionischemia/infarction
 Large vessel atherosclerotic disease (non-Large vessel atherosclerotic disease (non-
hemorrhagic)hemorrhagic)
 Embolic (hemorrhagic)Embolic (hemorrhagic)
 Hypertensive (hemorrhages and lacunes)Hypertensive (hemorrhages and lacunes)
 Vasospasm (2° to subarachnoid hemorrhage)Vasospasm (2° to subarachnoid hemorrhage)
 Watershed infarcts: hypotension and hypoxiaWatershed infarcts: hypotension and hypoxia
 Venous thrombosis (rare, hemorrhagic)Venous thrombosis (rare, hemorrhagic)
 TIA: clears in 24 hours -by definition, oftenTIA: clears in 24 hours -by definition, often
associated with large vessel diseaseassociated with large vessel disease

Strokes Due toStrokes Due to
HypertensionHypertension
AneurysmsAneurysms
Vascular MalformationsVascular Malformations
Bleeding DiathesisBleeding Diathesis
TraumaTrauma

HYPERTENSIVEHYPERTENSIVE
HEMORRHAGEHEMORRHAGE
lenticulostriate arterieslenticulostriate arteries

SACCULAR ANEURYSMSSACCULAR ANEURYSMS

SUBARACHNOID HEMORRHAGESUBARACHNOID HEMORRHAGE
rupture of saccular (berry) aneurysmrupture of saccular (berry) aneurysm

MYCOTIC ANEURYSMMYCOTIC ANEURYSM
(bacterial)

VASCULAR MALFORMATIONVASCULAR MALFORMATION
AS A SOURCE OF HEMORRHAGEAS A SOURCE OF HEMORRHAGE
arteriovenous malformation (AVM)arteriovenous malformation (AVM)

BLOOD DYSCRASIASBLOOD DYSCRASIAS
AS A CAUSE OF HEMORRHAGEAS A CAUSE OF HEMORRHAGE
thrombocytopeniathrombocytopenia

Summary: Strokes due toSummary: Strokes due to
hemorrhagehemorrhage
 Hypertension: Most common cause of brainHypertension: Most common cause of brain
hemorrhage, sites include basal ganglia, pons,hemorrhage, sites include basal ganglia, pons,
cerebellum and cerebral white mattercerebellum and cerebral white matter
 Aneurysms:Aneurysms:
 Berry aneurysm: Most common type, causesBerry aneurysm: Most common type, causes SAHSAH
 Mycotic aneurysm: Rare, parenchymal bleed, bacterialMycotic aneurysm: Rare, parenchymal bleed, bacterial
 Atherosclerotic: Rarely bleed, may cause mass effect,Atherosclerotic: Rarely bleed, may cause mass effect,
fusiformfusiform
 Vascular malformations and clottingVascular malformations and clotting
abnormalitiesabnormalities

Closed Head InjuryClosed Head Injury
ConcussionConcussion
 Immediate and temporary disturbance of brainImmediate and temporary disturbance of brain
function.function.
 Grading (1.Grading (1. mildmild: no LOC/smpt <15 min, 2.: no LOC/smpt <15 min, 2.
modmod: no LOC/smpt >15min, 3.: no LOC/smpt >15min, 3. severesevere: any LOC): any LOC)
 CauseCause
 Shearing of axonsShearing of axons
 Signs: Amnesia, confusion, headache, visualSigns: Amnesia, confusion, headache, visual
disturbances, nausea, vomiting, dizzinessdisturbances, nausea, vomiting, dizziness

 Epidural hematomaEpidural hematoma: Middle meningeal artery: Middle meningeal artery
tear (temporal bone fracture), accumulatestear (temporal bone fracture), accumulates
rapidly (arterial)rapidly (arterial)
 Subdural hematomaSubdural hematoma: Shearing of bridging: Shearing of bridging
veins, accumulate in hours to days (rarelyveins, accumulate in hours to days (rarely
weeks+)weeks+)
 Subarachnoid hemorrhageSubarachnoid hemorrhage: Occurs with: Occurs with
contusions or intraparenchymal hemorrhagecontusions or intraparenchymal hemorrhage
(also with berry aneurysms)(also with berry aneurysms)

TRAUMA AS A CAUSE OFTRAUMA AS A CAUSE OF
HEMORRHAGEHEMORRHAGE
subdural hematomasubdural hematoma

 ContusionsContusions: Brain against bone, coup (at site: Brain against bone, coup (at site
of impact)/contrecoup (side opposite impact)of impact)/contrecoup (side opposite impact)
 Intracerebral hemorrhageIntracerebral hemorrhage: Shearing of brain: Shearing of brain
vessels, high impactvessels, high impact
 Diffuse Axonal InjuryDiffuse Axonal Injury: Shearing of axons: Shearing of axons
results in post-traumatic neurologic deficitsresults in post-traumatic neurologic deficits
 Cerebral EdemaCerebral Edema: Occurs with and without an: Occurs with and without an
obvious structural lesionobvious structural lesion
 Note: Can occur without evidence of hemorrhageNote: Can occur without evidence of hemorrhage

TRAUMA AS A CAUSE OFTRAUMA AS A CAUSE OF
HEMORRHAGE: contusionsHEMORRHAGE: contusions

Other traumatic injuriesOther traumatic injuries
 Penetrating injuries: Bullets, bone fragments,Penetrating injuries: Bullets, bone fragments,
result in laceration with the potential forresult in laceration with the potential for
infectioninfection
 Spinal cord injury: Fractures, vertebralSpinal cord injury: Fractures, vertebral
dislocation, penetrating injury, the spinal corddislocation, penetrating injury, the spinal cord
may be crushed or the site of hemorrhagemay be crushed or the site of hemorrhage

Summary: TraumaSummary: Trauma
 Closed head injuries:Closed head injuries:
 Sites (epidural, subdural, subarachnoid,Sites (epidural, subdural, subarachnoid,
parenchymal) and typical etiologyparenchymal) and typical etiology
 Contusion, hemorrhage, diffuse axonal injury,Contusion, hemorrhage, diffuse axonal injury,
edemaedema
 Penetrating injuries:Penetrating injuries:
 Causes and risks (infection)Causes and risks (infection)
 Spinal cord injuriesSpinal cord injuries

InfectionsInfections
MeningitisMeningitis
BacterialBacterial
TuberculousTuberculous
FungalFungal
ViralViral
Cerebral abscessCerebral abscess
SubduralSubdural
empyemaempyema
CerebritisCerebritis
Viral encephalitisViral encephalitis

Infections: Route of entryInfections: Route of entry
 Hematogenous (most common)Hematogenous (most common)
 Localized source: abscess, heart valve, lung infectionLocalized source: abscess, heart valve, lung infection
 Other: mosquitos, needlesOther: mosquitos, needles
 Direct implantation (trauma)Direct implantation (trauma)
 Local extension (ear infectionLocal extension (ear infection abscess)abscess)
 Axonal transport (rabies, HSV)Axonal transport (rabies, HSV)

MeningitisMeningitis
 Inflammation of the meningesInflammation of the meninges
 FeverFever
 HeadacheHeadache
 Stiff neckStiff neck
 Decreased level of consciousnessDecreased level of consciousness
 Bacterial (purulent)Bacterial (purulent)
 Tuberculous (granulomatous)Tuberculous (granulomatous)
 Fungal (granulomatous)Fungal (granulomatous)

Bacterial MeningitisBacterial Meningitis
 Neonates: E. Coli, group B streptococciNeonates: E. Coli, group B streptococci
 Infants and children: Hemophilus influenzaInfants and children: Hemophilus influenza
(before immunization)(before immunization)
 Young adults: Neisseria meningitidisYoung adults: Neisseria meningitidis
 Adults: Streptococcus pneumoniae and ListeriaAdults: Streptococcus pneumoniae and Listeria
monocytogenesmonocytogenes

Meningitis: CSF findingsMeningitis: CSF findings
 Increased white blood cellsIncreased white blood cells
 Neutrophils withNeutrophils with bacterialbacterial meningitismeningitis
 Mononuclear cells (lymphocytes andMononuclear cells (lymphocytes and
macrophages) withmacrophages) with TB and fungalTB and fungal infectionsinfections
 Lymphocytes withLymphocytes with viralviral infectioninfection
 Increased protein (mild with viral)Increased protein (mild with viral)
 Reduced glucose withReduced glucose with bacterialbacterial meningitismeningitis

PURULENT (BACTERIAL)PURULENT (BACTERIAL)
MENINGITISMENINGITIS

PURULENT MENINGITISPURULENT MENINGITIS

GRANULOMATOUS MENINGITIS:GRANULOMATOUS MENINGITIS:
tuberculosistuberculosis

GRANULOMATOUSGRANULOMATOUS
H&EH&E Acid FastAcid Fast

GRANULOMATOUSGRANULOMATOUS
Sequelae:Sequelae:
VasculitisVasculitis
Small infarctsSmall infarcts
Cranial neuropathiesCranial neuropathies

ASEPTIC (VIRAL)ASEPTIC (VIRAL)

Cerebral AbscessCerebral Abscess
 Localized (contained) infectionLocalized (contained) infection
 Hematogenous spread (heart valves), penetratingHematogenous spread (heart valves), penetrating
wound, paranasal sinuses, middle earwound, paranasal sinuses, middle ear
 Oral flora may be the source of an abscess afterOral flora may be the source of an abscess after
dental manipulationdental manipulation
 Organisms are mixed and frequently anaerobicOrganisms are mixed and frequently anaerobic
 Surrounding cerebral edema is commonSurrounding cerebral edema is common
 CSF is frequently sterileCSF is frequently sterile

PURULENT CEREBRALPURULENT CEREBRAL
ABSCESSABSCESS

Cerebritis in Immune-compromisedCerebritis in Immune-compromised
PatientsPatients
 Fungal InfectionsFungal Infections
 AspergillusAspergillus
 CandidaCandida
 MucorMucor
 ProtozoalProtozoal
 ToxoplasmaToxoplasma
 Ameba infections can be seen inAmeba infections can be seen in
immunocompromised patients and rarelyimmunocompromised patients and rarely
non-immunocompromised individualsnon-immunocompromised individuals

Viral infectionViral infection
 Route of entryRoute of entry
 May be blood borne, respiratory or fecal/oralMay be blood borne, respiratory or fecal/oral
 Rabies-peripheral nerveRabies-peripheral nerve
 Acute viral encephalitisAcute viral encephalitis
 Herpes-activation of latent infectionHerpes-activation of latent infection
 Arbovirus-mosquito borne (West Nile virus)Arbovirus-mosquito borne (West Nile virus)
 Polio-enteric virus with neuronal tropismPolio-enteric virus with neuronal tropism
 Immunocompromised hostsImmunocompromised hosts
 CMVCMV
 HSV/VZVHSV/VZV
 PMLPML
 HIV encephalitis (HIVE)HIV encephalitis (HIVE)

ACUTE (VIRAL) ENCEPHALITISACUTE (VIRAL) ENCEPHALITIS
microscopic featuresmicroscopic features
Lymphocytic infiltratesLymphocytic infiltrates Microglial proliferationMicroglial proliferation
with microglial noduleswith microglial nodules

ACUTE (VIRAL) ENCEPHALITISACUTE (VIRAL) ENCEPHALITIS
Herpes simplexHerpes simplex

OPPORTUNISTIC VIRAL INFECTIONS:OPPORTUNISTIC VIRAL INFECTIONS:
Progressive multifocal leukoencephalopathyProgressive multifocal leukoencephalopathy
(JC virus)(JC virus)

Progressive multifocalProgressive multifocal
leukoencephalopathyleukoencephalopathy

OPPORTUNISTIC INFECTIONS:OPPORTUNISTIC INFECTIONS:
ToxoplasmosisToxoplasmosis

OPPORTUNISTICOPPORTUNISTIC
INFECTIONS: ToxoplasmosisINFECTIONS: Toxoplasmosis
Bradyzoites with cystsBradyzoites with cysts

OPPORTUNISTICOPPORTUNISTIC
INFECTIONSINFECTIONS
ToxoplasmosisToxoplasmosis
Necrotizing lesionNecrotizing lesion Immunoperoxidase forImmunoperoxidase for
H&EH&E Toxo. tachyzoitesToxo. tachyzoites

OPPORTUNISTIC INFECTIONSOPPORTUNISTIC INFECTIONS
Fungal cerebritis : AspergillusFungal cerebritis : Aspergillus

Summary: InfectionsSummary: Infections
 Meningitis: Definition, CSF findingsMeningitis: Definition, CSF findings
 Abscess: Definition, etiologyAbscess: Definition, etiology
 Viral meningitis: Routes of entry (arbo-Viral meningitis: Routes of entry (arbo-
mosquitos)mosquitos)
 Viral encephalitis: Rabies, HSV, arbovirusesViral encephalitis: Rabies, HSV, arboviruses
 Spinal cord: PolioSpinal cord: Polio
 Infections in immunocompromised hostsInfections in immunocompromised hosts
 Cerebritis: Fungal (aspergillus, protozoal-Cerebritis: Fungal (aspergillus, protozoal-
toxoplasma)toxoplasma)
 Viral: CMV, VZV, PML, Aids encephalopathyViral: CMV, VZV, PML, Aids encephalopathy

Primary Tumors of the CentralPrimary Tumors of the Central
Nervous SystemNervous System
GliomaGlioma
AstrocytomaAstrocytoma
OligodendrogliomaOligodendroglioma
EpendymomaEpendymoma
 Neuronal lineageNeuronal lineage
 MeningiomaMeningioma
 Nerve Sheath TumorsNerve Sheath Tumors

Primary brain tumors: Cell typesPrimary brain tumors: Cell types
1.1. Neuron:Neuron: Gangliocytoma, gangliogliomaGangliocytoma, ganglioglioma
medulloblastomamedulloblastoma
2.2. AstrocyteAstrocyte:: Astrocytoma, glioblastomaAstrocytoma, glioblastoma
3.3. OligodendrocyteOligodendrocyte:: OligodendrogliomaOligodendroglioma
4.4. Ependymal cellEpendymal cell:: EpendymomaEpendymoma
5.5. Microglial cellMicroglial cell:: Tumors derived from microglialTumors derived from microglial
cells have not been described.cells have not been described.
6.6. Meningeal cellMeningeal cell:: Meningiomas are derived fromMeningiomas are derived from
arachnoidal cells and are usually dural-based.arachnoidal cells and are usually dural-based.

GLIOMASGLIOMAS
 ASTROCYTOMASASTROCYTOMAS
 OLIGODENDROGLIOMASOLIGODENDROGLIOMAS
 EPENDYMOMASEPENDYMOMAS
 MIXED GLIOMASMIXED GLIOMAS

GliomasGliomas
 Diffusely infiltrating (not easily resected)Diffusely infiltrating (not easily resected)
 Histologic appearance (grade) correlates withHistologic appearance (grade) correlates with
overall survivaloverall survival
 May become more malignant (higher grade) overMay become more malignant (higher grade) over
time (especially astrocytomas which becometime (especially astrocytomas which become
glioblastomas)glioblastomas)
 May spread via CSFMay spread via CSF
 Rarely (never) metastasizeRarely (never) metastasize

JUVENILE PILOCYTICJUVENILE PILOCYTIC
ASTROCYTOMAASTROCYTOMA

JUVENILE PILOCYTICJUVENILE PILOCYTIC
Rosenthal fibersRosenthal fibers Eosinophilic granularEosinophilic granular
bodiesbodies

FEATURES OF ANAPLASIAFEATURES OF ANAPLASIA
vascular proliferationvascular proliferation

GLIOBLASTOMAGLIOBLASTOMA
MULTIFORMEMULTIFORME

OLIGODENDROGLIOMAOLIGODENDROGLIOMA

Non-glial tumorsNon-glial tumors
 Medulloblastoma: Malignant cerebellar tumorMedulloblastoma: Malignant cerebellar tumor
of childhoodof childhood
 Meningioma: Benign, superficial, well-Meningioma: Benign, superficial, well-
circumscribed tumor derived from arachnoidalcircumscribed tumor derived from arachnoidal
cellscells
 Nerve sheath tumors: Schwannoma andNerve sheath tumors: Schwannoma and
neurofibroma, well-circumscribed, encapsulatedneurofibroma, well-circumscribed, encapsulated
tumors involving cranial nerves, spinal nervestumors involving cranial nerves, spinal nerves
and other peripheral nervesand other peripheral nerves

MEDULLOBLASTOMAMEDULLOBLASTOMA

Secondary Involvement of theSecondary Involvement of the
Central Nervous SystemCentral Nervous System
 Metastatic tumorMetastatic tumor
 MelanomaMelanoma
 Renal cellRenal cell
 LungLung
 Contiguous involvement (pituitaryContiguous involvement (pituitary
adenoma and craniopharyngioma)adenoma and craniopharyngioma)

METASTATIC TUMORSMETASTATIC TUMORS
leptomeningeal carcinomatosisleptomeningeal carcinomatosis

METASTATIC MELANOMAMETASTATIC MELANOMA

PRIMARY CNS LYMPHOMAPRIMARY CNS LYMPHOMA

Summary: Brain tumorsSummary: Brain tumors
 Primary brain tumors: glia (low grade vs. highPrimary brain tumors: glia (low grade vs. high
grade), neurons, meningesgrade), neurons, meninges
 Nerve sheath tumors: schwannoma andNerve sheath tumors: schwannoma and
neurofibromaneurofibroma
 Secondary brain tumors: Metastatic (lung-males,Secondary brain tumors: Metastatic (lung-males,
breast-females, melanoma, renal cell carcinoma)breast-females, melanoma, renal cell carcinoma)
 Tumors arising outside the CNS with CNSTumors arising outside the CNS with CNS
symptoms: pituitary adenoma,symptoms: pituitary adenoma,
craniopharyngiomacraniopharyngioma

DISEASES OF MYELINDISEASES OF MYELIN
AND PERIPHERALAND PERIPHERAL
NERVENERVE

MYELINMYELIN
PNS MYELINPNS MYELIN CNSCNS
MYELINMYELIN

CNS MYELINCNS MYELIN
oligodendrocytesoligodendrocytes

DISEASES OF MYELINDISEASES OF MYELIN
 DEMYELINATING DISEASES:DEMYELINATING DISEASES:
 Acquired disorders of myelin, such as multipleAcquired disorders of myelin, such as multiple
sclerosis.sclerosis.
 DYSMYELINATING DISEASES:DYSMYELINATING DISEASES:
 Genetic disorders of myelin and its turnover,Genetic disorders of myelin and its turnover,
such as leukodystrophiessuch as leukodystrophies

MULTIPLE SCLEROSISMULTIPLE SCLEROSIS
 Multiple sclerosis is the most common diseaseMultiple sclerosis is the most common disease
of CNS myelin; prevalence of 1:1000.of CNS myelin; prevalence of 1:1000.
 Central nervous system myelin is selectivelyCentral nervous system myelin is selectively
destroyed (axons are relatively preserved)destroyed (axons are relatively preserved)
 Onset is frequently in 30 and 40 year old ageOnset is frequently in 30 and 40 year old age
groups.groups.
 The disease is typically progressive with relapsingThe disease is typically progressive with relapsing
and remitting accumulations of focal neurologicand remitting accumulations of focal neurologic
deficits.deficits.
 The etiology is thought to be autoimmune inThe etiology is thought to be autoimmune in
naturenature

PLAQUESPLAQUES

PLAQUEPLAQUE

PLAQUESPLAQUES
optic chiasmoptic chiasm

PONTINE MS PLAQUEPONTINE MS PLAQUE
adjacent sections for myelin andadjacent sections for myelin and
axonsaxons
 Luxol fast-blue-PASLuxol fast-blue-PAS BielschowskyBielschowsky

MULTIPLE SCLEROSIS PLAQUEMULTIPLE SCLEROSIS PLAQUE
sharp circumscriptionsharp circumscription

ACUTE DISSEMINATEDACUTE DISSEMINATED
ENCEPHALOMYELITISENCEPHALOMYELITIS
 Post- or parainfectious encephalomyelitis:Post- or parainfectious encephalomyelitis:
 following a viral infectionfollowing a viral infection
 Postvaccinial encephalomyelitis:Postvaccinial encephalomyelitis:
 Pasteur rabies and smallpox vaccinationPasteur rabies and smallpox vaccination
 Akin to EAE (experimental allergic enceph.)Akin to EAE (experimental allergic enceph.)
 ADE is an acute, monophasic illnessADE is an acute, monophasic illness
 Pathology:Pathology:
 Perivenous lymphocytic infiltrates withPerivenous lymphocytic infiltrates with
demyelinationdemyelination
 Autoimmune mechanismAutoimmune mechanism

(ADEM)(ADEM)
H & EH & E Myelin basicMyelin basic
protein IHCprotein IHC

(ADEM)(ADEM)

Myasthenia GravisMyasthenia Gravis
 An autoimmune neuromuscular disease that resultsAn autoimmune neuromuscular disease that results
from autoantibodies at the neuromuscular junction.from autoantibodies at the neuromuscular junction.
 Characterized by variable weakness of voluntary muscles (eyeCharacterized by variable weakness of voluntary muscles (eye
muscles may be weak)muscles may be weak)
 Worsens with activity (and late in the day)Worsens with activity (and late in the day)
 May be associated with other autoimmune disordersMay be associated with other autoimmune disorders
such as thyroid disease, rheumatoid arthritis and SLEsuch as thyroid disease, rheumatoid arthritis and SLE
 Often associated with a thymoma, removal of theOften associated with a thymoma, removal of the
thymoma may be curative.thymoma may be curative.

LEUKODYSTROPHIESLEUKODYSTROPHIES
 CLINICAL: A variety of inherited diseases withCLINICAL: A variety of inherited diseases with
variable age of onset (usually in childhood) andvariable age of onset (usually in childhood) and
rate of progression, which typically result inrate of progression, which typically result in
diffuse severe dysfunction.diffuse severe dysfunction.
 PATHOGENESIS:PATHOGENESIS: Recessive mutations inRecessive mutations in
proteins related to myelin structure orproteins related to myelin structure or
metabolismmetabolism
 The peripheral nervous system also may beThe peripheral nervous system also may be
involved in a number of formsinvolved in a number of forms

PATHOLOGY OFPATHOLOGY OF
LEUKODYSTROPHIESLEUKODYSTROPHIES
 Demyelination in large confluent foci within the cerebralDemyelination in large confluent foci within the cerebral
hemispheres and other siteshemispheres and other sites
 GENERAL:GENERAL:
1.1. Loss of myelin and oligodendrogliaLoss of myelin and oligodendroglia
2.2. Relative preservation of axonsRelative preservation of axons
 DISEASE SPECIFIC:DISEASE SPECIFIC:
1.1. Globoid cells (Krabbe’s disease)Globoid cells (Krabbe’s disease)
2.2. Metachromatic material in macrophages and neuronsMetachromatic material in macrophages and neurons
(metachromatic leukodystrophy, aryl sulfatase deficient)(metachromatic leukodystrophy, aryl sulfatase deficient)
3.3. Adrenal atrophy and cytosomal inclusions (ALD,Adrenal atrophy and cytosomal inclusions (ALD,
peroxisomal abnormality)peroxisomal abnormality)

METACHROMATICMETACHROMATIC
LEUKODYSTROPHYLEUKODYSTROPHY

sparing of subcortical arcuate fiberssparing of subcortical arcuate fibers

(aryl sulfatase deficiency)(aryl sulfatase deficiency)
Acidified cresyl violetAcidified cresyl violet LFB-PASLFB-PAS
metachromasiametachromasia

ADRENOLEUKODYSTROPHYADRENOLEUKODYSTROPHY

ADRENOLEUKODYSTROPHYADRENOLEUKODYSTROPHY
lymphocytic infiltrateslymphocytic infiltrates

KRABBE’S DISEASEKRABBE’S DISEASE
(GLOBOID CELL(GLOBOID CELL
LEUKODYSTROPHY)LEUKODYSTROPHY)
cerebroside-cerebroside-ββ-galactosidase deficiency-galactosidase deficiency

DISEASES OF PERIPHERALDISEASES OF PERIPHERAL
NERVENERVE
CLASSIFICATION BY PATHOLOGYCLASSIFICATION BY PATHOLOGY
Demyelinating neuropathiesDemyelinating neuropathies
Guillain-Barre-Landry syndromeGuillain-Barre-Landry syndrome
Chronic inflammatory demyelinating polyneuropathyChronic inflammatory demyelinating polyneuropathy
(CIDP)(CIDP)
Axonal neuropathies: most neuropathies areAxonal neuropathies: most neuropathies are
axonal but pathology often is nonspecificaxonal but pathology often is nonspecific
Examples include hypertrophic neuropathies,Examples include hypertrophic neuropathies,
herpes zoster, HIV, alcoholic and diabeticherpes zoster, HIV, alcoholic and diabetic
neuropathiesneuropathies

DEMYELINATING NEUROPATHYDEMYELINATING NEUROPATHY
GUILLAIN-BARRE-LANDRYGUILLAIN-BARRE-LANDRY
LFB-PASLFB-PAS Silver stainSilver stain

DEMYELINATING NEUROPATHYDEMYELINATING NEUROPATHY
inflammatory demyelinationinflammatory demyelination

DEMYELINATINGDEMYELINATING
NEUROPATHYNEUROPATHY
evidence of remyelinationevidence of remyelination

Summary:Summary:
Demyelinating/DysmyelinatingDemyelinating/Dysmyelinating
diseasesdiseases
 Demyelinating disease: most common is MS,Demyelinating disease: most common is MS,
acute disseminated encephalomyelitis (rare,acute disseminated encephalomyelitis (rare,
follows viral infection, vaccination)follows viral infection, vaccination)
 Leukodystrophies: Genetic diseases (manyLeukodystrophies: Genetic diseases (many
enzyme abnormalities are defined) resulting inenzyme abnormalities are defined) resulting in
myelin loss, occur early in life.myelin loss, occur early in life.
 Peripheral nerve demyelination: Guillain-BarrePeripheral nerve demyelination: Guillain-Barre
Syndrome, autoimmune, potential forSyndrome, autoimmune, potential for
remyelination with complete recoveryremyelination with complete recovery

NeurodegenerativeNeurodegenerative
diseasesdiseases
Dementia:Dementia:
Alzheimer’s disease, Pick’s diseaseAlzheimer’s disease, Pick’s disease
Movement Disorders:Movement Disorders:
Parkinson’s disease, Huntington’sParkinson’s disease, Huntington’s
disease, Multiple Systems Atrophydisease, Multiple Systems Atrophy
Motor Disease:Motor Disease:
ALS, Werdnig-Hoffman, PoliomyelitisALS, Werdnig-Hoffman, Poliomyelitis
Prion diseasePrion disease

Alzheimer’s disease: ClinicalAlzheimer’s disease: Clinical
featuresfeatures
 Clinical features of dementiaClinical features of dementia
 Impairment of recent memoryImpairment of recent memory
 Aphasia (naming), apraxia (motor), agnosiaAphasia (naming), apraxia (motor), agnosia
(object), executive functioning(object), executive functioning
 Impaired level of functionImpaired level of function
 Progressive over timeProgressive over time
 47% of people over 85 years of age are47% of people over 85 years of age are
affectedaffected

Alzheimer’s disease: PathogenesisAlzheimer’s disease: Pathogenesis
 The amyloid hypothesis:The amyloid hypothesis:
Abnormal APP processingAbnormal APP processing
leads to deposits ofleads to deposits of
insoluble B-pleatedinsoluble B-pleated
amyloid proteinamyloid protein

Alzheimer’s disease: Gross andAlzheimer’s disease: Gross and
microscopic featuresmicroscopic features
 Gross brain atrophy: neuronal lossGross brain atrophy: neuronal loss
 Neuritic (senile) plaquesNeuritic (senile) plaques containingcontaining B-B-
amyloidamyloid
 Neurofibrillary tanglesNeurofibrillary tangles composed ofcomposed of
phosphorylated microtubule associatedphosphorylated microtubule associated tautau
proteinprotein
 Cerebral amyloidosisCerebral amyloidosis

Other DementiasOther Dementias
 Dementia with Lewy bodiesDementia with Lewy bodies
 Second most common neurodegenerative cause ofSecond most common neurodegenerative cause of
dementiadementia
 Lewy bodies and neurodegeneration affect brainstemLewy bodies and neurodegeneration affect brainstem
and cortexand cortex
 Pick’s disease and other frontal temporalPick’s disease and other frontal temporal
dementiasdementias
 Classification depends on histologic examination andClassification depends on histologic examination and
is complicatedis complicated

Parkinson’s disease: ClinicalParkinson’s disease: Clinical
findingsfindings
 Idiopathic Parkinson’s disease (vs.Idiopathic Parkinson’s disease (vs.
parkinsonism or parkinsonian syndrome),parkinsonism or parkinsonian syndrome),
est 1% of population over 50 years of ageest 1% of population over 50 years of age
 TremorTremor (rest)(rest)
 RigidityRigidity (cogwheel rigidity)(cogwheel rigidity)
 BradykinesiaBradykinesia (mask-like facies, loss of arm-(mask-like facies, loss of arm-
swing)swing)
 Festinating gait (loss of righting reflexes)Festinating gait (loss of righting reflexes)

Parkinson’s disease: Gross andParkinson’s disease: Gross and
microscopic findingsmicroscopic findings
 Gross--Gross--loss of pigmentloss of pigment in thein the substantiasubstantia
nigranigra
 Microscopic--Lewy bodies with pigmentedMicroscopic--Lewy bodies with pigmented
neuronal cell loss and gliosisneuronal cell loss and gliosis
 cortical Lewy bodies present in 80% or morecortical Lewy bodies present in 80% or more
of PD casesof PD cases

Other Extrapyramidal MovementOther Extrapyramidal Movement
DisordersDisorders
 Parkinson’s disease: HypokineticParkinson’s disease: Hypokinetic
 Huntington’s disease: HyperkineticHuntington’s disease: Hyperkinetic
 Choreiform movementsChoreiform movements
 Intellectual declineIntellectual decline
 Multiple Systems AtrophyMultiple Systems Atrophy
 Parkinsonian featuresParkinsonian features
 Symptoms suggestive of olivopontocerebellarSymptoms suggestive of olivopontocerebellar
degenerationdegeneration
 Shy-Drager syndrome (parasympathetic dysfunction)Shy-Drager syndrome (parasympathetic dysfunction)

Motor neuron diseaseMotor neuron disease
 Amyotrophic lateral sclerosis (Lou Gehrig’sAmyotrophic lateral sclerosis (Lou Gehrig’s
disease)disease)
 Results in progressive weakness, eventually resultingResults in progressive weakness, eventually resulting
in paralysis of respiratory muscles and death oftenin paralysis of respiratory muscles and death often
within 2-5 years of diagnosiswithin 2-5 years of diagnosis
 Degeneration of upper (motor cortex) and lowerDegeneration of upper (motor cortex) and lower
(spinal cord) motor neurons(spinal cord) motor neurons

Motor Neuron DiseaseMotor Neuron Disease
 ALS: Adult form of motor neuron diseaseALS: Adult form of motor neuron disease
associated with both upper (brain) and lowerassociated with both upper (brain) and lower
(spinal cord) motor involvement(spinal cord) motor involvement
 Werdnig-Hoffman disease: The baby is weakWerdnig-Hoffman disease: The baby is weak
(floppy) at birth. Lower (spinal cord) motor(floppy) at birth. Lower (spinal cord) motor
neurons are involved.neurons are involved.
 Poliomyelitis: Lower motor neurons arePoliomyelitis: Lower motor neurons are
destroyed.destroyed.

Prion disease (SpongiformPrion disease (Spongiform
encephalopathy): Clinical findingsencephalopathy): Clinical findings
 50-70 years old,50-70 years old, rapidly evolving dementiarapidly evolving dementia,,
often withoften with myoclonusmyoclonus and a characteristic EEGand a characteristic EEG
pattern (of repetitive sharp waves)pattern (of repetitive sharp waves)
 Early symptoms include personality changes,Early symptoms include personality changes,
impaired judgement, gait abnormalities, vertigo,impaired judgement, gait abnormalities, vertigo,
 In some patients cerebellar and visualIn some patients cerebellar and visual
abnormalities predominateabnormalities predominate
 MajorityMajority die w/in 6 monthsdie w/in 6 months, frequently w/in 3, frequently w/in 3
mo.mo.

Prion disease: PathogenesisPrion disease: Pathogenesis
 Transmissible but not “infectious”Transmissible but not “infectious”
 Prion proteinPrion protein, Prusiner--1997 Nobel Prize, (not a, Prusiner--1997 Nobel Prize, (not a
“slow virus”)“slow virus”)
 PrPPrPCC
-- produced normally in most cells --amino acid-- produced normally in most cells --amino acid
sequence is identical to the PrPsequence is identical to the PrPSCSC
--abnormal protein, the--abnormal protein, the
difference is in the secondary conformation (B-pleateddifference is in the secondary conformation (B-pleated
vs alpha helical) PrPvs alpha helical) PrPSCSC
causes post-translationalcauses post-translational
modification of PrPmodification of PrPCC
 Transmitted by direct inoculation (corneal transplants,Transmitted by direct inoculation (corneal transplants,
dural grafts, pituitary products)dural grafts, pituitary products)

Prion disease: Gross andPrion disease: Gross and
microscopic findingsmicroscopic findings
 Gross appearance--may be normal due toGross appearance--may be normal due to
short duration of diseaseshort duration of disease
 Microscopic appearance--vacuolation ofMicroscopic appearance--vacuolation of
neuropil, vacuoles are within nerve cellneuropil, vacuoles are within nerve cell
bodies and neuronal processesbodies and neuronal processes
 cell loss and gliosis may be prominentcell loss and gliosis may be prominent

Summary: NeurodegenerativeSummary: Neurodegenerative
diseasesdiseases
 DementiaDementia
 Alzheimer’s disease: common, amyloid hypothesis, plaquesAlzheimer’s disease: common, amyloid hypothesis, plaques
and tangles, gross brain atrophyand tangles, gross brain atrophy
 Prion disease: rare, “transmissible” protein, rapidlyPrion disease: rare, “transmissible” protein, rapidly
progressive, vacuolar changesprogressive, vacuolar changes
 Movement disordersMovement disorders
 Parkinson’s disease: hypokinetic, loss of dopaminergic cellsParkinson’s disease: hypokinetic, loss of dopaminergic cells
substantia nigra, Lewy bodiessubstantia nigra, Lewy bodies
 Huntington’s disease: choreiform movements, caudateHuntington’s disease: choreiform movements, caudate
atrophy, nuclear inclusionsatrophy, nuclear inclusions
 Motor neuron disease (ALS): Loss of upper and lowerMotor neuron disease (ALS): Loss of upper and lower
motor neurons, progressive over 2-5 yearsmotor neurons, progressive over 2-5 years

PediatricPediatric
NeuropathologyNeuropathology
Developmental AbnormalitiesDevelopmental Abnormalities
Neuronal Storage DiseasesNeuronal Storage Diseases
Familial Tumor SyndromesFamilial Tumor Syndromes
Perinatal Lesions/InfectionsPerinatal Lesions/Infections
Trauma: shaken baby syndromeTrauma: shaken baby syndrome

Developmental Abnormalities:Developmental Abnormalities:
PathologyPathology
 Organ inductionOrgan induction (2.5-6 weeks): neural tube defects:(2.5-6 weeks): neural tube defects:
anencephaly, spinal dysraphism, encephalocele,anencephaly, spinal dysraphism, encephalocele,
holoprosencephalyholoprosencephaly
 Neuronal (glial) migrationNeuronal (glial) migration (3-6 months):(3-6 months):
lissencephaly, microcephaly, polymicrogyria, agenesis oflissencephaly, microcephaly, polymicrogyria, agenesis of
the corpus callosumthe corpus callosum
 MyelinationMyelination (2 months-juvenile)(2 months-juvenile)
 SynaptogenesisSynaptogenesis (20 week gestation-adulthood):(20 week gestation-adulthood):
trisomy 21, fragile X, cretinismtrisomy 21, fragile X, cretinism
In general,In general, earlier insults cause more severe structuralearlier insults cause more severe structural
damagedamage

Organ Induction:Organ Induction:
Dysraphic DisordersDysraphic Disorders
 Failure of neural tube folds to close duringFailure of neural tube folds to close during
developmentdevelopment
 Prenatal testing may reveal an elevated maternal serumPrenatal testing may reveal an elevated maternal serum
AFPAFP
 Folate deficiency: Folic acid supplementation prior toFolate deficiency: Folic acid supplementation prior to
conception may reduce the incidence of neural tubeconception may reduce the incidence of neural tube
defects up to 70%defects up to 70%
 Neural tube defects range from small bony defects in theNeural tube defects range from small bony defects in the
lumbosacral region (spina bifida occulta) tolumbosacral region (spina bifida occulta) to
craniorachischisis.craniorachischisis.
 Myelomeningoceles occur most commonly in theMyelomeningoceles occur most commonly in the
lumbosacral regionlumbosacral region

Neuronal migration disordersNeuronal migration disorders
 Lissencephaly (smooth brain)/pachygyria (fewLissencephaly (smooth brain)/pachygyria (few
enlarged gyrienlarged gyri
 Polymicrogyria (many small gyri)Polymicrogyria (many small gyri)
 Heterotopias (circumscribed collections) andHeterotopias (circumscribed collections) and
dysplasias (disorganized lamination)dysplasias (disorganized lamination)
 Occur with other developmental abnormalities forOccur with other developmental abnormalities for
example in patients with chromosomal abnormalitiesexample in patients with chromosomal abnormalities
 May be the focus of seizure activityMay be the focus of seizure activity

SeizuresSeizures
 Result from abnormal electrical activity of a group ofResult from abnormal electrical activity of a group of
brain cells and cause an altered mental state or tonicbrain cells and cause an altered mental state or tonic
clonic movements. May be partial (focal) orclonic movements. May be partial (focal) or
generalized.generalized.
 In children seizures may result from neuronal migrationIn children seizures may result from neuronal migration
abnormalities or from abnormalities acquiredabnormalities or from abnormalities acquired
subsequent to brain damage (such as inflammation)subsequent to brain damage (such as inflammation)
 A first time seizure in an adult would warrant anA first time seizure in an adult would warrant an
imaging study to rule out tumor or other structuralimaging study to rule out tumor or other structural
abnormalityabnormality

Neuronal Storage DiseaseNeuronal Storage Disease
 Result from inborn errors of metabolism (deficientResult from inborn errors of metabolism (deficient
enzyme or abnormal lysosomal function)enzyme or abnormal lysosomal function)
 Progressive, poor treatment options (bone marrowProgressive, poor treatment options (bone marrow
transplant)transplant)
 Accumulation of metabolic products in the neuronAccumulation of metabolic products in the neuron
 Tay Sachs diseaseTay Sachs disease
 Neuronal ceroid lipofuscinosisNeuronal ceroid lipofuscinosis
 Glycogen storage diseaseGlycogen storage disease

Concentric Multilamellar membranous cytoplasmic bodies (MCB’s)

Familial Tumor SyndromesFamilial Tumor Syndromes
 NeurofibromatosisNeurofibromatosis
 NF-1: (most common) multiple peripheral neurofibromasNF-1: (most common) multiple peripheral neurofibromas
 NF-2: bilateral acoustic schwannomas and meningiomasNF-2: bilateral acoustic schwannomas and meningiomas
 Tuberous Sclerosis: subcortical and corticalTuberous Sclerosis: subcortical and cortical
hamaratomas(tubers)hamaratomas(tubers)
-Autosomal dominant-Autosomal dominant
-Tumor suppressor gene mutations-Tumor suppressor gene mutations
-Cutaneous findings-Cutaneous findings

Perinatal Lesions ofPerinatal Lesions of
the CNSthe CNS
Hypoxic/IschemicHypoxic/Ischemic
InfectiousInfectious

Congenital/Perinatal InfectionsCongenital/Perinatal Infections
TORCHTORCH
 ToxoplasmosisToxoplasmosis
 Other: syphilis, TB, listeria monocytogenes;Other: syphilis, TB, listeria monocytogenes;
other viruses (VZV, HepB)other viruses (VZV, HepB)
 Rubella (rare—immunizations)Rubella (rare—immunizations)
 Cytomegalovirus, Chlamydia trachomatisCytomegalovirus, Chlamydia trachomatis
 Herpes simplex (usually type 2); HIVHerpes simplex (usually type 2); HIV

Shaken Baby SyndromeShaken Baby Syndrome
 General: Violent shaking causes accelerationGeneral: Violent shaking causes acceleration
((shearingshearing) injury of axons:) injury of axons: diffuse axonal injurydiffuse axonal injury
 Neurologic: Blindness/mental retardation in infantsNeurologic: Blindness/mental retardation in infants
less than 1 year of age. Present with apnea, seizures,less than 1 year of age. Present with apnea, seizures,
lethargy, bradycardia, respiratory difficulty, coma.lethargy, bradycardia, respiratory difficulty, coma.
 Pathology:Pathology: Oculo-cerebral damage can occurOculo-cerebral damage can occur
without external evidence of head injury.without external evidence of head injury. RetinalRetinal
and optic nerve sheath hemorrhage—and optic nerve sheath hemorrhage—
ophthalmoscopic exam importantophthalmoscopic exam important
 Microscopic: Axonal spheroidsMicroscopic: Axonal spheroids

Summary: Pediatric neuropathologySummary: Pediatric neuropathology
 Developmental abnormalities: Neural tubeDevelopmental abnormalities: Neural tube
defects (anencephaly, spina bifida), migrationaldefects (anencephaly, spina bifida), migrational
defects (mental retardation, seizures)defects (mental retardation, seizures)
 Inborn errors of metabolism: Neuronal storageInborn errors of metabolism: Neuronal storage
diseases and leukodystrophiesdiseases and leukodystrophies
 Other: Familial tumor syndromes, hemorrhage,Other: Familial tumor syndromes, hemorrhage,
hypoxic/ischemic injury, shaken baby syndromehypoxic/ischemic injury, shaken baby syndrome

The more people IThe more people I
meet…meet…
The more I likeThe more I like
my dogmy dog

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