Patologi Sistem Saraf.edit

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PATHOLOGY OF CENTRAL NERVOUS

SYSTEM

Yekti W. Widjono


Central Nervous System

CONGENITAL

INFECTION

NEOPLASM

CEREBROVASCULAR

TRAUMA
























PRINTED BY FILAMEN '05Focal polymicrogyria: An incidental finding in a neurologically normal, 86-year-old man who died of chronic lung disease












CNS Infections: Routes

1. Direct - skull fracture

2. Extension - sinuses and ears

3. Blood dissemination

4. Peripheral nerves (viruses)


Some definitions

Pachymeningitis: inflammation of dura

Leptomeningitis (meningitis): infl of arachnoid

Cerebritis: infection of brain parenchyma by

agents other than viruses

Encephalitis: infl of parenchyma by viruses


Acute meningitis: pathology

Bacterial: infiltration by neutrophils

Viral (aseptic): infiltration by lymphocytes

Fungus: predominantly infiltration by lymphocytes

Infiltration more common at base of brain than at

convexity





Acute purulent meningitis: causative organisms

Neonatal: E. coli, B. strepto, L. monocytogenes

Children: H. influenzae, S. pneumoniae

Adolescents: N. meningitidis (meningococcus)

Adults: S. pneumoniae


Acute bacterial meningitis: complications

Hydrocephalus, if not resolved

Pyocephalus (pus in ventricle)

Thrombosis of meningeal vessels and infarcts

Cerebritis and abscess


Aseptic meningitis

Resolves spontaneously

No permanent sequela

Viruses:

Mumps, coxsackie, echo


Chronic meningitis: pathology

Organisms: mycobacteria, fungus, spirochettes

Infiltration by lymphocytes

Granulomas: tuberculosis, fungus

Complications

fibrosis at base of brain hydrocephalus (more common than in bacterial

infection) Resolves spontaneously



Aspergillosis

1. Opportunistic infection

2. Primary pulmonary infection

3. Cerebritis, abscess, infarctions

4. Vascular invasion


Candidosis

1. Opportunistic infection

2. Primary GI infection

3. Microabscesses

4. Most common CNS fungal

infection at autopsy


Cryptococcosis

1. Most common clinical CNS mycosis

2. Primary lung infection

3. Majority spontaneous infection

4. 30% opportunistic infections

5. Minimal inflammation

6. Multiple cysts: honey-comb appearance

7. India-ink exam of CSF


Phycomycosis

1. Mucormycosis common

2. Associated with:

Diabetic ketoacidosis

Intravenous drug abuse

3. Acute fulminant disorder


Bacterial Parenchymal Infections

Cerebritis

Brain abscess


Brain Abscess: Sites

1. Direct extension:– large; single– frontal lobe in frontal sinusutis– temporal lobe in otitis and mastoiditis

2. Embolic:

small; multiple

MCA territory common


Cerebral Abscess:Pathology

1. Suppurative cerebritis

2. Abscess formation

3. Granulation tissue

4. Fibrous capsule




Encephalitis: Viral Tropism

1. Coxsackie, Echo, Mumps: Meninges

2. Herpes simplex: Temporal lobes

3. Herpes zoster (varicella): Posterior

ganglia

4. Poliomyelitis: Motor neurons

5. Rabies: Hippocampus, cerebellum

6. JC virus (PML): Oligodendrocytes


Acute viral encephalitis: Pathology

Lymphocytic infiltration

Perivascular lymphocytes

Microglial nodules

Inclusion body

Necrosis



Viral inclusion bodies: sites

HSV: intranuclear in neurons and oligodendrocytes

Rabies: intracytoplasmic in neurons

Cytomegalovirus: intranuclear or intracytoplasmic in neurons, glial cells, ependyma

PML: intranuclear in oligodendrocytes


Slow Virus Infections: TypesConventional viruses:

1. Progressive multifocal leukoencephalopathy (PML)

PAPOVA viruses

2. Subacute sclerosing panencephalitis (SSPE)Measles virus

3. Progressive rubella encephalopathyRubella virus

Unconventional agents:Spongiform Encephalopathies (PRION

diseases)


Pathologic States Associated with Progressive

Multifocal Leukoencephalopathy

Lymphoma

Leukemia

Sarcoidosis

Carcinomatosis

Miliary tuberculosis

Organ transplants (kidney)

AIDS


Transmissible Spongiform Encephalopathies (PRION diseases)

Animals:

Scrapie - sheep, goat

Transmissible mink encephalopathy

Chronic wasting disease - mule deer, elk

Feline spongiform encephalopathy

Bovine spongiform encephalopathy (BSE)

Humans (subacute spongiform encephalopathy):

Kuru

Creutzfeldt-Jacob disease (CJD)

Gerstmann-Straussler Syndrome - Fam AD

Fatal familial insomnia - Fam AD


Please read from the book on:

HIV infection (AIDS)

Cytomegalovirus

Toxoplasmosis


BRAIN NEOPLASM


General Considerations1. Comprise: 10% of all tumors

2. Most common childhood neoplasms

3. Peak incidence at 5th decade

4. Supratentorial tumors in adults

5. Infratentorial tumors in childhood

6. Different tumors in different ages

7. Primary tumors – infiltrative Metastatic - well-demarcated

8. Intraneural seeding occur, but no extraneural metastasis

9. Produce neurologic symptoms by size,location,invasiveness, and secondary effects


Varieties of brain tumors

Meninges: meningioma, hemangiopericytoma

Astrocytes: astrocytoma (various types)

Oligodendrocytes: oligodendroglioma

Ventricles: ependymoma, choroid plexus papilloma,

colloid cyst

Vascular: hemangioblastoma

Primitive cells: germinoma, medulloblastoma,

neuroblastoma, pineoblastoma, retinoblastoma

Neuronal: ganglioglioma, gangliocytoma

Pituitary: adenoma, craniopharyngioma

Nerves: schwannoma, neuroblastoma


Astrocytes: astrocytoma (various types)

Oligodendrocytes: oligodendroglioma

Ventricles: ependymoma, choroid plexus

papilloma, colloid cyst

GLIOMA


Incidence of Intracranial Gliomas (All ages)

Glioblastomas

Astrocytomas

Ependymomas

Medulloblastomas

Oligodendrogliomas

Choroid plexus papillomas

Colloid cysts

55.0%

20.5%

6.0%

6.0%

5.0%

2.0%

2.0%


Incidence of Primary IntraspinalIntramedullary Gliomas

Ependymomas

Astrocytomas (grades 1 and 2)

Glioblastomas (Astrocytomas

grades 3 and 4)

Oligodendrogliomas

Other tumors

63.0%

24.5%

7.5%

3.0%

2.0%


Frequent Brain Tumors

Meningioma

Astrocytoma/glioblastoma

Oligodendroglioma

Ependymoma

Medulloblastoma

Schwannoma/neurofibroma

Phakomatosis


Meningioma

Arachnoid cells origin

Attached to dura, subdural

Common sites: parasagittal (falx),

sphenoidridge, olfactory groove

Female:Male 3:2 or 2:1

Changes in cranium

Hyperostosis

Invasion

Microscopic: whorls and psammoma bodies



Menoingioma


Meningothelail whorls


Psammoma bodies


Gliomas

Astrocytes- astrocytomas

Fibrillary

Pilocytic

Oligodendrocytes- oligodendrogliomas

Ependyma- ependymomas


Astrocytomas

Adult

Supratentorial

Solid

Malignant

Fibrillary

Childhood

Infratentorial

Cystic

Benign

Pilocytic


Fibrillary Astrocytomas

Grossly solid

Common in cerebral hemispheres

Low grade in young, higher

grade in older

Grading

Astrocytoma (low grade)

Anaplastic astocytoma

Glioblastoma multiforme



Fibrillary Astrocytoma: microscopic

Low grade- hypercellularity, pleomorphism

Anaplastic- as above plus mitosis, vascular

endothelial proliferation

Glioblastoma multiforme- as above plus

necrosis and pseudopalisades. Grossly

variegated appearance (multiforme)


Astrocytoma


Glioblastoma


Glioblastoma - pseudopalisade


Pilocytic AstrocytomaCommon in childhood

Most slow growing of the gliomas

Sites: cerebellum, around III V., optic

nerve

Grossly cystic with mural nodule

Microscopic

Elongated hair-like (pilo) elongated

cells

Rosenthal fibers


Rosenthal fiber definition

Dense, eosinophilic fibers within

cytoplasmic processes of astrocytes.

Correspond to aggregate accumulation of

intermediate filaments in these processes.


Pilocytic astrocytomaMural nodule


Pilocytic astrocytoma


Oligodendroglioma

Cells of origin: Oligodendrocytes

Common in cerebral hemispheres

Calcifications common among all

gliomas

Grades

Low grade

Anaplastic


Oligodendroglioma


Oligodendroglioma, calcifications


Tumors in Ventricles

1. Ependyma: Ependymoma

2. Choroid Plexus: Papilloma


Ependymomas

Arise from ependymal lining- ventricles

and central canal of spinal cord

Common in childhood

4th V. common in cerebrum

Most common tumor of spinal cord

parenchyma in adult

Microscopic

perivascular pseudorosettes

ependymal rosettes


Ependymoma


Ependymoma: perivascular pseudorosettes


Embryonal tumors(Primitive neuroectodermal tumors)

Neuroblastoma - cerebral hemispheres

Neuroblastic (neuronal) differentiation

Medulloblastoma - cerebellum

Neuronal and glial differentiation

Ependymoblastoma – ventricles

Ependymal differentiation

Pineoblastoma- pineal region

Retinoblastic differentiation

All commonly known as Primitive

neuroectodermal tumor (PNET)


Medulloblastoma

Origin: primitive neuroectodermal cells

Age: 1st decade of life. Most common

brain tumor at this age.

Site: vermis of cerebellum

May cause hydrocephalus

Subarachnoid dissemination


Medulloblastoma


Homer-Wright rosettes


Histologic Patterns: definitions

Whorls: onion-skinning pattern of tumor cells

Psammoma bodies: laminated calcium

Pseudopalisading: lining up of the tumor cells

around a central necrotic area

Palisade: lining up of tumor cells around their own

cytoplasmic processes. No necrosis.

Pseudorosette: tumor cells around blood vessels,

cells equidistant from vessel walls.

Rosettes: tumor cells around central lumen or

fibrillary area of cellular processes


Brain Tumors: Microscopic

Tumor Microscopic

Meningioma Whorls and psammoma bodies

Glioblastoma Pseudopalisades

Oligodendroglioma Mosaic/poached-egg

Ependymoma Perivascular pseudorosettes

Medulloblastoma Rosettes (Homer-Wright)


Tumors of Nerve Rootsand Peripheral Nerves

1. Schwannoma

viii Cranial nerve (Acoustic sch.)

Spinal roots, posterior

Peripheral nerves

2. Neurofibroma

Spinal Roots, rare

Peripheral nerves

3. Malignant variants

Malignant peripheral nerve sheath tumor (MPNT)

Rare


Peripheral nerve tumors

Schwannoma

Schwann cells

Compress the nerve trunk

Encapsulated

Easily resectable without nerve damage

Microscopic:

Antony A and B fibers

Verocay bodies

Neurofibroma

Schwann cells, neurites, fibroblasts

Fusiform and involves nerve trunk

Not encapsulated

Not resectable without sacrificing nerve

Micro- Intermingled cells with wavy nuclei


AcousticSchwannoma


Antony A

Antony B

Palisades


Metastatic Brain TumorsMost common brain tumor in adults.

Common primary sites: melanoma, lung,

breast, GI tract, kidney.

Most are in cerebrum (MCA territory).

In gray-white junctions due to rich capillarity

Discrete, globoid, sharply demarcated tumors.

Amenable to surgical resection.

Single or multiple.

Brain edema frequent.


Metastatic tumors


Phakomatosis : definition

Phakos (Greek): lentil mole or freckle.

Neurologic abnormalities combined with

defects of skin or retina, explained by their

common ectodermal origin.

Involvement of visceral organs


Phakomatosis(Neurocutaneous dysplasia)

1. Neurofibromatosis

(von Recklinghausen's dis.)

2. Tuberous Sclerosis

3. Sturge-Weber disease

(Encephalofacial Angiomatosis)

4. von Hippel-Lindau Disease

5. Neurocutaneous Melanosis


Neurofibromatosis

1. Dominant inheritance

2. Multiple neurofibromas

Central - CNS

Peripheral nerves

3. Increased incidence of:

Meningioma

Glioma

Schwannoma - bilateral VIII N.

4. Cafe-au-lait (melanosis) in skin

5. Elephantiasis: increased connective

tissue


Multiple neurofibromasCafé-au-lait spots


Tuberous Sclerosis

1. Dominant inheritance

2. Clinical triad:– Seizures– mental retardation– adenoma sebaceum

3. Retinal hamartoma (phakoma)

4. Tubers in cerebral cortex

5. Subependymal giant cell astrocytoma

6. Hamartomas in other organs: heart, kidney


Tubers


Adenoma sebaceum


CEREBROVASCULAR DISORDERS


Cerebrovascular diseases involve circulatory disorders of brain secondary to alterations of structural integrity of blood vessels and/or alterations of blood pressure, and the complications thereof

Cerebrovascular disease is the third leading cause of death after heart disease and cancer in developed world.


Some DefinitionsAnoxia - lack of oxygen

Ischemia - lack of circulation

Intracranial - enclosed by cranial bone (dura, arachnoid, brain)

Intracranial arteries - branches of circle of Willis in subarachnoid space (vertebro-basilar, ICA, MCA, ACA)

Intracerebral arteries/arterioles - within brain parenchyma

Intramedullary - in medulla or spinal cord


Major Types of Cerebrovascular Disease

1. Anoxia/Ischemia

2. Intracranial hemorrhage


Generalized (global)To entire brain

Focal (occlusive disease)To portion of brain

Ischemia



Sequelae of severe global ischemia

Persistent vegetative state

severe neurological impairment and deep coma

Brain death

absence of perfusion, reflexes, respiration

brain stem damage

isoelectric (flat) EEG

“respirator brain”


Conditions associated with hypotension

Myocardial infarction

Septic shock

GI hemorrhage

ruptured varices

bleeding ulcer

Ruptured aortic aneurysm

Others


Arterial

Occlusio

n: Caus

es

1. Atherosclerosis

2. Thrombosis

3. Embolism

4. Vasospasm

5. Extrinsic compression

Anemic infarction

Hemorrhagic infarction


Anemic and hemorrhagic infarctions vs hemorrhage

Anemic (pale, ischemic) infarction

no hemorrhage in infarcted area

Hemorrhagic infarction

petechial hemorrhage in infarcted area

no displacement of brain tissue

Hemorrhage

Bleeding is the primary event. Destroys and displaces the brain tissue


Embolic Materials

1. Thrombus: from heart; aorta; carotid

2. Atheroma: aorta; carotid

3. Septic: endocarditis

Note: Most emboli go to middle cerebral artery.


Intracranial Hemorrhage: Sites and Causes

1. Epidural

2. Subdural

3. Intracerebral

4. Subarachnoid

5. Mixed cerebral-subarachnoid

Trauma

Vascular (and trauma)


1. Intracerebral

Hypertension

2. Subarachnoid

Berry aneurysm

3. Mixed cerebral-subarachnoid

Vascular malformations

Intracranial Hemorrhage: Main Causes


Hypertensive Brain Hemorrhage: Sites

1. Putamen-Claustrum

2. Cerebral white matter

3. Thalamus

4. Pons

5. Cerebellum

55%

15

10

10

10




Hypertensive Hemorrhage: Clinical

Presence of hypertension

Absence of prodroms

Headache frequent

Gradual or abrupt neurologic deficit

Deepening stupor or coma

Blood CSF (blood ruptures in ventricle or subarachnoid space)


Intracranial vs intracerebral arteries

Intracranial arteries – atherosclerosis

Intracerebral arteries - hypertensive disease. No atherosclerosis.


Vascular changes in hypertension

Accelerated atherogenesis in arteries

changes in arteriolesthickening and hyalinization of wall (arteriolosclerosis or arteriolar sclerosis)



Vascular changes in hypertension

Accelerated atherogenesis in arteries

changes in arteriolesthickening and hyalinization of wall (arteriolosclerosis or arteriolar sclerosis)

necrosis of vessel wall (fibrinoid necrosis)




1. Ruptured saccular (berry) aneurysm

2. Vascular malformations

3. Mycotic aneurysm (septic emboli)

4. Trauma

Causes of Subarachnoid Hemorrhage


An aneurysm is

a dilatation of wall of an artery,

a vein or the heart.


Aneurysms- Types

Saccular (berry)

Atherosclerotic (fusiform)

Mycotic (infections)

Dissecting (rare)


Berry aneurysm Occur only at circle of Willis

Arise at points of branching

Saccular structure (sac-like, berry)

Devoid of media and elastic lamina

Multiple aneurysms common

Common sites: middle cerebral, internal carotid, anterior cerebral arteries

Most common cause of non-traumatic bleeding in the subarachnoid space

Increased incidence in patients with: inherited polycyctic kidney; neurofibromatosis; Marfan syndrome; fibromuscular dysplasia; coarction of aorta.




Ruptured Aneurysm: Clinical

Sudden severe headache

Relative alertness following initial unconsciousness

No focal neurologic deficit

Bloody CSF


Vascular Malformations of brain: Types

1. Arteriovenous malformation (AVM)

2. Cavernous angioma

3. Venous angioma

4. Capillary telangiectasis


Arteriovenous malformation (AVM)

1. Abnormal thick arteries and veins

2. No intervening capillary channels

3. Arterio-venous fistula

4. Occur any part of the brain fromsurface to ventricle

5. Common type of malformationand cause of hemorrhage





Cavernous (hem)angioma

1. Dilated veins

2. Veins intercommunicate

3. No brain tissue between the veins

4. Common type of malformationand cause of hemorrhage


Venous (hem)angioma

1. Dilated veins

2. Do not communicate

3. Brain tissue present in between vessels

4. Not a common source of bleeding



Capillary telangiectasis1. Dilated capillaries

2. Not a common source of bleeding

3. Mostly incidental finding at autopsy

Clinical manifastation of cerebrovascular diseases

• Strokeor

• Cerebrovascular accident (CVA)


Stroke: variants1. Transient ischemic attacks (TIA)

deficiency resolves within 24 hours

2. Completed strokes

Causes of Stroke or CVA

1. Brain infarction

2. Brain hemorrhage

3. Subarachnoid hemorrhage

4. Miscellaneous

80%

10

7

3


Stroke: Clinical differentiation

Prodromes Onset LOC CSF Blood Headache

Thrombosis TIA Gradual No No No

Embolism Cardiac Sudden No + / - + / -

Sub Hem No Sudden Initially + + + + + +

Intr Hem No Sudden Usual + + + + + Note: Lateralizing sign in all, except Subarachnoid hemorrhage.

LOC=loss of consciousness. Sub=subarachnoid. Intr=intracerebral


Cerebral Edema: Types

1. Vasogenic: fluid in extracellular spacecommon type:infarction, hemorrhage,tumor, trauma

2. Cytotoxic : fluid in intracellular spacehypoxia, ketoacidosis


Summary-1

Ischemia

Pale infarct(slow complete occlusion)

Hemorrhagic infarct(incomplete occlusion)

global (patterns of injury)

Focal vascular occlusion


Summary-2

Hemorrhage

Subarachnoidberry aneurysm (sites, structure)

Intracerebralhypertensive disease(sites, arteriolar changes)

Mixedvascular malformations (types, structure)


CENTRAL NERVOUS SYSTEM TRAUMA


Important Considerations

Location of the lesion

Limited capacity to regenerate

Shape of the object

Force of the impact

Head’s motion


Types of Injury

Open vs. closed

Penetrating vs. blunt

External vs. internal damage

Skull fractures

Parenchymal

Vascular


ConcussionClinical syndrome

Change in momentum of the head

Instantaneous transient neurologic dysfunction,

loss of consciousness, loss of reflexes

Full neurologic recovery

Amnesia

No morphological changes


Contusion

Bruising resulting from transmission of force

through other tissues

Vessel injury, tissue damage, edema

Crests of gyri

Inferior surfaces of frontal lobe, temporal

poles

Anywhere adjacent to fractures (fracture

contusion)

PRINTED BY FILAMEN '05Fronto-temporal contusions


Remote fronto-temporalcontusions


Base of frontal lobes

Contusions


Intact brain tissue

Infarct


Contusions

Lacerations


Coup vs. Contrecoup

Coup lesion: At the site of

trauma, while head is still

Contrecoup: At the opposite

site of trauma, while head is

in motion



Epidural Hematoma

Middle meningeal artery tear

by fracture

May occur without fracture in

children

Clinical presentation several

hours after injury (lucid

interval)


Skull fracture

Fracture

Impression of middle meningealartery

Fro

nta

l

Occ

ipit

al


Bone

DuraEpidural space

Subdural space

Epiduralhematoma



Subdural Hematoma

Bridging vein tear by sudden

movement of brain

Slowly progressive neurologic

deterioration

Evolution:

Lysis of clot (1 week)

Early organization (2 weeks)

Hyalinized connective tissue (1-3

months)


Bridging veinsReflected dura



Subdural clot


Subduralhematoma


Subdural Hematoma

Multiple recurrent

hemorrhages from delicate

granulation tissue vessels

Chronic subdural hematoma

Removal of hematoma and

subdural membrane


Chronicsubdural hematomas


Capillary

Fibroblastic/endothelialproliferation

Fibrin clot

Subdural hematoma, chronic


Internal carotidarteries

AneurysmSubarachnoidhemorrhage


Post traumatic Syndromes

Post traumatic hydrocephalus

Post traumatic dementia,

“punch-drunk” syndrome

(dementia pugilistica)

Post traumatic epilepsy,

meningioma, infection

Post traumatic psychiatric

disorders


Spinal Cord Trauma

Associated with bone injury

Progression of lesion due

to vascular injury

(ischemia) and

excitotoxicity


DISORDERS OF MYELIN


Overview

Primary myelin diseases (multiple sclerosis)

Diseases with secondary damage to myelin (HIV leukoencephalopathy, progressive multifocal leukoencephalopathy-PML,carbon monoxide poisoning)

Dysmyelinating diseases- leukodystrophies


Multiple Sclerosis (MS)

Classical MS, Charcot type

Most common demyelinating disorder

Onset rare in childhood or >50 years of age

Male:Female = 1:2

Relapsing/remitting episodes, gradual deterioration

Clinical findings do not fit into a definitive anatomical distribution


Multiple SclerosisEtiology unknown

Environmental:

Common in N. European & US, rare in orientals

15 years of age

Genetic:

15-20X risk in immediate relatives

HLA-DR2

Chemical

Viral


Multiple Sclerosis

Autoimmune myelin destruction

Experimental allergic encephalomyelitis (EAE)

Increased cytokines, leukocyte adhesion molecules on endothelial cells

CD 4+ and CD 8+ T-cells, and macrophages


Multiple Sclerosis

Most common locations: Optic nerve (unilateral visual impairment), spinal cord (motor/sensory impairment, bladder control problems), brain stem (cranial nerve deficits, ataxia)

Magnetic Resonance Imaging (MRI)

Cerebrospinal fluid

Increased immunoglobulins

Oligoclonal bands


Ventricle

Plaques

Multiple sclerosis


Plaque

Multiple sclerosisMidbrain

Aqueduct

Substantianigra



Acute MS, myelin stain

Cellular lesion,myelin loss

Residual myelin


Acute MS, silver stain


Preserved axons


Chronic plaque, myelin stain

No inflammationMyelin loss,hypocellular

Myelin insurroundingtissues

Sharp border


Chronic plaque, silver stain

Lesion border

Few preserved axons


Other Primary Demyelinating Diseases

Acute Disseminated Encephalomyelitis (ADEM; postinfectious/ perivenous/ postvaccinial encephalomyelitis):

Acute, monophasic, children and adults, with headache, lethargy, coma, rapid progression, 20 % death

Acute Necrotizing Hemorrhagic Encephalomyelitis(ANHE;Weston-Hurst Disease):

After urinary tract infection, M. pneumoniae infection, in children and young adults


ANHE

Numerous petechiaein WM


ANHE, myelin stain

Capillaries

Perivascular myelinloss, inflammation

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Patologi Sistem Saraf.edit