THE NERVOUS SYSTEM

Dr. Grace Widjajahakim, Sp. PA(Anatomical Pathology)

Normal BrainFrontal lobe , parietal lobe, occipital lobe.Midbrain (†)Pons (◊)MO (x)Cerebellum (*)

Globus pallidus (+)Putamen (◊)Caudate nucleus ()Lateral ventricles(□)Hippocampus (x)

I.CEREBRAL EDEMA

• Adalah penumpukan air yang berlebih dalam parenkhim otak.

• Cerebral edema:

Normal Brain

HE Stain

• Hydrocephalus = accumulation of excessive CSF within the ventricular system.

II.CEREBROVASCULAR DISEASE

• 3 proses dasar: 1. thrombotic occlusion of vessels 2. embolic ,, 3. vascular rupture1-2: Loss of oxygen & metabolic

substrates→ischemic injury/ infarct3: Hemorrhage→direct tissue damage

→secondary ischemic injury

Histopatologi

Neural injury dibagi 3: 1.Early changes ( 12-24 jam ): * red neuron

(microvacuolization →cytoplasmic eosinophilia, nuclear pyknosis & karyorrhexis)

* infiltrasi neutrofil sekeliling lesi2. Subacute changes ( 24 jam- 2 mgg ): *nekrosis

jaringan. Khas: >> makrofag, proliferasi pembuluh darah dan reaktif glosis

3. Repair ( > 2mgg ): Khas: seluruh jaringan nekrotik menghilang, struktur CNS hilang dan gliosis

Hemorrhage

Perdarahan Akut: bekuan darah dikelilingi jaringan otak yang edema. Edema hilang, muncul hemosiderofag, ditepi lesi terdapat proliferasi astrosit

(Centre & Right): Necrotic & oedematous

*Vascular malformations: 1. AVM ( Arteriovenous malformations) 2. Cavernous angiomas

3. Capillary telangiectasias

4. Venous angiomas ( varices )

* Hypertensive Cerebrovascular Disease* Vasculitis

Abnormally dilated capillary of widely varying calibre, separated by neural tissue

III.CENTRAL NERVOUS SYSTEM TRAUMA

• Traumatic Parenchymal Injuries• Traumatic Vascular Injury: epidural hematoma,

subdural hematoma, subarachnoid hemorrhage.

IV.Infections of the Nervous System

Ada 4 cara: 1. Hematogenous spread2. Direct implantation3. Local extension4. Peripheral nerves

Epidural & Subdural Infections

• Meningitis:– Acute »Bacterial meningitis

»Viral meningitis– Chronic meningitis » Tubercoluous meningitis

» Neurosyphilis

Acute: Ad 1. Bacterial Meningitis

• Neutrophils fill the entire subarachnoid space

• Abscesses• Phlebitis may also lead to

venous occlusion & hemorrhagic infarction

Acute: Ad 2. Viral Meningitis

• Microscopic examination:• Mild to moderate infiltration of the

leptomeninges with lymphocytes

Chronic: Ad 1. Tuberculous Meningitis• Mononuclear

cells/mixture of PMN & Mono cells

• Arachnoid fibrosis may produce hydrocephalus

• Intraparenchymal mass (brain: tuberculoma)

Chronic: Ad 2. Neurosyphilis

• Perivascular inflammatory plasma cells & lymphocytes

• Cerebral gummas (mass lesions rich in plasma cells).

A chronic meningitis usually involving the base of the brain & sometimes the cerebral convexities & the spinal leptomeninges.

• Necrotic centre of the gumma surrounded by macrophages & plasma cells.

Parenchymal Infections

• Brain Abscesses• Viral Encephalitis• Arboviruses• Herpes Simplex Virus Type 1 • ,, 2• Herpes Zoster• Cytomegalovirus• Poliovirus

• Rabies• HIV• Fungal Encephalitis• Cerebral Toxoplasmosis• Prion Diseases

Ad 1. Brain Abscesses

• Neovascularization around the necrosis

• Edema• Granulation

tissue

Ad 2. Viral Encephalitis

• Perivascular & parenchymal mononuclear cell infiltrates.

• Inclusion bodies

Ad 3. Arboviruses

Characteristically:• Lymphocytic meningoencephalitis (sometimes

with neutrophils) perivascular distribution.• Severe cases: Necrotizing vasculitis + focal

hemorrhages.

Ad 4. Herpes Simplex Virus Type 1

• Perivascular inflammatory.• Cowdry type A intranuclear viral inclusion bodies

in neurons & glia.

Ad 5. Herpes Simplex Virus Type 2

• Manifests in adults as meningitis.• Disseminated severe encephalitis occurs in

many neonates born by vaginal delivery to women with active primary HSV genital infections.

Ad 6. Varicella-Zoster Virus(Herpes Zoster)

Chickenpox, a common childhood infection, is caused by the varicella-zoster virus.

Hemorrhagic lesions of ganglia

Ad 7. Cytomegalovirus

• Localize in the paraventricular subependymal regions of the brain severe hemorrhagic necrotizing ventriculoencephalitis & choroid plexitis.

• A common opportunistic viral pathogen in individuals with AIDS.

Ad 8. Poliovirus

PoliomyelitisA small group of inflammatory cells surrounding the remnants of

an anterior horn cell.

Ad 9. Rabies

Negri body within Purkinje cell cytoplasm ( Negri bodies pyramidal cells of the hippocampus).

Ad 10. HIV Encephalitis

A focal lesion (microglial nodule perivascular multinucleated cells.

Few lymphocytes (CD4 )

Ad 11. Fungal Encephalitis

1. Aspergillosis

Aspergillus infection invasion with thrombosis & subsequent infraction.

•Filamen.•PMN around the vessels (venule & capillary).

2. Cryptococcosis

‘Soap-bubble’ cysts.

Cysts large number of the organism.Fibroplasia & giant-cell formation.

Ad 12. Cerebral Toxoplasmosis

IHC

Toxoplasma gondii infection pseudocyst within an infected cell (cell membrane forming the cyst wall).

Ad 13. Prion Disease

“Mad cow disease” bovine spongiform encephalopathy.

Spongiform change in the cerebral cortex( abundant cortical amyloid plaques, surrounded by spongiform change).

V. DEMYELINATING DISEASES

• Multiple Sclerosis• Guillain-Barrẻ Syndrome

Ad 1. Multiple Sclerosis• Irregular plaques of

demyelination

• Gross cross section of brain showing plaques

Periventricular white matter is a large “plaque” of demyelination.

Luxol fast blue stain for myelin

Ad 2. Guillain-Barrẻ Syndrome

An acute to subacute demyelinating neuropathy that affects both the central and peripheral nervous system and most often develops as an idiosyncratic reaction to vaccination.

Myelin sheaths damaged.

VI. DEGENERATIVE DISEASES

• Alzheimer’s Disease• Parkinson’s Disease• Huntington’s Disease• Diabetic Neuropathy

Ad 1. Alzheimer’s DiseaseAtrophy frontal and parietal regions, also temporal. Characterized: narrowed gyri&widened sulci.

Celebral cortex: neurofibrillary “tangle” (long pink filamen within the neuronal cytoplasm).

Congo red stain: Cerebral artery: amyloid deposition

Silver-stain: Two amyloid plaques appears as a brownish-red dot surrounded by poliferating neurites creating “bull’s-eye” pattern.

Ad 2. Parkinson’s Disease• Loss of dark

pigmentation on substantia nigra.

• Lewy bodies in a neocortex (homogenous pink bodies with a surrounding halo).

Normal midbrain

HE stain IHC

Ad 3. Huntington’s DiseaseGenetic disease caused by an abnormally large number of triplet repeats in the Huntington gene.

Severe loss of small neurons in caudate&putamen with reactive astrocytosis. The head of caudate has become shrunken with ex vacuo dilation of lateral ventricles

Globus pallidus (+)Putamen (◊)Caudate nucleus ()Lateral ventricles(□)Hippocampus (x)

Normal Brain

Ad 4. Diabetic Neuropathy

Diabetic neuropathy is a peripheral neuropathy in which sensory and motor nerves are damaged or destroyed as a result of ischemic microvascular disease and nonenzymatic glycosylation of neuronal component.

VII. TUMORS

A. CENTRAL NERVOUS SYSTEM:# GLIOMAS: - Astrocytoma - Oligodendroglioma - Ependymoma# Poorly Differentiated Neoplasms:

Medulloblastoma# Meningioma# Metastatic Tumors

Central: Ad 1. Gliomas: Astrocytoma

Mitosis

Grade 1-2 ( Moderate pleomorphism)

Grade 3-4

Endothelial cells kapiler proliferasi, lumen sempit

Central: Ad 2. Gliomas: Oligodendroglioma

• Fried egg appearance (round blue nuclei with clear cytoplasm/halo)

Sering dengan:• Calcium deposition in

the media of a small vessel.

Central: Ad 3. Gliomas: Ependymoma

• Cytologically bland, ephitelium like tumor cells forming prominent rosettes

• Characteristic: Perivascular pseudorosettes

Central: Ad 4. Medulloblastoma

Within the cerebellum.

•Small round blue cells rosettes (Homer Wright rosettes).•Malignant neoplasm.•Radiosensitive.

Central: Ad 5. Meningioma

Hyaline bodies Psammoma bodiesWhorled pattern

Central: Ad 6. Metastatic Tumors

From breast

From bronchus

Edema

B. PERIPHERAL NERVOUS SYSTEM:

# Schwannoma

# Neurofibroma

Peripheral: Ad 1. Schwannoma• Left: “Antoni A”

pattern:• Palisading of

tumor cell nuclei, surrounding pink areas (Verocay bodies)

• Right: “Antoni B” pattern:• Looser stroma,

fewer cells, myxoid change

Peripheral: Ad 2. Neurofibroma

• Bundles of wavy, elongated spindle cells

• A lot of intervening pink collagen