THE NERVOUS SYSTEM

Dr. Grace Widjajahakim, Sp. PA

(Anatomical Pathology)
 Normal Brain
Frontal 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 rupture
1-2: Loss of oxygen & metabolic
substrates→ischemic injury/ infarct
3: 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 lesi
2. 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
Abnormally dilated capillary
of widely varying calibre,
separated by neural tissue

4. Venous angiomas ( varices )

* Hypertensive Cerebrovascular Disease

* Vasculitis
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 spread
2. Direct implantation
3. Local extension
4. 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
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.

• Perivascular inflammatory 
plasma cells & lymphocytes
• Cerebral gummas (mass
lesions rich in 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
• Neovascularizati
on 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

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

Aspergillus infection  invasion with thrombosis &

subsequent infraction.
2. Cryptococcosis

‘Soap-bubble’ cysts.

Cysts  large number of the

organism.
Fibroplasia & giant-cell formation.
Ad 12. Cerebral Toxoplasmosis

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

IHC
 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

Periventricular white matter is a large

“plaque” of demyelination.

• Gross cross section

of brain showing
plaques

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 Disease
Atrophy 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.

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

HE stain IHC
 Ad 3. Huntington’s Disease
Genetic 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

Grade 1-2 ( Moderate pleomorphism)

Endothelial cells kapiler Mitosis

proliferasi, lumen sempit
Grade 3-4
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

Whorled pattern Hyaline bodies Psammoma bodies

Central: Ad 6. Metastatic Tumors

From breast

Edema

From bronchus
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