THE NERVOUS SYSTEM

Dr. Grace Widjajahakim, Sp. PA

(Anatomical Pathology)
 SISTEM SARAF

SISTEM SARAF PUSAT SISTEM SARAF TEPI

OTAK MED. SPINALIS SERABUT SARAF GANGLION SARAF

 SISTEM SARAF PUSAT

NEURON NEUROGLIA
(SEL SARAF) (JAR. PENYOKONG)

- ASTROCYTES
- DENKRIT - MIKROGLIA
- BADAN SEL/PERIKARYON - SCHWANN CELL
- AKSON - OLIGODENDROCYTES
- EPENDYMAL CELLS
 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
• GRAY MATTER
 Contains neuronal cell
bodies, dendrites and
glial cells
 Six layers composed of
neuron
 Neuron (pyramidal):
 Afferent (sensory)
 Efferent (motor)
• WHITE MATTER
 Contains myelinated
axons →producing
oligodendrocytes
 Hydrocephalus
• Accumulation of excessive CSF within the
ventricular system.
 II.CEREBROVASCULAR DISEASE
• 3 proses dasar:
1. thrombotic occlusion of vessels
2. embolic occlusion of vessels
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 gliosis
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
 Parameter Cairan Serebrospinal pada orang sehat dan infeksi
Protein Glukosa
Sel Bentuk
(g/l) (mmol/l)

Jernih tak
Normal 0-4 limfosit/𝑚𝑚3 0,15 - 0,40 2,7 – 4,0
berwarna

Meninghitis
↑↑ polimorf ↑ ↓ atau tidak ada Opaq dan keruh
Bakterialis

↑ awal polimorf, kemudian Jernih atau

Meningitis Tbc ↓ atau tidak ada
limfosit opalesen

↑ awal polimorf, kemudian Jernih tak

Meningitis Virus ↑ Normal
↑↑ limfosit berwarna

↑ awal polimorf, kemudian Jernih tak

Ensefalitis Virus ↑ Normal
limfosit berwarna
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 • Rabies
• Viral Encephalitis • HIV
• Arboviruses • Fungal Encephalitis
• Herpes Simplex Virus Type 1 • Cerebral
• Herpes Simplex Virus Type 2 Toxoplasmosis
• Herpes Zoster • Prion Diseases
• Cytomegalovirus
• Poliovirus
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.

Marked inflammatory edema

provokes a spongy necrosis in the
cerebral cortex. Mononuclear
infiltration is noted around small
vessels (HE, low power).
 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. Tha patient also had
Alzheimer's disease. A plaque is seen in the left spongiform change).
lower quadrant of the picture.
 V. DEMYELINATING DISEASES
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

 V. DEMYELINATING DISEASES
Ad 2. Guillain-Barrẻ Syndrome (GBS)
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. Another name for the disease is
acute inflammatory demyelinating
polyneuropathy (AIDP). Myelin sheaths
damaged.
This is a low power image of a peripheral nerve in
GBS. It has been stained with a myelin stain (pink).
Note the large areas of myelin loss in the center.
This is a mid-power image of a nerve which has
been stained with a different myelin stain, which
stains the myelin blue. There is patchy myelin loss
within the nerve. You an also see some small round
lymphocyte nuclei.
 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.

Normal Diabetic
 VII. TUMORS
A. CENTRAL NERVOUS SYSTEM:
# GLIOMAS: - Astrocytoma
- Oligodendroglioma
- Ependymoma
# Poorly Differentiated Neoplasms:
Medulloblastoma
# Meningioma
# Metastatic Tumors
Central: Ad 1. Gliomas: Astrocytoma
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
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
 TRAUMATIC NEUROMA
A traumatic neuroma (also known as "amputation neuroma" or
"pseudoneuroma") is a type of neuroma which results from trauma to a
nerve, usually during a surgical procedure. The most common oral
locations are on the tongue and near the mental foramen of the mouth.
They are relatively rare on the head and neck.

Regenerating Axons and Glia (Schwann Cells), but with no direction