PATHOLOGY OF THE

CENTRAL NERVOUS SYSTEM

(CNS)
Anatomy
Brain parenchyma is composed of
• neurons
• glia cells
• endothelial cells
• cells of choroid plexus
Neurons: highly specialized postmitotic cells in the cortex, basal
ganglia, anterior horns of the spinal cord; have dendrits and
axons; are very sensitive to ischemia

Bielschowsky-silver
Glia cells:
• Astrocytes (found both in GM and white matter
[WM]): their cytoplasmic processes fix the
neurons; important elements of the blood-brain
barier; responsible for scar formation in the brain

• Oligodendroglia cells (located in the WM): form

myelin sheaths of axon

• Microglia cells: fixed macrophages derived from

bone marrow; become activated in encephalitis
•
• Ependyma cells: line ventricles
Neurons and astrocytes in the gray matter
• Adult neural stem cells are found in the
hippocampus; are capable of generating neurons,
astrocytes, and oligodendroglia cells

• Their role in health and disease is not known

 BASIC REACTIONS OF CNS TO INJURY

• Reactions of neurons

• Reactions of glia cells

• Edema
 REACTIONS OF NEURONS

• Acute injury secondary to global hypoxia or

arterial-occlusion induced ischemia

• The neurons do not tolerate O2 deprivation

• The neurons are selectively vulnerable to O2

deprivation  the injury within minutes!! turns
into irreversible

• Hypoxia affects more prominently the pyramidal

neurons of neocortex and hippocampus, and the
cerebellar Purkinje cells than other neurons
LM
• Red neurons (indicate dead cell): become evident
12 to 24 hours after irreversible hypoxic/ischemic
insult. Features: shrinkage of the cell body, pyknosis
of the nucleus, loss of Nissl substance, intense
eosinophilia of the cytoplasm

• Laminar necrosis: high sensitivity and rapid death of

neurons within layers III and V of the neocortex

• Border zone infarct: wedge-shaped area of

infarction at the border zone between the anterior
and the middle cerebral artery distribution, usually a
few centimeters lateral to the interhemispheric
fissure; may be visible grossly
The patient had myocardial infarction-induced ventricular
fibrillation. He was reanimated, and died 4 days after the
cardial event. Red neurons (*) in the gray matter.

*
*
Chronic injury in
neurodegenerative
disorders

• Neuronal inclusions
(arrow) associated with
aggregated proteins

• Neuronal death: apoptosis;

accompanied by reactive
gliosis (not shown)
REACTIONS OF GLIA CELLS (astrocytes, microglial
cells)

Glial scar

• Phagocytosis of lipids of white matter at site of

injury (e.g., infarction) is carried out by
macrophages derived from the circulation  turn
into foamy ma-s

• Foamy ma-s are replaced by reactive astrocytes

(gliosis), resulting in a glial scar: consists of
cytoplasmic processes of astrocytes, and is devoid
of collagen
Foamy macrophages at site of infarction
 Proliferation of astrocytes  glial scar

Foamy
macrophages

Astrocytes

Astrocytes
Microglia in encephalitis

Microglia cells proliferate, form aggregates around

necrotic foci (microglial nodules), and phagocytose
dying neurons (neuronophagia)
Microglial nodule (encircled) and neuronophagia (arrow)
in encephalitis: microglia cells have cigar-shaped nuclei
CEREBRAL EDEMA

Types

Vasogenic edema - extracellular

• Due to  vascular permeability (blood-brain
barrier dysfunction)  fluid escapes from the
vessels into the IS space localizing between the
neurons and glial cells
• Causes: inflammation, neoplasm
Cytotoxic edema – intracellular

• Due to hypoxic/ischemic injury to neurones and

glia cells
• Fluid accumulation inside the cells (hydropic
swelling)

In many instances, vasogenic and cytotoxic

mechanisms act in parallel
Manifestations of brain edema

• Focal: induced by mass lesion (tumor, hemorrhage,

abscess) or infarction

• Diffuse: induced by global hypoxia

Morphology of diffuse brain edema

• The brain is heavier (>1350 g) and softer than

normal

• Flattened broad gyri, narrowed slitlike sulci

• Compressed lateral ventricles

• On sectioning, fluid sweeps from the cut

surfaces

• + signs of tonsillar herniation

Diffuse brain
edema: ventricular
spaces are
severely
narrowed

Prof. Barzó Pál, Neurosurgery

INCREASED INTRACRANIAL PRESSURE AND
HERNIATION

• The volume of the intracranial contents is fixed

by the skull. Neoplasm, hemorrhage, abscess,
etc. lead to an  in pressure 
• Papilloedema (swelling of the optic nerve head),
nausea and vomiting, headache, and
impairment of consciousness;

• If left untreated, herniation of certain parts of the

brain occurs
Sites of herniation

• Underneath the falx cerebri: subfalcine

• Underneath the free edge of the cerebellar

tentorium: transtentorial

• Into the foramen magnum: tonsillar

 1. Subfalcine herniation
Unilateral mass lesion
forces the ipsilateral
cingulate gyrus to be
compressed Subfalcine
underneath the falx herniation
cerebri
 focal necrosis and
hemorrhage in the
herniated tissue
+
compression of the
anterior cerebral artery
Kumar, Cotran, Robbins: Basic
Pathology 2003
 2. Transtentorial herniation
• Expansion of the
hemisphere  the uncal
gyrus of hippocampus is
herniated underneath the
free edge of the cerebellar
tentorium

Transtentorial
herniation
 2. Transtentorial herniation
•The ipsilateral oculomotor
nerve undergoes
compression: ipsilateral
fixed pupil
• Posterior cerebral artery
compression  occipital
infarction, cortical
blindness
• Cerebral peduncle
compression  upper
motor neuron signs
• Brainstem compression 
cardiorespiratory failure,
Transtentorial
death herniation
 3. Tonsillar herniation
The cerebellar tonsils are
forced into the foramen
magnum and compress
the respiratory and
cardiac centers within the
medulla 
cardiorespiratory failure,
death

Transtentorial
herniation
Tonsillar
herniation
Compression of cerebellar tonsils and medulla
oblongata by the foramen magnum
Striped hemorrhages in the pons in response to tearing
of small vessels(Duret hemorrhages)
HYDROCEPHALUS (HC)

• Cerebrospinal fluid (CSF): produced by the choroid

plexus, circulates through the ventricular system, enters
the cisterna magna through the foramina of Luschka and
Magendie. Subarachnoid CSF is absorbed by the
arachnoid granulations.

• Accumulation of excess quantity of CSF within the

ventricular system

• Primary HC
• Secondary HC
Primary hydrocephalus
• Accumulation of CSF is accompanied by an 
in intracranial pressure, due to
• congenital
• acquired obstruction to CSF flow
Acquired obstruction - sites and causes

• CSF flow through the lateral ventricles and third

ventricle can be obstructed by intracranial or
intraventricular neoplasms

• The cerebral aqueduct, the fourth ventricle, and

the foramina can be obstructed by neoplasm,
organised blood clot or inflammatory exsudate

• The subarachnoid space and arachnoid

granulations can be impaired by organised
inflammatory exsudate or hemorrhage
Consequences

• When HC develops before closure of cranial

sutures, there is enlargement of the head
Hydrocephalus

Preparation of late
Prof Dr. Gellért Albert
SZTE Anatomy Department
Consequences

• When HC develops before closure of cranial

sutures, there is enlargement of the head

• HC developing after fusion of the sutures is

associated with  intracranial pressure,
expansion of the ventricles, and pressure
atrophy of the brain

• HC can be treated via insertion of a ventricular

shunt with a one-way valve system to drain CSF
into the peritoneum
Hydrocephalus: severe enlargement of the ventricles,
atrophy of the brain
 Sec. (compensatory) hydrocephalus

The increase in
CSF volume
occurs following
brain atrophy:
HC ex vacuo

The intracranial
pressure is
normal
 CNS TRAUMA

Frequent, may manifest in:

• Concussion
• Contusion and laceration
• Diffuse axonal injury
• Traumatic intracranial hemorrhage
• Spinal cord injury
Concussion

• A clinical sy brought about closed head injury

characterized by sudden onset and transient
neurologic dysfunction: loss of consciousness,
respiratory arrest, and loss of reflexes

• Associated with WM (axonal) injury

• Recovery is complete, amnesia (loss of

memory) for the events persists
Contusion and laceration

• Contusion (bruising): hemorrhagic necrosis of

superficial cortex, resulting from rapid
deceleration or acceleration of the skull and
brain; it involves a coup lesion at the site of
impact of force and a contre-coup lesion,
diametrically opposite to it

• Associated with laceration (tearing of tissue)

and disruption of vessels  intracerebral
hemorrhage
• Skull fracture is usually present
• Outcome: healing with gliosis; if extensive, may
be lethal
 Fracture contusion with necrosis of GM and WM,
hemorrhage and brain oedema

Contre-coup
Coup
Diffuse axonal injury
(DAI)

Rotational movements
of the brain within
the skull lead to
shearing and tensile
strains on neuronal
processes  DAI in
deep WM regions
(corpus callosum,
paraventricular and
hippocampal areas
and the brainstem)
• Morphology: axonal swelling and focal
hemorrhages

• Clinical features: instantaneous deep coma,

usually fatal

• In survivors, damaged axons undergo

degeneration  loss of fibers in the WM
TRAUMATIC INTRACRANIAL HEMORRHAGE

Hemorrhage is a frequent component of CNS

trauma

Hemorrhage (sometimes in combination) may be

• epidural
• subdural
• subarachnoid
• intraparenchymal

• Without neurosurgical intervention, death in

significant number of patients
The branches of middle meningeal artery run between the dura
mater and the skull
Epidural hematoma
• Temporal bone fracture  rupture of middle
meningeal artery  accumulation of arterial blood
between the dura and the skull: EH
• Lucid interval followed by a rapid  in intracranial
pressure

Prof. Barzó Pál, Neurosurgery

The bridging veins between the dura mater and the arachnoid membrane
Subdural hematoma
Rupture of bridging veins
between the brain and superior
sagittal sinus due to torsion
forces  accumulation of venous
blood between the dura and the
arachnoid: SH

Prof. Barzó Pál, Neurosurgery

Subdural hematoma.
In this patient, the midline structures are shifted to the right

• Acute: rapid increase in

intracranial pressure

• Chronic: change in
personality, memory
loss and confusion,
particularly in
elderly and
alcoholics

Prof. Barzó Pál, Neurosurgery

 Subarachnoidal hemorrhage

• Rupture of arteries of the circle of Willis 

accumulation of arterial blood in the subarachnoid
space

• Meningeal irritation with a rapid increase in

intracranial pressure
Intraparenchymal hemorrhage

• Rupture of small intrinsic vessels in the setting of

brain trauma with contusions and lacerations

 intracran. pressure with focal neurologic deficits;

may be fatal
Outcome of CNS trauma
Minor head injury: satisfactory recovery

Severe head injury: good recovery or patients

remain disabled:
• Post-traumatic epilepsy
• Post-traumatic hydrocephalus: organization of
subarachnoid hemorrhage  disturbed CSF
resorption
• Post-traumatic dementia: due to neuronal loss
and axonal damage; frequent in boxers who
have repeated head trauma during several years
• Persistent vegetative state: in patients with
diffuse axonal injury
 Spinal cord injury

• Fracture/dislocation of the vertebral column 

contusions, nerve fibre transection, hemorrhagic
necrosis in the cord
• Lesions involving the thoracic vertebrae or
below lead to paraplegia
• Cervical lesions result in tetraplegia
• Consequences: incontinence, urinary tract and
pulmonary infections, pressure sores and
muscle wasting