BASIC PATHOLOGICAL

ASPECTS OF NERVOUS
SYSTEM

FKIK UNIB 22
CNS CELLS
Neurones
Glia
Microglialcells
Connective tissue
Blood vessels
  A nerve cell of nervous system that
Neuron sends and receives electrical signals
over long distances within the body.

 Neuron will loss with progressive aging

 Neuron of CNS cannot effectively

regenerate axons over long distance →
limit ability of CNS to respond to
different type of injury

 Infarct
transects internal capsule creates
permanent motor deficit

 Neuron in CNS don’t remyelinate →

therefore demyelinating disease will
cause permanent functional deficit (e.g.
Multiple Sclerosis)
NEURON
REACTION AGAINST INJURY
CHROMATOLYSIS
Cytoplasm swell
Nissl substance
displaced and
marginated
Injury to/transection of
axon
Sometimes: fluid
acumulates (hydrophic
changes)
CHROMATOLYSIS

• Damage to the axon provokes a

series of morphologic and
biochemical changes in the
neuronal cell body; include
disruption and dispersion of Nissl
bodies/ Nissl substance or
chromatolysis

• Disintegration of the Nissl bodies

Anterograde of a neuron as a result of injury or
Normal axon degeneration of
the axon, occur
exhaustion
distal to the site
of injury
NEURON
REACTION AGAINST INJURY
 ATROPHY
◦ On gross examination:
 Reduced weight
 Selective loss in specific
region
◦ Single neuron
 Cell shrivel
 hyperchromatic
 NEURONOPHAGIA
◦ Injury that killed neuron
abruptly caused cell debris,
which will be
phagocytosized
Aggregation of neuron cells
around dead neuron:
NEURONOPHAGIA
GLIAL CELLS

Astrocytes
Oligodendroglial
Ependima
Choroid plexus cell
 ASTROCYTES
 Star-shapedcells
 Neuroectodermal origin
 Function:
◦ Supportive framework for other cells
◦ Control of neuronal environment
◦ Regulation of blood-brain barrier
2 type
◦ Fibrillary astrocytes : white matter
◦ Protoplasmic astrocytes : grey matter
 Reaction against injury
◦ Gliosis
◦ Cells : plump, eosinophilic cytoplasm
(gemistocytes)

Corpora amylacea: product of astrocytes,

located: subpial and subependimal
Gemistocyte astrocyte
OLIGODENDROGLIA
The most numerous cells in CNS
Synthesis and maintaining myelin in CNS
Damage → demyelination
Darkly staining nuclei around neurons and nerve
fibers
EPENDIM
Single cell lining of ventricular system and central
canal of spinal cord
Short columnar cells with cilia
Absorption and secretion of cerebrospinal fluid
During pregnancy, some infection target ependimal
cell and caused aquaductal stenosis → hydrocephalus
PLEXUS CHOROID CELL

Secrete cerebrospinal fluid

Epithelial lining of plexus choroid
CONNECTIVE TISSUE
Meningens
◦ Pia
◦ Arachnoid
◦ Duramater
◦ Arachnoidal granulations : main site of CSF
absoprtion
Perivascular fibroblast
BLOOD VESSELS
• Capillaries differ from other site:
– Vessels are non fenestrated, tight junctions present
– Endothelial cell posses a thick layer of cytoplasm
– Few microvilli
– Endothelial cell basement membrane surrounded
by a network of astrocyte processes

Special structural → important constituent of

blood-brain barrier
 GLIOSIS
• Reaction to injury
• Proliferation of astrocyte
• Evolves in hours to day and persists to an extent that
is usually commensurate with the severity of injury
• Reactive astrocyte :
• gemistocytic astrocyte: exentric plump nuclei,
eosinophilic cytoplasm
• Glial scar: composed of reactive astrocytes and their
processes.
MICROGLIAL
Macrophage/monocyte
Normally quiescent
Hyprechromatic, elongated cell
Reactions:
◦ Proliferate in injury area
◦ 2 pattern
 Microglial nodule
 Microglia and astrocyte create cellular nodule in response to
infection
 Diffuse microgliosis
 Rod cells
 Cell will distended by lipid droplet : gitter cell
 CONGENITAL BRAIN DEFECTS
 Based
on severity of defect on nervous system (NS):
 AGENESIS : There is no formation (anlage) of all or partial

part of NS  IUFD
 APLASIA : There is only NS Streak Formation
 HYPOPLASIA : Failure to growth of all or partial part of NS

 Hypotrophy (Micro Insize) 

Hypofunction / Fatal e.g. Microensephaly,
Arnold – Chiary Syndrome
Defect On Enclosing of the
Neural Tube

There is “Cele”
Formation, or Spina
Bifida Formation
(Occulta /Aperta)
e.g. Meningocele,
Encephalocele,
Myelomeningocele
Spina bifida timbul akibat kegagalan dari
kanalis vertebralis untuk menutup secara
normal karena suatu defek di dalam
perkembangan vertebra
Okulta (tersembunyi)  disebabkan oleh
kegagalan penutupan lamina vertebra yang
terlibat, dapat berupa penonjolan yang
menyerupai kantung dari mendinges dan kulit
penutup dan biasanya tidak mengenai jaringan
saraf yang ada dibawahnya. Hal ini disebabkan
oleh tidak menyatunya lengkung-lengkung
vertebra. Spina bifida okulta ditandai dengan
plak rambut yang tumbuh menutupi daerah yang
cacat.Cacat ini terjadi di daerah lumbosakral
(L4-S1)
Aperta  cacat yang lengkung
vertebranya tidak terbungkus kulit
(terbuka) sehingga rentan terhadap infeksi
sekunder
Kistika  Spina bifida terparah. Tuba neuralis gagal
menutup, lengkung-lengkung vertebra gagal terbentuk,
dan jaringan saraf terpapar. Jaringan sarafnya menonjol
melewati sebuah cacat lengkung vertebra dan kulit
sehingga membentuk kantung mirip kista. Pada spina
bifida kistika bisa terjadi protrusi ruang subarachnoid
yang berisi cerebrospinal melalui defek sehingga
berpeluang terjadi hidrosefalus. Pada beberapa kasus
hanya meninges yang berisi cairan saja yang menonjol
dari daerah cacat (=spina bifida dengan meningokel)
sedangkan pada kasus lain jaringan saraf ikut dalam
kantung tersebut (=spina bifida dengan mieloskisis atau
rakiskisis).
 Spina bifida variations
 These variations can be grouped as:
 Spina bifida aperta : open if the overlying skin is not intact, pending
leakage of cerebrospinal fluid. E.g. : meningocele, meningomyelocele
 Spina bifida occulta : occult if the defect is well covered with full
thickness skin. E.g. : (sacral dimple)

• Meningocele & Myelomeningocele • Spina bifida

Neural placode is exposed. Sacral dimple: dermal sinus

track with spina bifida
 HYDROCHEPALUS

TYPE :

1. COMMUNICANS : obstruction occurs

outside ventricle system

2. NON-COMMUNICANS

3. EXVACUO (COMPENSATED)
HYDROCEPHALUS
Non-communicating hydrocephalus
◦ There is obstruction to CSF
 Congenital malformation
 Neoplasm
 Inflammation
 Haemorrhage
Communicating hydrocephalus
◦ There is no obstruction but the reabsorption is
impaired
HYDROCEPHALUS
Primary hydrocephalus
◦ Accompanied by increased intracranial pressure
◦ Due to:
 Obstruction
 Congenital
 Acquired
 Impaired CSF absorption
 Excess CSF production

Secondary hydrocephalus
◦ Compensatory to loss of cerebral tissue
 Sites of Obstruction
 Inflammatory exudate and
organizing hemorrhage
1. Subarachnoid space
2. Arachnoid granulation
 Intracerebral and
intraventricular neoplasms
3. Choroid plexus
4. Lateral ventricles
5. 3rd ventricle
 Neoplasms, hemorrhage,
inflammatory exudate
6. Cerebral aquaduct
7. 4th ventricle
8. exit foramen
 OBSTRUCTIVE
HYDROCEPHALUS

( NEOPLASM )
 OBSTRUCTIVE
HYDROCEPHALUS

( INFECTION )
TRAUMATIC
DISORDERS
 TRAUMA
Penetrating wounds produce hemorrhage and blast effects.
Velocity contributes a blast effect to a projectile
High-velocity : it disrupts tissues by its own mass and also
centrifugal blast that enlarges the diameter → immediate death
Low-velocity : Seizures are threat in healed penetrating
wounds, 6-12 mo after : collagenous tissue is displaced in the
brain

HIGH VELOCITY BULLET LOW VELOCITY BULLET

WOUND WOUND
HEMORRHAGIC TRACT
(PENETRATING WOUND)
Traumatic intracranial haemorrhage
 Subdural hematoma
 Significant cause of death from falls, assaults, vehicle accidents,
sports injury
 Frontal/occipital area is struck by blunt object → cerebral
hemisphere displaced in an anteroposterior direction → hit
against inner aspect
 Soft cerebral tissue becomes compact then recoil → shearing
effect
 Usually stop after 25-30 mL venous bleeding
SUBDURAL HEMATOMA
Accumulation of blood in subdural space
Bleeding from torned bridging vein
Significant cause of death after head
injuries from falls, assault, vehicular
accident, sport mishap.
Child abuse
Subdural Hematoma
If frontal or occipital lobe strikes a fixed object or
stationary head struck by blunt object, cerebral are
displaced in anteroposterior direction
The movement of brain and skull are in opponent
direction
It will make a shearing effect between dura and
subarachnoid, and will be filled by blood
The bleeding will stop when it reaches 25-50 ml
Compression of severed vein will initiate
thrombosis
 SUBDURAL HEMATOMA : pathology

Expansion of the hematoma will often result

in re-bleeding
Creates new hematoma adjacent top the outer
membrane
Will develop into second inner membrane
 Subdural hematoma

Headaches (meningens stretching)

Contralateral weakness
Seizures (focal irritation)
Impair cognitive function
Dementia
Rebleeding : initiate transtentotial herniation
 Subdural hematoma resolution
 Tissue response
 Formation of granulation tissue → outer membrane
 Fibroblast from outer membrane moved into the hematoma →
inner membrane : 2 weeks
 Evolution:
◦ Reabsorb leave a small amount of hemosiderophage
◦ Remain static, with potential for calcification
EPIDURAL HEMATOMA
 Middle meningeal artery branches splay across temporal-
parietal area
 Hemorrhage into epidural space, separating dura from
calvaria
 4-8 hours: asymptomatic
 30-50 mL: intracranial pressure increased → exceed venous
pressure → circulatory stagnation and cerebral ischemia →
global cerebral hypoxia
Epidural Hematoma
Accumulation of blood between calvarium and
duramater
Result of the blow to the side of a temporal bone
fracture
A. meningeal media occupies the space between
duramater and calvarium and grooved into the
temporparietal area.
Trauma to temporal bone leads to a fracture,
because it is the thinnest bone so it will
transectioned the A. meningeal media, and lead
to life-threatening epidural hemorrhage
 Pathophysiology Epidural Hematoma
• Transection of the A. meningeal media permits
arterial blood escape into epidural space
• Slowly, after 4-8 hours asymptomatic
• Symptoms after hematoma attained 30-50 ml
• When intracranial pressure exceed venous
pressure, venous sinuses compressed,
circulatory stagnation caused cerebral
ischemia and hypoxia. The patient manifest
cortical impairment such as confusion and
disorientation
 EPIDURAL HEMATOMA
• Cushing reflex : protective response
• Heart Rate slow to increase ventricular filling
• Systolic pressure increased

• Compensatory mechanism :
temporal lobe displaced downward → transtentorial herniation →
life threatening

• Herniation compress uncus/hyppocampus against midbrain and other

structures → 3rd cranial nerve damage (oculomotor nerve)

• Paralysis of the oculomotor nerve results in :

• drooping eyelid (ptosis),
• deviation of the eyeball outward (and therefore double
vision) and
• a dilated (wide-open) pupil.
SUBARACHNOID HEMORRHAGE

Bleeding into subarachnoid space

Most cases relects the rupture of preexisting
arterial aneurysm
Trauma
Blood dyscrasia, infection, vasculitis, tumors
 CEREBRAL CONTUSION
 Result of energetic anteroposterior displacement when moving
head strikes a fixed object
 Floatation of cerebral hemisphere in AP direction and
gelatinous quality of cerebral tissues creates vulnerable to
bruising /laceration particularly the mid-sagittal plane
 Magnitudes of contusion parallel the velocity of the motion
and abruptness of the decelleration
 Cerebral contusion occur at the point of impact: coup
contusion
 When the occipital area are strikes, abrasions are prone to
occur in the brain opposite of the point of impact : countre-
coup contusion
CEREBRAL CONTUSION: pathology
Minimal force : contusion limited to gray
cortex and restricted to the gyry’s apex
Greater forces : extend into the white
matter or lacerate the cortex and initiate
cortical/subcortical hemorrhage. Edema
and hemorrhage create a mass lesion →
trantentorial herniation
CEREBRAL CONTUSION: pathology
Bruised, necrotic tissue will be phagocytized
Astrocytic proliferation forms a local scar
Contusion to cerebrum may be internal and
apparent on microscopic only
Axon will be broken, retract into spheroid,
myelin lost
Occur in parasagital white matter, accompanied
by hemorrhage → comatous
CT-scan : edema without hemorrhage
MRI : small hemorrhage and edema
CEREBRAL CONTUSION
• Diffuse axonal injury : result of shearing and
tensile strain on neuronal processes because
of rotational movement of brain within skull
• 2 main component:
– Small hemorrhagic lesion in corpus callosum and
dorsolateral portion of brainstem, healed by
gliosis
– Diffuse damage to axons : microscopically
detected : damage axon undergo anterogade
degeneration, resulting in a loss of fibres in white
matter
CEREBRAL CONTUSION: secondary
brain damage
Intracranial hemorrhage
Traumatic damage to extracerebral
arteries
Intracranial herniation
Hypoxic brain damage
Meningitis
 CEREBRAL CONTUSION : outcome of
non-missile head injury
Patient with minor head injury will have a
satisfactory recoveries
20% of severe head injury make a good
recovery
10% remain disabled
Important cause of persisting debility are:
◦ Post-traumatic epilepsy
◦ Post-traumatic dementia : neuronal loss and axonal
damage
◦ Persistent vegetative state
HERNIATION SITES OF
HERNIATION
1. Cingulate gyrus
under falx cerebri
2. Hippocampal
uncus and
parahippocampal
gyrus over
tentorium cerebeli
3. Cerebelar tonsilar
through foramen
magnum
4. Any defect in the
dura and skull
NEURODEGENERATIF
DISORDERS
Focus on neurodegenerative disorders
Cognitive disturbance (dementia)
 Degeneration involving cerebral cortex, e.g. Alzheimer
disease
 Parkinson’s disease (Lewy body dementia)
Prion Disease
 Spongiform encephalopathy e.g. Kuru, Creutzfeldt Jakob disease
(CJD)
Spinal cord degenerative, e.g. Amyotrophic
Lateral Sclerosis
Toxins effect to CNS
DEGENERATIVE DISORDERS
CT scan Head
generalized cerebral atrophy
 ALZHEIMER DISEASE
 Most common cause of dementia accounting for more than half
of the cases (second most common cause: vascular disease)
 Dementia: Impairment of previously attained occupational or
social functioning due to persistent impairment of memory
associated with an impaired intellectual function in one or more
of the following domains: language, visuospatial skills, emotion,
personality, cognition in the presence of normal consciousness.
 Alzheimer disease: Progressive course over 5-10 years; patients
become immobile and mute
 Risk factors: aging, head trauma, menopause, low educational
level
 Protective factors: anti-inflammatory and antioxidant drugs,
estrogen, high educational level
ALZHEIMER DISEASE
 Geneticdefects in familial cases have
been identified on 4 chromosomes
(Blennow et al, 2006):

Chromosome Gene

21 (Down syndrome) Amyloid Precursor Protein (APP)

19 Apolipoprotein E (ApoE)

14 Presenilin 1 (PSEN1)

1 Presenilin 2 (PSEN2)
Alzheimer Disease
• Insidious and progressive
neurologic disorder
characterized,
 Clinically by:
◦ loss of memory (eventual
dementia),
◦ cognitive impairment
 Pathologically by :
• Aβ-containing senile
plaques and
neurofibrillary tangles
formed by tau filaments
 Parkinsonism (Lewy body dementia)
 Parkinsonism, the most common syndrome with Lewy bodies, is a disease
developing in middle age. In older persons, a mixture of cognitive,
autonomic, and motor dysfunction is more common.

 In Parkinson disease, the Lewy bodies are found in the substantia

nigra of the midbrain, coupled with the loss of pigmented neurons.

 Diseases with Lewy bodies should also be considered in the differential

diagnosis of a wide range of clinical presentations including episodic
disturbances of consciousness, syncope, sleep disorders, and unexplained
delirium. (Brown, 1999)
 PRION DISEASE
(spongiform encephalopathies)

• Spongiform encephalopathy:
Kuru and CJD, fatal familial insomnia.
• Transmissible neurodegenerative disease
• Infectious agents is prion protein

KURU CREUTZFELD-JAKOB DISEASE (CJD)

• Already extinct
• The Fore people that live in
Papua New Guinea.
• Known as Laughing sickness,
trembling
• Canibalism, spread the disease
• Symptoms begin insidiously
• 6 months exhibits severe
dementia
• Death in 1 year
The agent associated with CJD appears to be a prion protein (PrP), a
neuronal cell surface sialoglycoprotein that is encoded by just 3
exons of the PRNP gene on chromosome 20.

It is thought that the normal cellular prion protein, designated PrPc, is
converted via a conformational change to an abnormal form of PrP,
designated PrPSc, that is protease-resistant and can accumulate in
the central nervous system of affected persons.

This accumulation of abnormal protein, thus designated PrPres.

The accumulation of PrPres leads to loss of neuronal cell function,

vacuolization, and death. (Prusiner, 1998) (Markus et al, 2005)
CREUTZFELD-JAKOB DISEASE (CJD)

Spongiform vacuolation (arrows) accompanied by neuronal loss and active

astrocytosis.
Prion disease
Sporadic
Inherited
Iatrogenic
New variant CJD
Sporadic
75%
1:1.000.000
Polymorphisme codon 129
Classical features
◦ Dementia
◦ Myoclonus
◦ EEG : Periodic spike-wave complexes
Inherited / Genetic
15%
Gertsmann-Straussler-Scheiner
syndrome(GSS)
◦ Spinocerebelar ataxia with dementia
Fatal familial insomnia
◦ Profound disturbance of sleep-wake cycles
◦ Signs of pyramidal and cerebellar
dysfunctions
◦ Mutation codon 178 PRNP gene
Iatrogenic CJD
Hormone injection
◦ Human growth hormone (55 cases)
◦ Human pituitary gondotropin (5 cases)
Tissue grafts
◦ Duramater (11 cases)
◦ Cornea (1 case)
◦ Pericardium (1 case)
Medical devices
◦ Depth electrode (2 cases)
◦ Surgical instruments (not definitely proven)
 New variant CJD
 Identified following surveillance following Mad Cow Disease / BSE
(Bovine Spongiform Encephalopathy) epidemic in UK. These cases are
known as variant Creutzfeldt-Jakob disease (vCJD).

 An outbreak of BSE among cattle in England in the 1980's was followed by

the appearance of rare cases of a CJD-like illness in the 1990's that were
characterized by :
◦ Younger age of onset (mean age 26; compared to 65 in sporadic),
◦ lack of characteristic EEG findings (Dysesthesia),
◦ longer course of disease, and
◦ more extensive spongiform change with PrP plaques in the cerebrum and cerebellum of
affected persons, than in sporadic CJD.
◦ Spongiform in basal ganglia and thalamus

 Cases of vCJD continue to appear in regions were BSE was prevalent.

(Johnson, 2005)
AMYOTROPHIC LATERAL SCLEROSIS

• Males are affected more commonly than females.

• The patients present in middle age with weakness of the
extremities and may go on to develop bulbar signs and
symptoms.
• Sphincter control, sensation, intellectual function are not
affected by ALS.
• The course is usually 2 to 6 years after diagnosis, but
patients presenting with bulbar signs and symptoms have
a shorter life span because of swallowing difficulties and
aspiration.
• The etiology is unknown. (Lowe, 1994) (Walling, 1999)
ALS

 Left. Normal spinal cord. Many ascending (blue) and descending (green) traverse the
spinal cord.
 Right. ALS, degenerative disorder. Disruption the pathway (red)
 Amyotrophic Lateral Sclerosis
 ALS results from loss of motor
neurons. This is most striking in the
anterior horn cells of spinal cord with
loss of lower motor neurons, marked
initially by muscle fasciculations.
 The loss motor innervation
eventually leads to muscle atrophy.
 Astrocytosis is seen in response to
the loss of motor neurons.
 With loss of upper motor neurons
there is lateral column degeneration
with gliosis, the so-called "sclerosis"
A. Amyotrophic Lateral Sclerosis (ALS)
of the lateral columns of spinal cord. B. Normal
Toxin effect to CNS
Terima
kasih