Pathology of the Central

Nervous System
Michelle Y. So, M.D.
Lecture I: Vascular
Diseases of the Central
Nervous System
Lecture II: Infections of
the Central Nervous
System
Lecture III: Tumors of the
Central Nervous System
 Lecture I
Vascular Diseases of the
Central Nervous System
Vascular Diseases of the
CNS
 Diseases of the brain parenchyma
secondary to pathologic alterations
of blood vessels supplying and
draining the CNS
 50% of all neurologic disorders
 Mortality Rate:
100/l00,000 population
Brain infarct
- 50
Subarachnoid hemorrhage -
10
Brain hemorrhage
- 30
Part I : Hypoxia, Ischemia
& Infarction
Part II : Intracranial
Hemorrhage
Part III : Hypertensive

Cerebrovascular Disease
 Part I
Hypoxia, Ischemia &
Infarction
 Hypoxia, Ischemia &
Infarction
 Brain – 2% of the body weight
15% of the cardiac
output
20% of the oxygen
consumption
 Hypoxia, Ischemia &
Infarction
 Definitionof terms
1. Hypoxia - reduced oxygen
2. Anoxia – total absence of
oxygen
3. Ischemia – reduction or
cessation of blood flow
4. Infarction – localized
area of ischemic necrosis in an
organ or tissue resulting from
sudden loss of its arterial
 Hypoxia, ischemia &
Infarction
 Causes of CNS Hypoxia /Anoxia
2. Cardiac arrest
3. Vascular obstruction
4. Decreased O2 saturation
5. Decreased hemoglobin
6. Histotoxic agents
 Hypoxia, Ischemia &
Infarction
 Brain parenchymal damage due to
the varous forms of
hypoxia/anoxia is the same
 Hypoglycemia – histologic
effects are similar to
hypoxia/anoxia
 Hypoxia, Ischemia &
Infarction
 Inclinical practice , there
are two general types of acute
ischemic injury:
Generalized – reduced
cerebral perfusion with
widespread bilateral damage
Focal – severe reduction
or cessation of blood flow to a
localized area
Hypoxia, ischemia and
Infarction
Generalized
Hypotension
Cardiac arrest
Focal
Atherosclerosis
Arteriolosclerosis
Embolism
Vasculitis
Morphologic evolution of an
infarct
 Hypoxia, ischemia and
Infarction
 Hypotension
- “Arterial border zone pattern”
- Boundary zone – subject to
reduction in blood flow
- If patient dies immediately
after – no microscopic changes
- After a few days – wedge shaped
hemorrhagic infarction
 Hypoxia, Ischemia &
Infarction
 Cardiac arrest
- “Laminar necrosis”
- Diffuse neuronal necrosis of
the cerebral and cerebellar
cortices
- More severe within the sulci
than the gyri
- Increases in severity from
the frontal and temporal to
the occipital lobes
 Hypoxia, Ischemia &
infarction
- Most vulnerable neurons :
1. 3rd layer of the cerebral
cortex
2. Pyramidal cells of the
hippocampus
3. Purkinje cells of the
cerebellum
- Due to differences in
the intrinsic metabolic
requirements of neurons
 Hypoxia, Ischemia &
infarction
- Cerebral white matter is
relatively spared but
diminished in bulk due to the
loss of neurons in the gray
matter – enlargement of the
ventricles
- Similar pattern of brain
damage
- status
epilepticus
 Hypoxia, Ischemia &
Infarction
Focal
Atherosclerosis
Arteriolosclerosis
Embolism
Vasculitis
Morphologic evolution
of an infarct
 Hypoxia, Ischemia &
Infarction
 Focal lesions
2. Atheroscleosis
- Chief etiologic factor in the
production of cerebral infarction
– cause of thrombosis in 90%
- Most commonly affected
vessels:
Internal carotid and
vertebral arteries
Basilar and middle cerebral
arteries
- Lumen is reduced by up to 90%
before blood flow is impaired
 Hypoxia, Ischemia &
Infarction
2. Arteriolosclerosis (hyaline &
hyperplastic)
- affects mainly the media of
intracerebral arteries with
narrowing of the lumen
- associated with diabetes and
hypertension
 Hypoxia, Ischemia &
Infarction
3. Embolism
Sources of emboli:
- Heart thrombi in post-MI,
valvulitis (RHD),
bacterial endocarditis
- Aorta and neck vessels:
atheroma
- Peripheral vessels : fat
and tumor emboli
 Hypoxia, Ischemia and
Infarction
4. Vasculitis
- Polyarteritis nodosa
- Giant cell arteritis
- Granulomatous angiitis
 Hypoxia, Ischemia and
Infarction
 Morphologic evolution of an
infarct
3 Phases
Coagulation
necrosis
Liquefaction
necrosis
Cavitation
 Part II
Intracranial Hemorrhage
Part II : Intracranial
Hemorrhage

Intracerebral
(hypertensive)
Subarachnoid (berry
aneurysm)
Mixed intracerebral and
subarachnoid
(A-V
malformation)
Intracranial Hemorrhage
 Intracerebral (hypertensive)
Etiology: results from “Charcot-
Buchard” microaneurysms that form
at the bifurcation of small
intraparenchymal arteries.
Associated with age and hypertension
Location : 1. Putamen (55%)
2. Lobar white
matter (15%)
3. Thalamus , pons
and cerebellar cortex (l0%
each)
Intracranial Hemorrhage
Morphology:
1. Small punctate hemorrhages
- fresh round/oval, well-
circumscribed dark red spots
- older lesions – tiny areas
of softening , brown to golden-
yellow in color (hemosiderin)
- predilection for the grey
matter or junction of the
cortex and white matter
Intracranial Hemorrhage
2. “Slit hemorrhages”
- Slit-like pigment stained
areas of softening
- subcortical lesion
3. Gross hemorrhage
- one to several cm. in
diameter
- massive – displacement
/disruption of adjacent brain
tissue, distortion of the ventricles
*End result – leave a cystic
Intracranial hemorrhage
 Subarachnoidhemorrhage
Etiology: results from rupture
of a berry aneurysm (rarely,
an A-V mal)
Morphology: subarachnoid
hemorrhage, hydrocephalus –
sudden blockage of the SAS,
consequent fibrosis
Intracranial Hemorrhage
True aneurysm
- dilatation of the vascular
lumen, yielding all components
of the wall
- focal absence of the media
- aneurysm wall: thickened
intima

adventitia
o
Intracranial Hemorrhage
Location : major arteries at the
base of the brain
90% - internal carotid system
anterior communicating
artery
junction of the carotid
and posterior
communicating
bifurcation of the
middle cerebral artery
l0% - vertebral-basilar system
Intracranial Hemorrhage
Rupture : 90% - 30 to 70 years
old
Events leading to rupture
(?)
- (+) hypertension
- many are
normotensive
Prognosis:
First hemorrhage – fatal in
30%
Intracranial Hemorrhage
 Mixedintraparenchymal and
subarachnoid hemorrhage
Etiology: arteriovenous
malformation – network of
thick-walled vessels of various
diameters, neither purely
arterial nor purely venous
(“arterialized veins”)
 Part III.
Hypertensive
Cerebrovascular Disease
 Hypertensive
Cerebrovascular Disease
Pathologic changes Resultant
CNS lesion
in blood vessels

Atherosclerosis Major infarct

Multiple small infarct

Arteriolosclerosis Lacunae

Binswanger’s Disease
 Hypertensive
Cerebrovascular Disease
 Lacunae

- “Little lakes”
- Collection of multiple small
2-15 mm, small old cavitary
infarcts
- located in the basal ganglia
and thalamus
- usually asymptomatic
 Hypertensive
Cerebrovascular Disease
 Binswanger’s Disease
- Subcortical leukoencephalopathy
- Patchy or diffuse degeneration
of the white matter
- demyelination , irregular loss
of both axons and myelin
- widespread gliosis
- due to decreased perfusion of
the deep white matter
- progressive deterioration of
mental capacity - dementia
 Lecture II
Infections of the Central
Nervous System
 Part I : Meningitis
Part II:
Encephalitis
 Infections of the CNS
 Routesof infection:
1. Bloodstream – most common
2. Direct implantation –
iatrogenic and traumatic
3. Local extension – from
infected air sinuses
4. Peripheral nervous system –
viral infections
 Meningitis
 Signs and symptoms:
Headache
Neck stiffness
Vomiting
Mental confusion
(-) Focal neurologic signs
 Meningitis
 CSF findings
Bacterial
Viral TB
 

PMN’s 

Lymphocytes   

Protein

Glucose  N
Part I. Meningitis
1. Acute pyogenic
(bacterial)
2. Acute lymphocytic
(viral)
3. Subacute/chronic (TB,
fungal)
 Meningitis
 1.Acute pyogenic meningitis
Etiology: Escherichia coli –
neonate
Hemophilus influenza –
infants and children
Neisseria
meningitidis –
adolescents and young
adults
Pneumococcus – very
young and very old
 Meningitis
Microscopic :
PMN’s in the subarachnoid
space , especially
around blood vessels
Complications:
Vasculitis --- infarction
Adhesive arachnoiditis ---
obliterated SAS ---
hydrocephalus
 Meningitis
 2.Acute lymphocytic (viral)
meningitis
2/3 cases – (+) organism
identified – mumps, EB
virus, HS II
Less fulminant clinical
course
Self-limiting
 Meningitis
 3. Subacute or chronic meningitis
A. Mycobacterium tuberculosis
Basal exudate
Tubercle formation with
caseation necrosis,
langhan’s giant cells
Complications:
Vasculitis – infarction
Arachnoiditis –
hydrocephalus
*more commonly seen in
TB than pyogenic
 Meningitis
B. Cryptococcus neoformans
SAS
Mild/marked chronic or
granulomatous
inflammation
Indolent or fulminant
 Part 2.
Encephalitis
1.Bacterial
2. Viral
3. Fungal
 Encephalitis
 1. Bacterial encephalitis
May occur as an extension from
meningitis
“meningoencephalitis”
Primary parenchymal infection ---
focal cerebritis--- abscess
*Focal deficits
*Increased intracranial
pressure
* Ruptures – ventriculitis,
meningitis, sinus thrombosis
 Encephalitis
 A. Tuberculoma
 B. Brain abscess
Produced by:
- direct implantation – traumatic
- local extension – mastoiditis
- hematogenous – from infections in
the heart & lungs (ex. acute
bacterial endocarditis)
* Fibrosis with collagen production –
capsule
* Fibroblasts derived from blood
vessels
 Encephalitis
 C. Neurosyphilis
Meningitic neurosyphilis
Paretic neurosyphilis
- diffuse parenchymal invasion
with
microglial proliferation and gliosis
Tabes dorsalis
- loss of axons and myelin in
the dorsal (sensory)
roots
*Obliterative endarteritis
* Perivascular inflammation – plasma
cells
 Encephalitis
 2.Viral encephalitis
Perivascular and
parenchymal
mononuclear infiltrate
Glial nodules
Neuronophagia – clusters
around foci of necrosis
Inclusion bodies
 Encephalitis
“Tropism”
Herpes zoster – dorsal
root ganglion
Poliomyelitis – anterior
horn
Rabies – neurons
Herpes simplex – inferior
frontal and temporal lobes
Cytomegalovirus - ependyma
 Encephalitis
“Latency”
Reactivated months / years
after initial infection
 Encephalitis
 Subacute Sclerosing
Panencephalitis (SSPE)
-Measles virus; months/years
after infection
-Children
-Progressive deterioration –
personality changes and
involuntary movements
-Gliosis and demyelination;
viral inclusions in the nucleus
of oligodendrocytes
 Encephalitis
 ProgressiveMultifocal
Encephalopathy
-Polyomavirus
-Demyelination with bizarre
giant astrocytes
-Viral inclusions in the
nucleus of oligodendrocytes
 Encephalitis
 Transmissible Spongiform
Encephalopathies (Prion
Diseases)
-”Spongiform changes” in the
grey matter with vacuole
formation
-Prion protein (PrP) – normal
cellular protein in neurons
which undergoes conformational
change from its normal alpha-
helix to an abnormal B pleated
 Encephalitis
A. “Crutzfeld – Jacob Disease “
(CJD)
- Most common
- Cortex
- Mode of transmission – corneal
transplants, electrodes, growth
hormone extracts
- Dementia
- Uniformly fatal – survival of 7
months to a few years
 Encephalitis
 B.Kuru
- Papua, New Guinea
- Cerebellum
- Dementia ; ataxia – terminal
- Mode of transmission -
cannibalism
 Encephalitis
 3.Fungal Encephalitis
- Immunocompromised patients
AIDS
Terminal cases
- Vasculitis esp. with Mucor
and Aspergillus -----thrombosis
-----infarction
- Parenchymal invasion –
Candida and Cryptococcus
 Demyelinating Disease
 MultipleSclerosis
- Between 20 and 40 years old
- Relapsing and remitting ;
progressive
- Paresthesia; motor and
sensory deficits,
incoordination, paraplegia,
ataxia, mental dysfunction
- Irregular areas of
demyelination “plaques”
 Degenerative Diseases
 ParkinsonsDisease
- Stooped posture, slowness of
voluntary movements,
festinating gait,
rigidity,tremors
- Degeneration of dopaminergic
neurons in the substantia nigra
--- decreased dopamine
- Pallor of substantia nigra
 Degenerative Diseases
 Alzheimer’s Disease
– More than 50 years old
– Progressive disorientation,
memory loss and aphasia
– Cortical atrophy
– Microscopic: neurofibrillary
tangles, senile plaques, amyloid
angiopathy, vacuolar degeneration
Lecture 3: Tumors of the
Central Nervous System
 Tumors of the CNS
 Primary – 50%
 Secondary – 50%
 70% of tumors in childhood are
infratentorial (posterior
fossa)
 70% of tumors in adults are
supratentorial
(cerebral hemispheres)
 Tumors of the CNS
 Incidence of intracranial
tumors
PRIMARY NEOPLASMS
50%
Gliomas 80%
Glioblastoma

Astrocytoma
 Tumors of the CNS
 Clinical manifestations
Headache
Disturbance of mentation
Motor weakness
Visual field defects
Cranial nerve palsies
Seizures
 Tumors of the CNS
 Laboratory evaluation
MRI
CT Scan
Tumor biopsy – diagnosis is
important for prognosis and
management
 Tumors of the CNS
 Management

Surgery
Radiotherapy
Chemotherapy
 Tumors of the CNS
 Meningiomas

- Attached to the dura, arising

from meningothelial cells
- Female predominance ;
(+) progesterone receptors
- “Papillary” variant – tends
to recur
- Malignant meningiomas – show
brain invasion, atypia ,
 Tumors of the CNS
 Astrocytomas

Well-differentiated – Grades 1
and 2
Anaplastic – Grade 3
Glioblastoma multiforme – Grade
4
 Tumors of the CNS
 Gradingsystem
A – Anaplasia
M – Mitoses
E – Endothelial cell
proliferation
N - Necrosis
 Tumors of the CNS
 MetastaticTumors
Five most common primary sites
– 80%
1. Lung
2. Breast
3. Skin (melanoma)
4. Kidney
5. GIT
 Tumors of the CNS

Microscopic: well-demarcated
masses of carcinoma cells
 “It is evident at the
conclusion of this broad
overview of diseases of
the central nervous
system, that in number and
in diversity, they rival
the wondrous complexities
of the central nervous
system itself.”
The End