The Central Nervous

System
Gonzalo B. Roman Jr.,MD.,FPSP
March 4, 2009

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 Central Nervous System
 Principal functional unit is the neuron
 1011 neurons in the human brain
 Mature neurons are permanent cells
 Neurons differ from one another:
– Functional roles (sensory, motor, autonomic)
– Distribution of their connections
– Neurotransmitter they use
– Metabolic requirement
– Levels of electrical activity at a given moment.

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 Characteristics of CNS
 Brain and spinal cord are enclosed within bony
structures.
 Specialized system of autoregulation of cerebral
blood flow
 Absence of lymphatic system
 Metabolic substrate requirement
 Cerebrospinal fluid
 Limited immunologic surveillance
 Distinctive response to injury & wound healing
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 Bony encasement
 Brain and spinal cord
are protected within
bony structures.
 Bone pathology can
damage the CNS.

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 Characteristics of CNS
 Brain and spinal cord are enclosed within bony
structures.
 Specialized system of autoregulation of cerebral
blood flow
 Absence of lymphatic system
 Metabolic substrate requirement
 Cerebrospinal fluid
 Limited immunologic surveillance
 Distinctive response to injury & wound healing
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 Cerebral blood flow
 750 to 900 mL/minute or 15% of resting cardiac
output.
 Controlled largely by autoregulatory or local
mechanisms that respond to the metabolic needs
of the brain.
 3 metabolic factors:
– Increase CO2 – provides stimulus for vasodilatation
– Increase Hydrogen ion – also increase blood flow
– Decreased O2 – increase blood flow

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 Blood-Brain Barrier
 Tight junctions of endothelial cells of brain
capillaries.

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 Blood-Brain Barrier
 Permits passage of essential substances while excluding
unwanted materials.
 Most highly water soluble compounds are excluded from
the brain (e.g. catecholamines).
 Lipid soluble drugs (e.g. chloramphenicol) can enter
more easily.
 Alcohol, nicotine and heroin are very lipid soluble and
rapidly enter the brain.
 Barrier underdevelop during early years of life, so
bilirubin can enter the brain in severely jaundice infants

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 CSF-Brain Barrier
 Ependymal cells covering the choroid plexus are
linked together by tight junctions (Blood-CSF
Barrier)
 Water is transported by osmosis.
 O2 and CO2 move by diffusion.
 Lipids and non-peptide hormones diffuse easily
but large molecules such as protein, peptides,
many antibiotics do not normally get through

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 Characteristics of CNS
 Brain and spinal cord are enclosed within bony
structures.
 Specialized system of autoregulation of cerebral
blood flow
 Absence of lymphatic system
 Metabolic substrate requirement
 Cerebrospinal fluid
 Limited immunologic surveillance
 Distinctive response to injury & wound healing
AUF SOM PATHOLOGY
 Characteristics of CNS
 Brain and spinal cord are enclosed within bony
structures.
 Specialized system of autoregulation of cerebral
blood flow
 Absence of lymphatic system
 Metabolic substrate requirement
 Cerebrospinal fluid
 Limited immunologic surveillance
 Distinctive response to injury & wound healing
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 Metabolic Requirements
 High level of metabolic activity.
 Brain is 2% of body weight
 Receives 15% of resting cardiac output
 Consumes 20% of its oxygen.
 Glucose is the major fuel source.
 Neurons have no glycogen stores and relies
on blood glucose or stores from glial cells.
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 Characteristics of CNS
 Brain and spinal cord are enclosed within bony
structures.
 Specialized system of autoregulation of cerebral
blood flow
 Absence of lymphatic system
 Metabolic substrate requirement
 Cerebrospinal fluid.
 Limited immunologic surveillance
 Distinctive response to injury & wound healing
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 Characteristics of CNS
 Brain and spinal cord are enclosed within bony
structures.
 Specialized system of autoregulation of cerebral
blood flow
 Absence of lymphatic system
 Metabolic substrate requirement
 Cerebrospinal fluid
 Limited immunologic surveillance
 Distinctive response to injury & wound healing
AUF SOM PATHOLOGY
 Characteristics of CNS
 Brain and spinal cord are enclosed within bony
structures.
 Specialized system of autoregulation of cerebral
blood flow
 Absence of lymphatic system
 Metabolic substrate requirement
 Cerebrospinal fluid
 Limited immunologic surveillance
 Distinctive response to injury & wound healing
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 Cells of the CNS
 Neurons.
 Glia.
 Cells of the meninges.
 Cells of the blood vessels.

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 Neuron
 Vary considerably in structure
and size
 Axon lengths vary greatly
 Organized either as aggregates
(nuclei, ganglia) or as
elongated columns or layers
(intermediolateral gray column
of spinal cord)
 Functional domains in
anatomically defined areas (e.g.
occipital lobe – vision)
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 Glia
 Derived from neuroectoderm
– Astrocytes
– Oligodendrocytes
– Ependyma
 Derived from bone marrow
– Microglia.

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 Astrocytes
 Found throughout the CNS in both gray
and white matter.
 Star shape appearance
 Seen in tissue sections with metallic
impregnation techniques

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 Astrocytes - functions
 Believe to act as metabolic buffers or
detoxifiers
 Suppliers of nutrients
 Electrical insulators
 Contribute to blood brain barrier
 Principal cell responsible for repair and
scar formation in the brain.
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Astrocytes – Gold Stain

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 Oligodendrocytes
 Their cytoplasmic processes wrap around
axons of neuron to form myelin
 Damage results to demyelinating disorders
(e.g. multiple sclerosis)

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Oligodendrocytes

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 Ependymal cells
 Line the ventricular system.
 Their disruption is often associated with a
local proliferation of subependymal
astrocytes – ependymal granulations.
 Certain infectious agent (CMV) may
produce extensive ependymal injury.

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Ependymal Cells

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 Microglia
 Macrophage system of the CNS
 Respond to injury by:
– Proliferation
– Developing elongated nuclei
– Forming aggregates about small foci of tissue
necrosis (microglial nodules)
– Congregating around cell bodies of dying
neurons
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Microglia

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 Reactions of Neurons to Injury
 Acute Neuronal Injury
(red neuron)
– Evident 12 to 24 hours
after hypoxia
– Shrinkage of cell body
– Pyknosis of nuclei
– Disappearance of nucleoli
– Loss of Nissl substance
– Intense eosinophilia

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 Reactions of Neurons to Injury
 Subacute and Chronic neuronal injury
(‘degeneration”
– Usually with progressive disease process
– Cell loss
– Reactive gliosis
 Axonal Reaction
– Regeneration of the axon

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 Reactions of Neurons to Injury
 Subcellular alterations
– Neuronal inclusions e.g. aging (lipofuscin)
– Cytoplasmic deposition e.g. metabolic
disorders
– Inclusion bodies of viral infections
• Intranuclear – Herpes (Cowdry)
• Intracytoplasmic – Rabies (Negri)
• Both - CMV

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Herpes encephalitis

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 Reactions of Neurons to Injury
 Some degenerative diseases are associated
with neuronal intracytoplasmic inclusions
– Neurofibrillary tangles of Alzheimer disease
– Abnormal vacuolation of Creutzfeld-Jacob
disease

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Alzheimer’s Disease

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 Reactions of Astrocytes to Injury

 Gliosis
– Most important histopathologic indicator of CNS
injury.
– Glial cells undergo both hypertrophy and hyperplasia.
 Cellular swelling
 Rosenthal fibers – thick, elongated, brightly
eosinophilic structures within astrocytic processes
 Corpora amylacea – represent degenerative
change in the astrocyte
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 Reactions of Astrocytes to Injury

 Glial cytoplasmic inclusions

 Alzheimer type II astrocyte
– Unrelated to Alzheimer disease
– Seen in patients with long standing
hyperammonemia due to chronic liver disease,
Wilson disease etc.

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 Cerebral Edema
 Vasogenic edema
– Integrity of normal blood-brain barrier is
disrupted
– Fluid in intercellular spaces of the brain
– Paucity of lymphatics impairs resorption of
excess fluid
 Cytotoxic edema
– Secondary to neuronal, glial or endothelial cell
injury
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Brain edema

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Brain edema

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 Raised Intracranial Pressure and
Herniation
 CSF pressure above 200 mm H2O in
recumbent position
 Most cases are associated with a mass
effect either diffuse (edema) or focal
(tumors)
 Herniation – displacement of brain tissue
in relation to fixed structures (dural folds,
foramen magnum)
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 Herniation
 Subfalcine (cingulate) herniation
– Unilateral or asymmetric expansion of
cerebral hemisphere
– May compress branches of anterior cerebral
artery

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 Herniation
 Transtentorial (uncinate, mesial temporal)
– Medial aspect of temporal lobe is compressed
against free margin of tentorium cerebelli
– 3rd cranial nerve is compromised – pupillary
dilation
– May also affect posterior cerebral artery,
contralateral cerebral peduncle

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 Herniation
 Tonsillary herniation
– Displacement of cerebellar tonsils through
foramen magnum
– Life threatening due to compression of
respiratory and cardiac centers in medulla
oblongata

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Subfalcine Herniation

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 Hydrocephalus
 CSF produced by choroid plexus within
lateral and fourth ventricle
 Hydrocephalus – excessive CSF within the
ventricular system.
 Most cases are due to impairment of flow
and resorption of CSF
 Elevates the intracranial pressure
 Communicating vs noncommunicating
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Hydrocephalus

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Hydrocephalus

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 CNS Malformations
and Developmental
diseases

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Malformations and Developmental
diseases
 Incidence is 1 to 2%
 Prenatal or perinatal insults may either
cause failure of normal CNS development
or result in tissue destruction.
 Genetic and environmental factors both
play a role
 Toxic compound and infectious agents are
known to be teratogenic
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 Neural tube defects
 Account for most CNS malformation
 Failure of a portion of the neural tube to
close or reopening of a region of the tube
after successful closure

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 Anencephaly
 Malformation of the anterior end of the
neural tube
 Absence of brain and calvarium
 1 to 5 per 1000 live births

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Anencephaly

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 Encephalocele
 Diverticulum of malformed CNS tissue
extending through a defect in the cranium.
 Most often occurs in the occipital region or
in the posterior fossa.

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Encephalocele

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Encephalocele

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 Spina bifida
 Spinal dysraphism
 Bony defect with spinal cord and/or
meninges protruding out.
– Meningocele
– Menigomyelocele
– Meningoencephalocele
– Syringomyelocele

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Spina bifida

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Spina bifida

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 Neural tube defects
 Etiology is unknown
 Diagnosis facilitated by imaging methods
and screening of maternal blood for
elevated alpha fetoprotein
 Recurrence rate in subsequent pregnancy is
4% to 5%
 Folate deficiency during early weeks of
gestation is a risk factor
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 Forebrain anomalies
 Polymicrogyria – loss of normal external
contour of cerebral convolutions, which
appear small, unusually numerous and
irregularly formed.
 Megalencephaly – abnormally large brain
 Microencephaly – small brain
 Lissencephaly (agyria) – smooth surfaced
brain
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Polymicrogyria

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 Forebrain anomalies
 Holoprosencephaly – spectrum of
malformation
– Incomplete separation of cerebral hemisphere
– Mid line facial anomalies – cyclopia
– Arrhinecephaly – absence of olfactory cranial
nerves and related structures
– Associated with Trisomy 13

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Holoprosencephaly

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Holoprosencephaly

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 Forebrain anomalies
 Agenesis of corpus callosum – absence of
white matter bundles that carry cortical
projections from one hemisphere to the
other.

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Agenesis of Corpus callosum

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 Posterior Fossa anomalies
 Arnold-Chiari malformation
– Small posterior fossa
– Misshaped midline cerebellum with downward
extension of vermis through the foramen magnum
– Hydrocephalus and lumbar myelomeningocele
 Dandy-Walker malformation
– Enlarged posterior fossa
– Cerebellar vermis is absent or only rudimentary
– Large midline cyst lined by ependyma
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Syringomyelia and Hydromyelia
 Expansion of central canal of the cord
(hydromyelia)
 Formation of fluid cleft-like cavity in the
inner portion of the cord (syringomyelia)
 Syringobulbia – when brainstem is
involved

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Hydromyelia

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Syringomyelia

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