CNS pathology

CNS
Neurons
• Structural & functional unit of CNS
• Cells constitutes the CNS includes:-
– Oligodendrites - form myelin in a manner
analogous to the Schwann cells of the PNS
(peripheral nervous system)
– Astrocytes - major supporting cells
– Ependymal Cells - line the cerebral ventricles
– Microglia – derived from circulating monocytes,
macrophages
2
 Reactions to Injury
• Different cellular components of the CNS has
different reaction to injury.
Neurons
• Acute neuronal injury (“red neurons”)with in
12- 24 hrs of injury. Leads to cell death
• Sub acute and chronic neuronal injury
(“degeneration”) long standing injury
• Axonal reaction.
 Reaction cotd
• Astrocytes : gliosis it is hypertrophy and
hyperplasia of astrocytes.
• Microglia , the resident macrophages
accumulate form microglial nodules.
 CNS basic continued
• The CNS is protected by the skull (cage), the CSF
(bath) and menengies.
• CSF fluid is secreted by the choroid plexus and
reabsorbed at the arachnoid villi.
• The three layers of menengies are the
• The Dura(pathymeninx)
• The arachnoid and pia (leptomenix)
• NB ;brain doesn’t have lymphatic vessels and
fibroblasts.
 CNS
• The pressure within the cranial cavity may rise
in one of three commonly observed clinical
settings.
1. Generalized cerebral edema
2. Increased CSF fluid ( hydocephalus)
3. Mass lesion
 Cerebral Edema
• is the result of increased fluid leakage from blood
vessels or injury to various cells of the CNS.
• There are two types cerebral edema
1.Vasogenic edema occurs during damage of
BBB(astrocytes)
2.Cytotoxic edema injuy to neurons ,glial cells and
endothelial cells
3.Interstial edema at the ventricles associated with
hydrocephalus
 Hydrocephalus
• is the accumulation of excessive CSF within the
ventricular system .
• Can be caused by impaired flow resorption of
CSF or overproduction of CSF(rare mechanism)
• An increased volume of CSF within the
ventricles expands them and elevate the
intracranial pressure.
 Hydrocephalus continued
• When hydrocephalus develops in infancy before
closure of the cranial sutures, there is
enlargement of the head.
• Hydrocephalus is classified in to two forms
• Communicating( non obstructive)
Hydrocephalus
• Non communicating (obstructive)
Hydrocephalus
• Hydocephalus ex vacua
hydrocephalus externus
communicating

hydrocephalus internus
non-communicating
Hydrocephalus
 Increased intracranial Pressure(ICP)
• The effect of cerebral edema and
hydrocephalus is to increase the cranial
pressure..
• ICP will be complicated by heniation.
• Herniation is the displacement of brain tissue
past rigid dural folds (the falx and tentorium)
or through openings in the skull because of
increased intracranial pressure.
 Herniation continued
• There are sites of herniation
• Subfalcine (cingulate) herniation
• Transtentorial Herniation
• Tonsillar herniation
Herniation
 Malformations and
Developmental Disorders
• Malformations may be associated with single
gene mutations, larger scale genetic
alterations, or exogenous factors.
Neural Tube Defects(common type)
• Failure of a portion of the neural tube to close,
or reopening of a region of the tube after
successful closure, may lead to malformations
involving some combination ofneural tissue,
meninges, and overlying bone or soft tissues.
 Different types of Neural tube defects
• Spina bifida occulta – bony opening only
• Myelomeningocele – meninges and spinal cord
protrusion to the defect
• Meningeocele – Menengies only
• Encephalocele – protrusion of the brain
through the defect
• Ancephaly failure of development of Cerebrum
• Anencephaly
Meningomyelocele
 Head injury
• The physical forces associated with head
injury may result in skull fractures,
parenchymal injury, and vascular injury

• all three can coexist.

 Head injury
• The magnitude and distribution of head injury
is dependent on.
• the shape of the object causing the trauma,
• the force of impact
• whether the head is in motion at the time of
injury
 Skull fracture
• Linear simple Fracture

• Depressed (displaced) skull fracture

• Diastatic Skull fracture If the fracture cross the

suture line
 Parenchymal Injuries
• Concussion

• Contusion

• Laceration
 Concussion
• is a clinical syndrome of altered
consciousness secondary to head injury
typically brought about by
• a change in the momentum of the head (when
a moving head is suddenly arrested by impact
on a rigid surface
 Concussion cotd
• Transient neurologic dysfunction: loss
of consciousness, temporary
respiratory arrest, & loss of reflexes

• Neurologic recovery is complete

 Parenchymal injury
• Contusion is a bruise on the brain
• Laceration penetrating trauma to brain
• Coup – if the contusion occurs at the point of
impact.
• Counter coup if the parenchymal injury occurs
opposite to the point of impact.
Recent brain contusions
Coup

Contrecoup
 Diffuse axonal injury
• affected may be the deep white matter
regions (the corpus callosum, paraventricular,
and hippocampal areas in the supratentorial
compartment)
• Microscopically showing axonal swelling
 Traumatic Vascular Injury
• Vascular injury is a frequent component of
CNS trauma. It results from direct trauma and
disruption of the vessel wall, and leads to
hemorrhage in different anatomic sites.
• There are different forms of vascular injury
based on the vessel injued and the site of
hematoma.
 Vascular Injury cotd
Epidural Hematoma
Occurs following temporal fractures
Injury of Middle Meningeal arteries
Bleeding occurs above the dura associated
peeling of the dura from the skull.
 Epidural hematoma contd
Sudden loss of consciousness during the time
of injury.

Gain of consciousness
• Lucid Interval

Loss of consciousness,vommiting
 consciousness
brainstem nausea
vomiting
 Vascular injury continued
Sub dual hematoma
Hematoma between the dura and arachnoid
layer.
Mostly associated with blunt trauma
Occurs during rupture of the bridging veins
Can be acute manifest with in 48hrs or chronic
manifest months after the first trauma
Chronic subdural hematoma mostly seen in
elderly.
 Vascular injury contd
Complications of head injury
• Posttraumatic hydrocephalus
• Chronic traumatic encephalopathy (CTE,
previously referred to as “dementia
pugilistica”) is a dementing illness that
develops after repeated head trauma.
• Post traumatic epilepsy
• Psychiatric problems
 Cerebrovascular Disease
injury to the brain as a consequence of altered
blood flow—can be grouped into ischemic and
hemorrhagic etiologies
The cerbrovascular disease are collectively
called stroke.
The third leading cause of death in the world.
 Cerebrovascular disease cotd
Stroke can be caused by two mechanisms

• Hypoxia ,ischemia and infarction – embolism

and thrombosis

• Hemorrhage – hypertension and vascular

anomalies
 Cerbrovascular disease cotd
hypoxic Ischemic strokes

Global Focal
Genealized decreased Embolism
Cerbral perfusin Thrombosis
Eg.hypotension Vasculitis
 Cebrovascular disease ctd
Embolism
Cardiac mural thrombi
Atrial fibrilation
Thrombosis
carotid bifurcation
middle cerebral artery
vasculitis
Polyartitis Nodusa
Cerebrovascular disease ctd
Hemorrhagic vascular disease
Lacunar infracts
Slit hemorrhage
Intraparenchymal hemorrhage
Hypertensive encephalopathy
Subarachnoid hemorrhage
Lacunar infarcts in the caudate & putamen
Hypertension hemorrhage
Hypertension hemorrhage
 Cerbrovascular disease ctd
• 50% of intapanechymal hemorrhages are
associated with hypertension and occur in the
putamen(50-60%),thalamus ,pons and cerbral
hemisphers.
• The most frequent cause of clinically
significant subarachnoid hemorrhage is
rupture of a saccular (“berry”) aneurysm in a
cerebral artery
 Infections
• There are four principal routes how the
microbes enter to the brain.
Hematogenous spread
Local extension
Direct implantation
peripheral nervous system
 Meningitis
• Meningitis is an inflammatory process of the
leptomeninges and CSF within the
subarachnoid space, usually caused by an
infection.
• Meningitis could be
• Acute (pyogenic)
• Aseptic(viral)
• Chronic (tuberclosis)
 Acute Pyogenic (Bacterial) Meningitis
• Newborn • Children, adults
– E. Coli – Str. pneumoniae
– Klebsiella- – Neisseria
enterobacter meningitidis
– Listeria – Haemophilus
monocytogenes influenzae
– Streptococci
(Group B)
 Acute meningitis ctd
Risk factors
• Crowding
College
Military
Concomitant respiratory infection
Clinical manifestation of acute meningitis

• High grade fever

• Headache
• Vomiting
• Neck stiffness
• Altered mental status
• Confirmatory diagnosis will be made through
CSF analysis Lumbar Puncture
 Meningitis ctd
• CSF analysis of Acute meningitis
Cloudy ,turbid
Increased opening pressure
Increased number of neutrophils
Protein level will be higher than normal
Glucose level decreased
 CSF
1st Xanthogranulomatous
haemorrhagic tap

2nd Normal CSF (crystal

clear)

3rd turbid CSF

 Acute Aseptic (Viral) Meningitis
• Less fulminant compared to bacterial
meningitis.
• lymphocytic pleocytosis
• the protein elevation is only moderat
• the glucose content is nearly always normal.
• Self limiting
Chronic Bacterial Meningoencephalitis
• Chronic bacterial infection of the meninges
and the brain be caused by
Mycobacterium tuberculosis
Treponema pallidum
Borrelia species
 Tuberculosis
• It may involve the meninges or the brain.
• Tuberculus meningitis manifest with headache
confusion, vomiting and malaise
• CSF analysis
Increased pressure
Leukocytosis (lymphocytes,macrophages)
Protein will markedly increase
Glucose normal or slightly decreased
Tubercloma produce space occupying lesion on the brain.
 Brain tuberculoma
• behave like slowly expanding mass lesions
 Tuberculosis ctd
• The most serious complications of chronic
tuberculous meningitis are

• Arachnoid fibrosis producing hydrocephalus,

• Obliterative endarteritis producing arterial

occlusion and infarction of underlying brain.
 Neurosyphilis
• is a manifestation of the tertiary stage of
syphilis and occurs in only about 10% of
individuals with untreated infection.
• There are three major forms of tertiary
syphilis
• Meningovascular neurosyphilis,
• Paretic neurosyphilis,
• Tabes dorsalis
 Neurosyphilis continued
• Meningovascular neurosyphilis is chronic
meningitis involving the base of the brain and
more variably the cerebral convexities and the
spinal leptomeninges.
• Paretic neurosyphilis is caused by invasion of
the brain by T. pallidum and is clinically
manifested as insidious but progressive
cognitive impairment
 Meningovascular disease
neurosyphilis
• Lymphoplasmactic infiltrates & endaretritis
obliterans
 Neurosyphils continued
• Tabes dorsalis is the result of damage to the
sensory axons in the dorsal roots. (Charcot
joints will be the clinical manifestation.
 Tabes dorsalis

• Pallor and atrophy in the dorsal columns of

spinal cord
Acute viral encephalomyelitis
• Poliovirus attacks neurons of the anterior
horns, brain stem motor nuclei, and motor
cortex => Wallerian degeneration of axons
and neurogenic atrophy of muscles
• Rabies- the virus enters by ascending along
the peripheral nerves from wound sites =>
encephalitis; Negri bodies are
pathognomonic, round to oval eosinophilic
intracytoplasmic inclusions in pyramidal
neurons of hippocampus& Purkinje cells of
cerebellum
• Herpes simplex encephalitis - pantropic
reaction => acute necrotising encephalitis
 Rabies

• Negri body
Herpes encephalitis
Necrotizing inflammation
in herpes encephalitis
HIV associated neuropathologic
changes
1. Opportunistic infections: Toxoplasmosis,
Cryptococcus, etc
2. Primary CNS lymphoma
3. Direct or indirect effects of HIV-1
 Aseptic meningitis
 Encephalitis
 Vacuolar myelopathy
 Cranial & peripheral neuropathies &
myopathies
HIV encepahlitis
 HIV encephalopathy
Multinucleate giant cell
Brain: Toxoplasmosis
 CSF Indian ink preparation
• Cryptococcus neoformans