Download Intracerebral hemorrhage

Pathology of
Nervous System (I) -2
2016
Dr. Mohammed Alorjani, EBP
Cerebrovascular
Disease
General concepts about vascular
anatomy related to pathophysiology
of cerebrovascular disease (stroke)
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Superficial vessels are most commonly
occluded by emboli.
Deep penetrating vessels are most
commonly affected by hypertension.
Watershed zones are the border zones
at junction between two main arterial
territories. Vulnerable to hypotension.
Anastomoses

The integrity of these anastomoses influences the
brain’s ability to withstand the effects of focal
vascular occlusions
1. Circle of Willis
– Connects anterior and posterior
circulations
– Connects right and left sides
2. Extracranial & intracranial anastomoses
3. Thyrocervical, deep cervical, or occipital
arteries to vertebral artery
4. Leptomeningeal vessels to superficial cortical
vessels
Pathophysiological Facts:
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For maintained normal brain function:
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Continuous blood flow - 15% of cardiac output
High oxygen requirement - 20% of O2
Maintenance of glucose
Hypoxia  irreversible damage in 5-7minutes
↓ BP ≤ 50 mm.Hg is critical 
Hypoxia & ischemia
BP ≥ 200 mmHg critical! 
risk of Hemorrhage
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STROKE
Cerebrovascular Accident
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STROKE:
Acute neurological dysfunction occurring as
a result of a vascular process, causing death
or lasting damage.
TRANSIENT ISCHEMIC ATTACK (TIA):
Transient episode of neurologic dysfunction
caused by focal brain ischemia, lasting few
minutes to 24 hrs. without acute infarction &
without loss of consciousness.
Differential diagnoses of strokes or TIA
include:
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Brain tumors
Cranial or peripheral nerve palsy
Hypoglycemia
Multiple sclerosis
Migraine
Epileptic seizure
Imaging studies (CT & MRI) are IMPORTANT in
the differential diagnosis
Types of Cerebrovascular Disease:

A- Impairment of blood supply &
oxygenation of CNS tissue:
– Global Hypoxic/Ischemic encephalopathy
due to generalized  cerebral blood flow
– Infarction: localized vascular obstruction

Hypoxia may be:
– Functional:
i- Causes leading to ↓(pO2)
ii- Impaired O2 carrying system
iii- Inhibition of O2 use by the tissue
– Ischemic hypoxia:
i- Transient
ii- Permanent
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B- Rupture of CNS blood vessel:
– Intracerebral hemorrhage
– Subarachnoid hemorrhage
– Subdural hemorrhage
– Epidural hemorrhage
1- GLOBAL HYPOXIA
Definition:
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Failure of auto-regulatory mechanisms in
the brain when B.P drops < 50mmHg
leading to poor perfusion & hypoxia.
Symptoms vary from mild confusion to
lasting damage
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Causes include:
– Cardiac arrest
– Ineffective cardiopulmonary resuscitation
– Prolonged anesthesia
– Prolonged hypoglycemia
– Trauma
Features of global hypoxia:
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Selective Vulnerability of neurons in certain
locations:
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Pyramidal cells in hippocampus
Purkinje cells of the cerebellum
Neurons in basal ganglia
Cortical neurons especially in arterial
boundary zones supplied by end
arteries (Watershed Areas)
Watershed Areas of selective
vulnerability:
– Cells: neurons > glia but
all if severe & prolonged
– Regions:
 CA1 region of
hippocampus
(Sommer’s sector),
see red arrow
 Purkinje cells of
cerebellum
 Large cortical neurons
in layers 3 and 5
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Watershed (Borderzone) infarcts include:
– Boundary between anterior & middle
cerebral arteries (Cerebral Convexities)
– Boundary between superior & posterior
cerebellar arteries (Posterior cerebellum)
– Necrosis few centimeters lateral to
interhemispheric fissure
Watershed Vascular Territories
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MORPHOLOGY:
Macroscopic changes: after 24-48 hrs.
Symmetrical & Bilateral
– Brain swelling with blurred demarcation
between grey & white matter, ± small
hemorrhages
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Microscopic changes:
* Acute: after 12 hrs. acute neuronal
necrosis in layers 4 – 6 of cortex
RED NEURONS
few neutrophils followed by glial cell death
* Subacute changes: 24 hrs – 2 weeks
tissue necrosis, macrophages & gliosis
* Repair after 2 weeks: irregular neuronal
loss, gliosis & brain atrophy.
Morphology of lesions:
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Laminar necrosis in areas of hippocampus &
Purkinje cells in more sensitive layers of cells
(Linear portion of the mid-zone of the cortex is
involved)
Boundary zone (Watershed) infarcts:
Bilateral symmetrical wedge shaped discolored
areas just lateral to inter-hemispheric fissure
Sickle shaped band of necrosis on cortex
Watershed Infarcts
Pseudolaminar Necrosis
RED NEURONS
Outcome:
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Depends on
– Age
– Duration of ischemia
– Magnitude and rapidity of reduction of flow
Result varies from persistent neurological deficit
to brain death  Deep coma & flat EEG
Patients maintained by mechanical means
Brain autolysis & respirator brain
2- INFARCTION (Focal Ischemia)
Definition:
Focal brain necrosis due to complete
and prolonged ischemia that affects all
tissue elements; neurons, glia, and
vessels.
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Infarcts account for 80% of CVA
Patients with TIA - Infarction in 5 years
Family history of stroke
? Genetic marker
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Risk factors are:
– Atherosclerosis
– Diabetes, Hypertension, hyperlipidemia
– age
– Cardiac arrhythmias & Cardiomyopathy
– Hypercoagulable states
– Smoking
– Use of contraceptive pills
– Cerebral amyloid angiopathy
– Vasculitis: inflammatory or autoimmune
Mechanisms leading to infarction:
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Thrombotic occlusion: Ischemic/ pale
Carotid bifurcation
Origin of middle cerebral artery
Basilar artery at either end
Embolic occlusion: hemorrhagic/ red
Source: heart or atherosclerosis in carotid
Middle Cerebral a. most affected
Least likely affected is basilar artery
Embolism is more common than thrombosis
& may lead to multiple small infarcts
Other emboli are fat, bone marrow, air,
amniotic fluid
Types of regional infarction
Acute white infarct in the distribution of the Acute red infarct in the distribution of the
right middle cerebral
right anterior cerebral.
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Infarcts due to large vessel occlusion are
REGIONAL
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Outcome depends on:
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Site of occlusion
State of collateral circulation
Systemic perfusion pressure
Degree of atherosclerosis
Rapidity of onset
Macroscopic appearance:
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No gross change before 48 hrs
Soft swollen pale or hemorrhagic WEDGE
SHAPED infarct involving grey & white matter.
Blurred demarcation, & surrounding hemorrhage
due to reperfusion of infarct
After 10 days-3 weeks: liquefaction
Cavity within 1- 6 months
Severe edema with herniations may modify the
picture
Regional Infarction
Microscopic appearance:
– After 12 hrs.
– Very similar to global ischemia but more
regional, with viable thin subpial layer
– Neutrophilic response is present followed
by macrophages ( GITTER CELLS)
A) EDEMA
B) “RED” NEURONS
C) POLYs
D) MACROPHAGES
E) GLIOSIS
Histopathologic
progression of
CNS infarcts
Gitter Cells
Old infarction
REMEMBER THE GENERAL RULES FOR
DATING INFARCTS:
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RED Neurons 12-24 hours
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Neutrophils 24-96 hours
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Macrophages peak at 7-14 days
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Astrocytosis begins after a period of days
& peaks after several weeks
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Macrophages leave after several weeks,
reactive astrocytes remain, initially in
great numbers.
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Therefore:
– Lots of astrocytes & few
macrophages means a lesion that is
many weeks or months old
– A lesion with sheets of macrophages
& relatively few reactive astrocytes
is 1-2 weeks old
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Clinical picture: linked to site of
infarction
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Contralateral hemiparesis
Spasticity
Loss of sensation
Visual field abnormalities
Aphasia …… etc.
Chronic complication of old infarct:
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Cerebral infarctions with a residual cystic
space results in Wallerian degeneration of
descending corticospinal tracts
Wallerian degeneration is axonal
degeneration distal to infarct with myelin
disintegration
Loss of myelin in Corticospinal Tracts
VENOUS INFARCTION
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Venous infarction usually
results from venous sinus
thrombosis
Risk factors: oral
contraceptives, inherited
thrombophilias, cancer, &
in infants; dehydration
Very hemorrhagic
• Lesions are bilateral
due to occlusion of
the superior sagittal
sinus, and affect the
cortex adjacent to the
falx
(parasagittal cortex).
3- INTRACRANIAL
HEMORRHAGE
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According to location, divided into:
• Intracerebral
• Subarachnoid
• Epidural & Subdural
 According to pathogenesis:
• Primary hemorrhage
• Secondary to infarcts, tumors or trauma
 Most common cause of primary intracerebral
hemorrhage is HYPERTENSION
I- Primary Intracerebral Hemorrhage:
Causes:
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Hypertension (50%)
15% of death in hypertensive patients
Other causes:
Cerebral Amyloid Angiopathy
Vasculitis
Bleeding disorders
Tumors
1-Hypertensive Cerebrovascular Disease:
Vascular lesions in hypertension include:
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Atherosclerosis in large vessels
Hyaline arteriolosclerosis of deep penetrating
arteries in basal ganglia, thalamus, cerebral
white matter, pons & cerebellum → hemorrhage
Arteriolosclerosis in vessels ≤ 150 µ → lacunar
infarcts
These result in the following:
C.N.S. lesions in hypertension
• Lobar Parenchymal hemorrhage
• Slit Hemorrhages:
Rupture of smaller penetrating vessels
heal as slit spaces
• Charcot Bouchard Microaneurysms
Microaneurysms in vessels ≤ 300 µ in
basal ganglia
• Lacunar Infarcts:
Tiny cystic infarcts in deep grey matter of
basal ganglia & pons due to hypertensive
arteriolosclerosis. Most are asymptomatic.
HYPERTENSIVE HEMORRHAGE
“SLIT” HEMORRHAGE(s)
Lacunar infarcts in the caudate and
putamen.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 March 2008 08:33 AM)
© 2007 Elsevier
Hypertensive Encephalopathy:
Diffuse cerebral dysfunction, with edema &
↑ ICP
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Acute:
– Headaches
– Confusion
– Anxiety
– Convulsions
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Chronic:
– Dementia (MID, Multi-Infarct-Dementia)
– Gait Disturbances
– Basal Ganglia symptoms
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2- Cerebral Amyloid Angiopathy:
Amyloid is deposited in wall of medium &
small meningeal & cortical vessels result
in superficial lobar hemorrhage.
3- Vasculitis Associated Hemorrhage:
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Inflammatory e.g. Syphilis, TB, Aspergillosis,
CMV
Primary angiitis of the CNS
Polyarteritis nodosa
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Morphology of hemorrhage:
- Well demarcated hematoma & edema
- Usually with massive displacements &
herniations → Duret hemorrhage
- Little necrosis, no inflammatory response
- May extend into ventricle or subarachnoid
- Later cavity with brown fluid; hemosiderin
laden macrophages & gliosis
Intracerebral hemorrhage into lateral ventricle
II-Subarachnoid Hemorrhage:
Causes:- Vessel Rupture
1- Ruptured saccular (berry) aneurysm
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Other aneurysms: atherosclerotic,
mycotic, dissecting, traumatic  occlusion
2- Arteriovenous malformation
3- Hemangioma, telengiectasia….etc
A- Saccular (Berry) aneurysm:
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Commonest cause of spontaneous subarachnoid
hemorrhage F  M , age  50 y
Cause ? Congenital ? acquired weakness of the
media  projection not present at birth. occur at
places where the media and elastica of the vessel
display a congenital defect  weak wall
? Vascular marker (9p21)
In 1/3 of cases rupture initiated by acute increase in
intracranial pressure
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Up to 90% in anterior & middle part of
Circle of Willis, arise in arterial
bifurcations, 20-30% multiple
Incidental in 1%
Rupture in 4 - 5th.decade, at apex,
induced by straining, labour…etc
Sites of Berry
Aneurysm
Apex/ Site of rupture
Neck/ Base of aneurysim
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Size usually  3mm. But may be much
larger
Few large lesions ( up to 25 mm.) may not
rupture, may contain thrombus &
calcification  local P. effects
Composed of wall of thickened intima,
hemosiderin in adjacent brain
Berry aneurysm
Conditions Associated with Saccular
Aneurysms
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Genetic
– Polycystic kidney disease (autosomal dominant)
– Defects in extracellular matrix proteins
e.g. Marfan syndrome…. Others
Non-genetic ?
– Coarctation of aorta
Predisposing conditions
– Hypertension
– Cigarette smoking (present in 54% of patients)
Clinical features of rupture
“Worst headache of my entire life” with
loss of consciousness
– 25-50% die at time of first rupture
– If survive, regain consciousness in
minutes
Clinical signs:
Headache, lethargy, photophobia, fever,
neck rigidity.
Focal deficit may be present depending
on site of hematoma
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Rupture results in
- Subarachnoid hemorrhage
- Parenchymal ± ventricular hemorrhage
- Bloody CSF (Xanthochromia)
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Mortality 35- 50% in acute phase, later
hydrocephalus & herniations
Sequelae:
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Acute:
– Vasospasm:
 Especially with blood at base of brain
 Some vasospasm occurs in about 50%
of cases ischemia & infarction
 Peak severity is at about 1 week
– Rebleeding in 30-50% of cases
 Risk is 20% in first 2 weeks
 Rebleed associated with mortality
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Chronic
Fibrosis of leptomeninges
May result in HYDROCEPHALUS
– If intraventricular hemorrhage 
obstruction of ventricles by blood 
acute hydrocephalus
– Fibrosis of leptomeninges 
communicating chronic hydrocephalus
Summary:
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Pr. Intracerebral hmg.  Hypertension
Subarachnoid hmg.  Berry Aneurysm
 Acute Complications
– Bleeding  Recovery ± Recurrence
 Infarction
 Death
– No bleeding  Incidental
 Space occupying &  ICP
 Chronic Complications
 Hydrocephalus
B- Vascular Malformations
Types of vascular malformations:
1)
2)
3)
4)
arteriovenous (AVM)
cavernous angioma
venous angioma
others
AVM is most likely to cause significant
hemorrhage.
1-Arteriovenous malformation
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Commonest congenital vascular abnormality
Abnormal connection between arteries & veins
More in males
Spontaneous hemorrhage between 10-30 years old
Involve vessels in subarachnoid & cerebrum
Gliotic brain tissue between vessels
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Clinical problems:
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Seizures, atypical migraine, hemorrhage, Risk of
rebleeding 1-4% per year with evidence of old &
recent hemorrhage ± calcification
Vascular Malformation
Vascular
Malformation
Vascular
Malformation
2- Cavernous Hemangioma
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Dilated thin-walled vascular channels
devoid of intervening brain tissue.
May cause seizures when subcortical.
Risk of hemorrhage 0.1-2.7% per
year, increases after first hemorrhage
HEMANGIOMA
3- Venous Angioma
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Aggregates of ectatic venous channels
brain, spinal cord & meninges
Progressive neurological syptoms
Low probability of hemorrhage
STROKE- SUMMARY
STROKE
ISCHEMIA
SYSTEMIC
HYPOTENSION
HEMORRHAGE
THROMBOSIS
EMBOLISM
Shock
Cardiac arrest
Arrhythmias
Border zone
(Water shed)
infarcts
SUBARACHNOID
INTRACEREBRAL
Ruptured aneurysm
AVM
Coagulopathy
SMALL VESSELS
LARGE VESSELS
FROM HEART
Arteriolosclerosis
(Lipohyalinosis)
Atherosclerosis
Dissection
Hypercoaguable state
Other vasculopathy
Fibromuscular dysplasia
Vasculitis
Valvular Disease
Rheumatic
Endocarditis
Mitral valve prolapse
Following MI
Atrial myxoma
Arrhythmias
Non-rheumatic atrial fibrillation
Sick sinus syndrome
Air emboli
Fat emboli
Foreign bodies
Lacunar infarcts
Sites:
Putamen
Caudate
Thalamus
Pons
Deep cerebellar white matter
Subcortical white matter
Note: embolic infarcts are often hemorrhagic
Hypertension
Vasculopathy
Amyloid angiopathy
Vasculitis
Coagulopathy
Drugs
Cocaine
Amphetamines
Hypertensive ICH
Sites: same as
lacunar infarcts
III-Epidural & Subdural Hemorrhage
These are usually TRAUMATIC
CENTRAL NERVOUS SYSTEM TRAUMA:
Result & morphology depend on:
 Penetrating or Blunt trauma Open or
Closed
 Mobile or immobile head at time of trauma
 Lesions at bony prominences e.g
– Frontal, orbital, temporal & occipital poles
– Spinal cord
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Edema may occur & worsen the condition
? skull fracture
“HAIRLINE”
“DEPRESSED”
or
“DISPLACED”
A- Parenchymal injury:
1- Concussion:
– Immediate and temporary disturbance of brain
function.
– No demonstrable lesion
– Signs: Amnesia, confusion, headache, visual
disturbances, nausea, vomiting, dizziness….
Then recovery
2- Contusions & lacerations of cortex:
– More on crests of gyri ±
– Intra parenchymal, subarachnoid hemorrhage
– Coup Contusion & Contrecoup contusion
Coup and contrecoup
contusions
 Coup lesions:
*Contusions immediately beneath and
associated with direct trauma
*Stationary head, no fracture, enough energy
to damage brain
 Contrecoup lesions:
* Contusions at a distance from & frequently
opposite to the point of trauma
* Often represent rotational & deceleration
injury, related to irregularities of the skull
opposite point of impact
Direction of Trauma
Multiple contusions involving the inferior surfaces of frontal lobes,
anterior temporal lobes, and cerebellum.
Else
Remote contusions are present on the inferior frontal surface of this
brain, with a yellow color
3- Intracerebral hemorrhage:
Cutting of brain vessels, high impact
4- Cerebral Edema: Occurs with and
without an obvious structural lesion
Note: Can occur without evidence of
hemorrhage
5- Diffuse Axonal Injury:
Stretching force & cutting of axons
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Diffuse Axonal Injury:
– Acceleration / Deceleration injury
– 50% of patients with post-traumatic coma
– Affect white matter (corpus callosum,
paraventricles, hippocampus…etc ) & at
junction of grey & white matter
– Characteristic asymmetrical axonal
swelling (Retraction Balls), micro –
hemorrhages, microglia, later gliosis
– Diffuse Hypoxic injury often occurs
– Post-traumatic dementia & vegetative
state.
Axonal retraction balls
B-Traumatic vascular injuries
1- Epidural Hemorrhage:
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Usually acute & accompanied by skull fracture
Seen in 3% of significant trauma
Rupture of middle meningeal artery
Rapid collection of blood (30 – 50ml → symptoms )
Mass effect  Dura & Brain compression
Rapid increase in ICP
Clinically: Patient has short LUCID interval
followed by rapid loss of consciousness
Fatal within 24 – 48 hrs. if untreated.
Epidural hematoma covering a portion of the dura.
Multiple small contusions are seen in the temporal lobe.
2- Subdural hemorrhage:
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Most occur with changed head velocity
e.g. boxers, battered baby & old age
More common than epidural
Disruption of Bridging Veins from brain to
dural sinuses, more over convexities
About 50% of acute are accompanied by
fracture.
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May be categorized based on the
interval between the hematoma and
the traumatic event
– Acute: within 3 days of trauma
– Subacute: between 3 days and 3 weeks
after trauma
– Chronic: develops after 3 weeks
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Acute:
- Clear history of trauma
- Frontoparietal is common
- Slow collection of clotted blood with
surrounding edema ICP
- Nonfatal cases  Chronic
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Chronic:
– Trauma often not recorded
– More in elderly with brain atrophy or
‘ Battered Baby Syndrome’
– Hematoma → Fluid filled cyst enclosed
by membrane may be resorbed, or
calcified
– Risk of rebleeding in first few months
– Clinically: confusion, dementia….etc
A. Large organizing subdural hematoma attached to the dura.
B. Coronal section of the brain showing compression of the
hemisphere underlying the hematoma.
Spinal cord trauma:
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Level of injury determines outcome
Lesions include contusions, fiber transection,
hemorrhagic necrosis  cystic foci in spinal
cord
Late effects: Ascending & descending
degeneration in nerve tracts & systemic
effects.
Effects depend on level:
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Cauda equina  pain, weakness of lower
limbs...
Thoracolumbar  Paraplegia
Cervical  Quadriplegia
Above C4  Paralysis of diaphragm
Result: Infections, genitourinary dysfunction
loss of bladder & anal control, bed sores ….
Perinatal Brain Injury
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May be intrauterine or during birth
Causes include:
– Hypoxic/Ischemic injury
– Germinal matrix hemorrhage
– Infections & Toxins
– Birth trauma
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May not be noticed at birth
Important cause of Cerebral Palsy 
Neurological motor deficits, e.g. spasticity,
dystonia, ataxia….
Intraventricular Hemorrhage from Germinal Matrix
Secondary Complications of
Trauma:
1- Diffuse brain edema, secondary
hemorrhage & herniations
2- Hypoxic brain damage
3- Infection
4- Fat embolism
5- Post-traumatic dementia
6- Persistent vegetative state
7- Epilepsy.