patologi sistem saraf.edit
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PA sistem syarafTRANSCRIPT
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PATHOLOGY OF CENTRAL NERVOUS
SYSTEM
Yekti W. Widjono
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Central Nervous System
CONGENITAL
INFECTION
NEOPLASM
CEREBROVASCULAR
TRAUMA
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PRINTED BY FILAMEN '05Focal polymicrogyria: An incidental finding in a neurologically normal, 86-year-old man who died of chronic lung disease
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CNS Infections: Routes
1. Direct - skull fracture
2. Extension - sinuses and ears
3. Blood dissemination
4. Peripheral nerves (viruses)
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Some definitions
Pachymeningitis: inflammation of dura
Leptomeningitis (meningitis): infl of arachnoid
Cerebritis: infection of brain parenchyma by
agents other than viruses
Encephalitis: infl of parenchyma by viruses
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Acute meningitis: pathology
Bacterial: infiltration by neutrophils
Viral (aseptic): infiltration by lymphocytes
Fungus: predominantly infiltration by lymphocytes
Infiltration more common at base of brain than at
convexity
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Acute purulent meningitis: causative organisms
Neonatal: E. coli, B. strepto, L. monocytogenes
Children: H. influenzae, S. pneumoniae
Adolescents: N. meningitidis (meningococcus)
Adults: S. pneumoniae
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Acute bacterial meningitis: complications
Hydrocephalus, if not resolved
Pyocephalus (pus in ventricle)
Thrombosis of meningeal vessels and infarcts
Cerebritis and abscess
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Aseptic meningitis
Resolves spontaneously
No permanent sequela
Viruses:
Mumps, coxsackie, echo
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Chronic meningitis: pathology
Organisms: mycobacteria, fungus, spirochettes
Infiltration by lymphocytes
Granulomas: tuberculosis, fungus
Complications
fibrosis at base of brain hydrocephalus (more common than in bacterial
infection) Resolves spontaneously
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Aspergillosis
1. Opportunistic infection
2. Primary pulmonary infection
3. Cerebritis, abscess, infarctions
4. Vascular invasion
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Candidosis
1. Opportunistic infection
2. Primary GI infection
3. Microabscesses
4. Most common CNS fungal
infection at autopsy
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Cryptococcosis
1. Most common clinical CNS mycosis
2. Primary lung infection
3. Majority spontaneous infection
4. 30% opportunistic infections
5. Minimal inflammation
6. Multiple cysts: honey-comb appearance
7. India-ink exam of CSF
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Phycomycosis
1. Mucormycosis common
2. Associated with:
Diabetic ketoacidosis
Intravenous drug abuse
3. Acute fulminant disorder
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Bacterial Parenchymal Infections
Cerebritis
Brain abscess
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Brain Abscess: Sites
1. Direct extension:– large; single– frontal lobe in frontal sinusutis– temporal lobe in otitis and mastoiditis
2. Embolic:
small; multiple
MCA territory common
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Cerebral Abscess:Pathology
1. Suppurative cerebritis
2. Abscess formation
3. Granulation tissue
4. Fibrous capsule
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Encephalitis: Viral Tropism
1. Coxsackie, Echo, Mumps: Meninges
2. Herpes simplex: Temporal lobes
3. Herpes zoster (varicella): Posterior
ganglia
4. Poliomyelitis: Motor neurons
5. Rabies: Hippocampus, cerebellum
6. JC virus (PML): Oligodendrocytes
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Acute viral encephalitis: Pathology
Lymphocytic infiltration
Perivascular lymphocytes
Microglial nodules
Inclusion body
Necrosis
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Viral inclusion bodies: sites
HSV: intranuclear in neurons and oligodendrocytes
Rabies: intracytoplasmic in neurons
Cytomegalovirus: intranuclear or intracytoplasmic in neurons, glial cells, ependyma
PML: intranuclear in oligodendrocytes
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Slow Virus Infections: TypesConventional viruses:
1. Progressive multifocal leukoencephalopathy (PML)
PAPOVA viruses
2. Subacute sclerosing panencephalitis (SSPE)Measles virus
3. Progressive rubella encephalopathyRubella virus
Unconventional agents:Spongiform Encephalopathies (PRION
diseases)
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Pathologic States Associated with Progressive
Multifocal Leukoencephalopathy
Lymphoma
Leukemia
Sarcoidosis
Carcinomatosis
Miliary tuberculosis
Organ transplants (kidney)
AIDS
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Transmissible Spongiform Encephalopathies (PRION diseases)
Animals:
Scrapie - sheep, goat
Transmissible mink encephalopathy
Chronic wasting disease - mule deer, elk
Feline spongiform encephalopathy
Bovine spongiform encephalopathy (BSE)
Humans (subacute spongiform encephalopathy):
Kuru
Creutzfeldt-Jacob disease (CJD)
Gerstmann-Straussler Syndrome - Fam AD
Fatal familial insomnia - Fam AD
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Please read from the book on:
HIV infection (AIDS)
Cytomegalovirus
Toxoplasmosis
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BRAIN NEOPLASM
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General Considerations1. Comprise: 10% of all tumors
2. Most common childhood neoplasms
3. Peak incidence at 5th decade
4. Supratentorial tumors in adults
5. Infratentorial tumors in childhood
6. Different tumors in different ages
7. Primary tumors – infiltrative Metastatic - well-demarcated
8. Intraneural seeding occur, but no extraneural metastasis
9. Produce neurologic symptoms by size,location,invasiveness, and secondary effects
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Varieties of brain tumors
Meninges: meningioma, hemangiopericytoma
Astrocytes: astrocytoma (various types)
Oligodendrocytes: oligodendroglioma
Ventricles: ependymoma, choroid plexus papilloma,
colloid cyst
Vascular: hemangioblastoma
Primitive cells: germinoma, medulloblastoma,
neuroblastoma, pineoblastoma, retinoblastoma
Neuronal: ganglioglioma, gangliocytoma
Pituitary: adenoma, craniopharyngioma
Nerves: schwannoma, neuroblastoma
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Astrocytes: astrocytoma (various types)
Oligodendrocytes: oligodendroglioma
Ventricles: ependymoma, choroid plexus
papilloma, colloid cyst
GLIOMA
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Incidence of Intracranial Gliomas (All ages)
Glioblastomas
Astrocytomas
Ependymomas
Medulloblastomas
Oligodendrogliomas
Choroid plexus papillomas
Colloid cysts
55.0%
20.5%
6.0%
6.0%
5.0%
2.0%
2.0%
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Incidence of Primary IntraspinalIntramedullary Gliomas
Ependymomas
Astrocytomas (grades 1 and 2)
Glioblastomas (Astrocytomas
grades 3 and 4)
Oligodendrogliomas
Other tumors
63.0%
24.5%
7.5%
3.0%
2.0%
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Frequent Brain Tumors
Meningioma
Astrocytoma/glioblastoma
Oligodendroglioma
Ependymoma
Medulloblastoma
Schwannoma/neurofibroma
Phakomatosis
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Meningioma
Arachnoid cells origin
Attached to dura, subdural
Common sites: parasagittal (falx),
sphenoidridge, olfactory groove
Female:Male 3:2 or 2:1
Changes in cranium
Hyperostosis
Invasion
Microscopic: whorls and psammoma bodies
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Menoingioma
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Meningothelail whorls
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Psammoma bodies
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Gliomas
Astrocytes- astrocytomas
Fibrillary
Pilocytic
Oligodendrocytes- oligodendrogliomas
Ependyma- ependymomas
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Astrocytomas
Adult
Supratentorial
Solid
Malignant
Fibrillary
Childhood
Infratentorial
Cystic
Benign
Pilocytic
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Fibrillary Astrocytomas
Grossly solid
Common in cerebral hemispheres
Low grade in young, higher
grade in older
Grading
Astrocytoma (low grade)
Anaplastic astocytoma
Glioblastoma multiforme
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Fibrillary Astrocytoma: microscopic
Low grade- hypercellularity, pleomorphism
Anaplastic- as above plus mitosis, vascular
endothelial proliferation
Glioblastoma multiforme- as above plus
necrosis and pseudopalisades. Grossly
variegated appearance (multiforme)
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Astrocytoma
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Glioblastoma
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Glioblastoma - pseudopalisade
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Pilocytic AstrocytomaCommon in childhood
Most slow growing of the gliomas
Sites: cerebellum, around III V., optic
nerve
Grossly cystic with mural nodule
Microscopic
Elongated hair-like (pilo) elongated
cells
Rosenthal fibers
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Rosenthal fiber definition
Dense, eosinophilic fibers within
cytoplasmic processes of astrocytes.
Correspond to aggregate accumulation of
intermediate filaments in these processes.
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Pilocytic astrocytomaMural nodule
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Pilocytic astrocytoma
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Oligodendroglioma
Cells of origin: Oligodendrocytes
Common in cerebral hemispheres
Calcifications common among all
gliomas
Grades
Low grade
Anaplastic
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Oligodendroglioma
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Oligodendroglioma, calcifications
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Tumors in Ventricles
1. Ependyma: Ependymoma
2. Choroid Plexus: Papilloma
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Ependymomas
Arise from ependymal lining- ventricles
and central canal of spinal cord
Common in childhood
4th V. common in cerebrum
Most common tumor of spinal cord
parenchyma in adult
Microscopic
perivascular pseudorosettes
ependymal rosettes
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Ependymoma
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Ependymoma: perivascular pseudorosettes
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Embryonal tumors(Primitive neuroectodermal tumors)
Neuroblastoma - cerebral hemispheres
Neuroblastic (neuronal) differentiation
Medulloblastoma - cerebellum
Neuronal and glial differentiation
Ependymoblastoma – ventricles
Ependymal differentiation
Pineoblastoma- pineal region
Retinoblastic differentiation
All commonly known as Primitive
neuroectodermal tumor (PNET)
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Medulloblastoma
Origin: primitive neuroectodermal cells
Age: 1st decade of life. Most common
brain tumor at this age.
Site: vermis of cerebellum
May cause hydrocephalus
Subarachnoid dissemination
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Medulloblastoma
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Homer-Wright rosettes
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Histologic Patterns: definitions
Whorls: onion-skinning pattern of tumor cells
Psammoma bodies: laminated calcium
Pseudopalisading: lining up of the tumor cells
around a central necrotic area
Palisade: lining up of tumor cells around their own
cytoplasmic processes. No necrosis.
Pseudorosette: tumor cells around blood vessels,
cells equidistant from vessel walls.
Rosettes: tumor cells around central lumen or
fibrillary area of cellular processes
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Brain Tumors: Microscopic
Tumor Microscopic
Meningioma Whorls and psammoma bodies
Glioblastoma Pseudopalisades
Oligodendroglioma Mosaic/poached-egg
Ependymoma Perivascular pseudorosettes
Medulloblastoma Rosettes (Homer-Wright)
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Tumors of Nerve Rootsand Peripheral Nerves
1. Schwannoma
viii Cranial nerve (Acoustic sch.)
Spinal roots, posterior
Peripheral nerves
2. Neurofibroma
Spinal Roots, rare
Peripheral nerves
3. Malignant variants
Malignant peripheral nerve sheath tumor (MPNT)
Rare
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Peripheral nerve tumors
Schwannoma
Schwann cells
Compress the nerve trunk
Encapsulated
Easily resectable without nerve damage
Microscopic:
Antony A and B fibers
Verocay bodies
Neurofibroma
Schwann cells, neurites, fibroblasts
Fusiform and involves nerve trunk
Not encapsulated
Not resectable without sacrificing nerve
Micro- Intermingled cells with wavy nuclei
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AcousticSchwannoma
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Antony A
Antony B
Palisades
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Metastatic Brain TumorsMost common brain tumor in adults.
Common primary sites: melanoma, lung,
breast, GI tract, kidney.
Most are in cerebrum (MCA territory).
In gray-white junctions due to rich capillarity
Discrete, globoid, sharply demarcated tumors.
Amenable to surgical resection.
Single or multiple.
Brain edema frequent.
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Metastatic tumors
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Phakomatosis : definition
Phakos (Greek): lentil mole or freckle.
Neurologic abnormalities combined with
defects of skin or retina, explained by their
common ectodermal origin.
Involvement of visceral organs
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Phakomatosis(Neurocutaneous dysplasia)
1. Neurofibromatosis
(von Recklinghausen's dis.)
2. Tuberous Sclerosis
3. Sturge-Weber disease
(Encephalofacial Angiomatosis)
4. von Hippel-Lindau Disease
5. Neurocutaneous Melanosis
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Neurofibromatosis
1. Dominant inheritance
2. Multiple neurofibromas
Central - CNS
Peripheral nerves
3. Increased incidence of:
Meningioma
Glioma
Schwannoma - bilateral VIII N.
4. Cafe-au-lait (melanosis) in skin
5. Elephantiasis: increased connective
tissue
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Multiple neurofibromasCafé-au-lait spots
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Tuberous Sclerosis
1. Dominant inheritance
2. Clinical triad:– Seizures– mental retardation– adenoma sebaceum
3. Retinal hamartoma (phakoma)
4. Tubers in cerebral cortex
5. Subependymal giant cell astrocytoma
6. Hamartomas in other organs: heart, kidney
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Tubers
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Adenoma sebaceum
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CEREBROVASCULAR DISORDERS
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Cerebrovascular diseases involve circulatory disorders of brain secondary to alterations of structural integrity of blood vessels and/or alterations of blood pressure, and the complications thereof
Cerebrovascular disease is the third leading cause of death after heart disease and cancer in developed world.
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Some DefinitionsAnoxia - lack of oxygen
Ischemia - lack of circulation
Intracranial - enclosed by cranial bone (dura, arachnoid, brain)
Intracranial arteries - branches of circle of Willis in subarachnoid space (vertebro-basilar, ICA, MCA, ACA)
Intracerebral arteries/arterioles - within brain parenchyma
Intramedullary - in medulla or spinal cord
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Major Types of Cerebrovascular Disease
1. Anoxia/Ischemia
2. Intracranial hemorrhage
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Generalized (global)To entire brain
Focal (occlusive disease)To portion of brain
Ischemia
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Sequelae of severe global ischemia
Persistent vegetative state
severe neurological impairment and deep coma
Brain death
absence of perfusion, reflexes, respiration
brain stem damage
isoelectric (flat) EEG
“respirator brain”
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Conditions associated with hypotension
Myocardial infarction
Septic shock
GI hemorrhage
ruptured varices
bleeding ulcer
Ruptured aortic aneurysm
Others
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Arterial
Occlusio
n: Caus
es
1. Atherosclerosis
2. Thrombosis
3. Embolism
4. Vasospasm
5. Extrinsic compression
Anemic infarction
Hemorrhagic infarction
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Anemic and hemorrhagic infarctions vs hemorrhage
Anemic (pale, ischemic) infarction
no hemorrhage in infarcted area
Hemorrhagic infarction
petechial hemorrhage in infarcted area
no displacement of brain tissue
Hemorrhage
Bleeding is the primary event. Destroys and displaces the brain tissue
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Embolic Materials
1. Thrombus: from heart; aorta; carotid
2. Atheroma: aorta; carotid
3. Septic: endocarditis
Note: Most emboli go to middle cerebral artery.
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Intracranial Hemorrhage: Sites and Causes
1. Epidural
2. Subdural
3. Intracerebral
4. Subarachnoid
5. Mixed cerebral-subarachnoid
Trauma
Vascular (and trauma)
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1. Intracerebral
Hypertension
2. Subarachnoid
Berry aneurysm
3. Mixed cerebral-subarachnoid
Vascular malformations
Intracranial Hemorrhage: Main Causes
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Hypertensive Brain Hemorrhage: Sites
1. Putamen-Claustrum
2. Cerebral white matter
3. Thalamus
4. Pons
5. Cerebellum
55%
15
10
10
10
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Hypertensive Hemorrhage: Clinical
Presence of hypertension
Absence of prodroms
Headache frequent
Gradual or abrupt neurologic deficit
Deepening stupor or coma
Blood CSF (blood ruptures in ventricle or subarachnoid space)
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Intracranial vs intracerebral arteries
Intracranial arteries – atherosclerosis
Intracerebral arteries - hypertensive disease. No atherosclerosis.
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Vascular changes in hypertension
Accelerated atherogenesis in arteries
changes in arteriolesthickening and hyalinization of wall (arteriolosclerosis or arteriolar sclerosis)
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Vascular changes in hypertension
Accelerated atherogenesis in arteries
changes in arteriolesthickening and hyalinization of wall (arteriolosclerosis or arteriolar sclerosis)
necrosis of vessel wall (fibrinoid necrosis)
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1. Ruptured saccular (berry) aneurysm
2. Vascular malformations
3. Mycotic aneurysm (septic emboli)
4. Trauma
Causes of Subarachnoid Hemorrhage
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An aneurysm is
a dilatation of wall of an artery,
a vein or the heart.
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Aneurysms- Types
Saccular (berry)
Atherosclerotic (fusiform)
Mycotic (infections)
Dissecting (rare)
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Berry aneurysm Occur only at circle of Willis
Arise at points of branching
Saccular structure (sac-like, berry)
Devoid of media and elastic lamina
Multiple aneurysms common
Common sites: middle cerebral, internal carotid, anterior cerebral arteries
Most common cause of non-traumatic bleeding in the subarachnoid space
Increased incidence in patients with: inherited polycyctic kidney; neurofibromatosis; Marfan syndrome; fibromuscular dysplasia; coarction of aorta.
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Ruptured Aneurysm: Clinical
Sudden severe headache
Relative alertness following initial unconsciousness
No focal neurologic deficit
Bloody CSF
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Vascular Malformations of brain: Types
1. Arteriovenous malformation (AVM)
2. Cavernous angioma
3. Venous angioma
4. Capillary telangiectasis
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Arteriovenous malformation (AVM)
1. Abnormal thick arteries and veins
2. No intervening capillary channels
3. Arterio-venous fistula
4. Occur any part of the brain fromsurface to ventricle
5. Common type of malformationand cause of hemorrhage
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Cavernous (hem)angioma
1. Dilated veins
2. Veins intercommunicate
3. No brain tissue between the veins
4. Common type of malformationand cause of hemorrhage
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Venous (hem)angioma
1. Dilated veins
2. Do not communicate
3. Brain tissue present in between vessels
4. Not a common source of bleeding
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Capillary telangiectasis1. Dilated capillaries
2. Not a common source of bleeding
3. Mostly incidental finding at autopsy
Clinical manifastation of cerebrovascular diseases
• Strokeor
• Cerebrovascular accident (CVA)
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Stroke: variants1. Transient ischemic attacks (TIA)
deficiency resolves within 24 hours
2. Completed strokes
Causes of Stroke or CVA
1. Brain infarction
2. Brain hemorrhage
3. Subarachnoid hemorrhage
4. Miscellaneous
80%
10
7
3
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Stroke: Clinical differentiation
Prodromes Onset LOC CSF Blood Headache
Thrombosis TIA Gradual No No No
Embolism Cardiac Sudden No + / - + / -
Sub Hem No Sudden Initially + + + + + +
Intr Hem No Sudden Usual + + + + + Note: Lateralizing sign in all, except Subarachnoid hemorrhage.
LOC=loss of consciousness. Sub=subarachnoid. Intr=intracerebral
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Cerebral Edema: Types
1. Vasogenic: fluid in extracellular spacecommon type:infarction, hemorrhage,tumor, trauma
2. Cytotoxic : fluid in intracellular spacehypoxia, ketoacidosis
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Summary-1
Ischemia
Pale infarct(slow complete occlusion)
Hemorrhagic infarct(incomplete occlusion)
global (patterns of injury)
Focal vascular occlusion
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Summary-2
Hemorrhage
Subarachnoidberry aneurysm (sites, structure)
Intracerebralhypertensive disease(sites, arteriolar changes)
Mixedvascular malformations (types, structure)
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CENTRAL NERVOUS SYSTEM TRAUMA
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Important Considerations
Location of the lesion
Limited capacity to regenerate
Shape of the object
Force of the impact
Head’s motion
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Types of Injury
Open vs. closed
Penetrating vs. blunt
External vs. internal damage
Skull fractures
Parenchymal
Vascular
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ConcussionClinical syndrome
Change in momentum of the head
Instantaneous transient neurologic dysfunction,
loss of consciousness, loss of reflexes
Full neurologic recovery
Amnesia
No morphological changes
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Contusion
Bruising resulting from transmission of force
through other tissues
Vessel injury, tissue damage, edema
Crests of gyri
Inferior surfaces of frontal lobe, temporal
poles
Anywhere adjacent to fractures (fracture
contusion)
PRINTED BY FILAMEN '05Fronto-temporal contusions
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Remote fronto-temporalcontusions
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Base of frontal lobes
Contusions
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Intact brain tissue
Infarct
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Contusions
Lacerations
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Coup vs. Contrecoup
Coup lesion: At the site of
trauma, while head is still
Contrecoup: At the opposite
site of trauma, while head is
in motion
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Epidural Hematoma
Middle meningeal artery tear
by fracture
May occur without fracture in
children
Clinical presentation several
hours after injury (lucid
interval)
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Skull fracture
Fracture
Impression of middle meningealartery
Fro
nta
l
Occ
ipit
al
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Bone
DuraEpidural space
Subdural space
Epiduralhematoma
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Subdural Hematoma
Bridging vein tear by sudden
movement of brain
Slowly progressive neurologic
deterioration
Evolution:
Lysis of clot (1 week)
Early organization (2 weeks)
Hyalinized connective tissue (1-3
months)
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Bridging veinsReflected dura
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Subdural clot
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Subduralhematoma
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Subdural Hematoma
Multiple recurrent
hemorrhages from delicate
granulation tissue vessels
Chronic subdural hematoma
Removal of hematoma and
subdural membrane
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Chronicsubdural hematomas
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Capillary
Fibroblastic/endothelialproliferation
Fibrin clot
Subdural hematoma, chronic
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Internal carotidarteries
AneurysmSubarachnoidhemorrhage
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Post traumatic Syndromes
Post traumatic hydrocephalus
Post traumatic dementia,
“punch-drunk” syndrome
(dementia pugilistica)
Post traumatic epilepsy,
meningioma, infection
Post traumatic psychiatric
disorders
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Spinal Cord Trauma
Associated with bone injury
Progression of lesion due
to vascular injury
(ischemia) and
excitotoxicity
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DISORDERS OF MYELIN
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Overview
Primary myelin diseases (multiple sclerosis)
Diseases with secondary damage to myelin (HIV leukoencephalopathy, progressive multifocal leukoencephalopathy-PML,carbon monoxide poisoning)
Dysmyelinating diseases- leukodystrophies
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Multiple Sclerosis (MS)
Classical MS, Charcot type
Most common demyelinating disorder
Onset rare in childhood or >50 years of age
Male:Female = 1:2
Relapsing/remitting episodes, gradual deterioration
Clinical findings do not fit into a definitive anatomical distribution
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Multiple SclerosisEtiology unknown
Environmental:
Common in N. European & US, rare in orientals
15 years of age
Genetic:
15-20X risk in immediate relatives
HLA-DR2
Chemical
Viral
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Multiple Sclerosis
Autoimmune myelin destruction
Experimental allergic encephalomyelitis (EAE)
Increased cytokines, leukocyte adhesion molecules on endothelial cells
CD 4+ and CD 8+ T-cells, and macrophages
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Multiple Sclerosis
Most common locations: Optic nerve (unilateral visual impairment), spinal cord (motor/sensory impairment, bladder control problems), brain stem (cranial nerve deficits, ataxia)
Magnetic Resonance Imaging (MRI)
Cerebrospinal fluid
Increased immunoglobulins
Oligoclonal bands
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Ventricle
Plaques
Multiple sclerosis
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Plaque
Multiple sclerosisMidbrain
Aqueduct
Substantianigra
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Perivascular lymphocytes
Acute MS, myelin stain
Cellular lesion,myelin loss
Residual myelin
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Acute MS, silver stain
Perivascular lymphocytes
Preserved axons
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Chronic plaque, myelin stain
No inflammationMyelin loss,hypocellular
Myelin insurroundingtissues
Sharp border
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Chronic plaque, silver stain
Lesion border
Few preserved axons
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Other Primary Demyelinating Diseases
Acute Disseminated Encephalomyelitis (ADEM; postinfectious/ perivenous/ postvaccinial encephalomyelitis):
Acute, monophasic, children and adults, with headache, lethargy, coma, rapid progression, 20 % death
Acute Necrotizing Hemorrhagic Encephalomyelitis(ANHE;Weston-Hurst Disease):
After urinary tract infection, M. pneumoniae infection, in children and young adults
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ANHE
Numerous petechiaein WM
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ANHE, myelin stain
Capillaries
Perivascular myelinloss, inflammation