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Dr. Mohammed Alorjani, MD EBP
Pathology of Nervous System (I) -1 2016 Dr. Mohammed Alorjani, MD EBP
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Characteristic cellular features in the CNS
OUTLINE: Characteristic cellular features in the CNS General patterns of CNS cell pathology following various types of injury Consequences of ↑ CNS pressure Patterns of CNS vascular disease including trauma & perinatal CNS injuries Patterns of CNS infection 2
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Significant features in CNS Pathology
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Extremely susceptible to increased I.C.P.
Highly susceptible to ischemia & hypoxia Site of lesion may be more important than its nature Selective vulnerability of defined structures to disease processes Selective function of neurons in different sites Same process but different symptoms No regeneration gliosis not fibrosis
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Component cells of CNS Neurons Glial cells & fibers: Meninges:
Astrocyte Oligodendrocyte Ependymal cells Microglia Meninges: Meningothelial cells Connective tissue & BV
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Reactions of components to injury
Neurons: A- Acute injury: I- Necrosis: 12-24 hrs Irreversible ischemia/hypoxia: RED NEURONS with injured axons → axonal swelling → SPHEROIDS II- Apoptosis in development, aging…..
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Red Neurons in ischemic injury
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B - Chronic or subacute injury:
Degenerative diseases Neuronal loss & replacement by gliosis in progressive diseases, usually selective Neuronal processes may be thickened & tortuous (Dystrophic Neurites) e.g. Parkinson’s Disease, Alzheimer’s disease …….. etc.
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C -Axonal injury lead to:
Cell body swelling & Central Chromatolysis D- Inclusions: Nuclear or cytoplasmic e.g. viral infections E - Accumulations e.g. lipofuscin, complex lipids & abnormal proteins e.g. Tay Sach Disease …
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Chromatolysis
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Viral nuclear inclusions
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Rabies, cytoplasmic inclusions
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Lipid Accumulation
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Astrocytes: Respond by ↑number & size Commonest reactive change is Gliosis May lead to Fibrillary astrocytes Gemistocytes – Swollen reactive astrocytes with acidophilic cytoplasm (↑GFAP) Rosenthal fibers – Aggregates of thick eosinophilic astrocytic fibers, in old gliosis or some low grade glial tumors
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GFAP immunostain showing reactive astrocytes
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Arrows pointing at Gemistocytes
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Gemistocytes Rosenthal fibers
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Oligodendrocytes: Ependymal cells: - Deranged in demyelinating disease
- Synthesis & maintenance of myelin - Deranged in demyelinating disease - Inclusions in specific viral infections Ependymal cells: - Ependymal Granulations ?? - Inclusions characteristic of CMV
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Scavengers of the brain:
Microglia: Scavengers of the brain: Macrophages in infarction: (Gitter cells) Elongated cells in syphilis: (Rod cells) Aggregates of microglia around injured cells: (Microglial nodules) Aggregate around dead neurons: (Neuronophagia)
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Neuronophagia
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Microglia showing neuronophagia
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Increased Intracranial Pressure
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Definition: in CSF pressure > 15 mm. Hg
Manifestations: Papilledema & visual disturbances Nausea & vomiting Headache Neck stiffness Mental status changes Others
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Pathophysiology: Brain 70% , CSF 15% , Blood 15%
Intracranial compartments are balanced Expansion in any component is first compensated by in the rest i.e. CSF, blood , ventricular size If P. 15-20mm.Hg , compensation fails Displacements & Herniations Usually to opposite side of lesion contralateral ± ipsilateral symptoms
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TYPES OF HERNIATIONS:
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Types of herniation
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1- Subfalcine herniation
Herniation of Cingulate gyrus under falx cerebri into the subfalcine space Pressure on Anterior Cerebral Artery Cerebral infarction
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2- Transtentorial hernation
Uncinate herniation of medial temporal lobe through free margin of tentorium Pressure on PCA Occipital infarction 3rd.& 6th. Cranial Nerves. ipsilateral dilated pupil & impaired eye movement Cerebral peduncle compression on opposite side ipsilateral hemiparesis
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3- Tonsillar herniation
Herniation of cerebellar tonsil and medulla through foramen magnum BRAIN STEM !!! Pressure on respiratory & cardiac centers
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Cardiorespiratory failure & death DURET Hemorrhages:
Result : Brain stem compression & hemorrhage Acute obstruction CSF Cardiorespiratory failure & death DURET Hemorrhages: * Midline and paramedian brain stem hemorrhage secondary to brain herniation due to increased ICP above the tentorium from any cause. * Cause ? Laceration of penetrating veins and arteries supplying upper brain stem
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Duret hemorrhage
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Causes of Increased ICP
1- Cerebral Edema i - Vasogenic due topermeability with dysfunction of blood brain barrier Extracellular More in white matter Localized or Generalized Infarcts, contusions, tumors, abcesses… ii- Cytotoxic due to neuronal & glial injury Intracellular More in grey matter More in toxic & metabolic causes
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Flattened gyri often signify edema. Why
Flattened gyri often signify edema. Why? Ans: compression against the calvarium Dry flat gyri 36
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Sulci narrowed, blurred markings
Normal white matter Edematous white matter
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2- Infarction & Hemorrhage
3- Infections - Abscesses & meningitis 4- Tumors - Primary & Secondary 5- Trauma - especially in diffuse brain damage 6- Hydrocephalus
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CSF Flow Made in the ventricles Flows down aqueduct into 4th ventricle
Out into subarachnoid space Up to arachnoid granulations Back into the blood Obstructions in movement will lead to hydrocephalus CSF Flow
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CSF FLOW
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HYDROCEPHALUS Amount of CSF is balanced between its
generation & resorption. Otherwise, hydrocephalus develops. Excess CSF in ventricular system with enlarged ventricles, caused by I- resorption in inflammation & obstruction ii- Overproduction of CSF, e.g. in some tumors
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Hydrocephalus maybe acute rapid ICP
Chronic with compensation, mainly in children Large head, thin skull
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Fontanelle closure is the key factor whether hydrocephalus will result in any cranial enlargement
Fontanelle closure is the factor whether hydrocephalus will result in cranial enlargement 43
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Hydrocephalus. Magnetic resonance image of a child with communicating hydrocephalus, involving all ventricles.
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Hydrocephalus. Dilated lateral ventricles seen in a coronal section through the midthalamus.
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Types of Hydrocephalus:
1- Noncommunicating: Due to obstruction of CSF flow within the ventricles. Localized to site of obstruction.
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Due to a malformation or
acquired obstruction at foramina – Post-inflammatory Tumors Gliosis around aqueduct of Sylvius Intraventricular hemorrhage…etc
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2- Communicating: Impaired resorption. Generalized to all ventricles. - Post meningitis - Post subarachnoid hemorrhage 3- Normal pressure (ex vacuo) - Brain infarcts & Degenerative diseases - Compensatory CSF & Dilatation of ventricles.
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Congenital Malformations
May involve brain or spinal cord, causes ??? May be associated with mental retardation, or hydrocephalus …etc Include: Neural Tube defects e.g. Spina Bifida occulta, meningomyelocele, encephalocele, anencephaly… Forebrain defects Post. fossa defects e.g. Arnold Chiari Syndrome. Spinal cord defects.
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Arrow points at meningomyelocele
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ANENCEPHALY
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Thank you
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