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Central nervous system pathology

Intro to CNS Patho.
Robbins and Cotran

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Central nervous system pathology

  1. 1. KRISTINE FAITH P. TABLIZO, RN MD-MPA pp. 1252-1263, Robbins & Cotran Pathologic Basis of Disease, 9th Ed.
  2. 2. Cellular Patho • Rxns of Neurons • Rxns of Astrocytes • Rxns of Microglia • Rxns of other Glial cells Cerebral Edema, Hydrocepha lus, Increased ICP, Herniation Malformations and Developmental Disorders • Neural tube defects • Forebrain anomalies • Posterior Fossa Anomalies • Syringomyelia and Hydromyelia Perinatal Brain Injury Trauma • Skull Fractures • Parenchymal Injuries • Concussion • Direct P. Injury • Diffuse Ax. Injury • Traumatic Vascular Injury • Epidural Hematoma • Subdural hematoma • Sequelae of Brain trauma • SC Injury
  3. 3. Reactions to Cellular Injury Neurons Astrocytes Microglia Other Glial Cells  Acute Neuronal Injury “RED NEURONS”  Cell body shrinkage  Nucleal PYKNOSIS  Nucleolus disappearance  Loss of Nissl Bodies- eosinophilia of cytoplasm  Gemistocytic astrocytes - Swollen reactive astrocyte  Nuclei vesicular w/ prominent nucleoli  Cytoplasm bright pink irregular area around an eccentric nucleus  Alzheimer type II astrocyte  Nucleus  2-3x larger,  pale staining chromatin  Intranuclear glycogen droplet  prominent nuclear membrane and nucleolus *in Chronic hyperammonemia Respond to injury by:  OLIGODENDROCYTES - Injury and apoptosis of which is afeature of acquired demyelinating disorders and leukodystrophies  NUCLEI- viral inclusions (progressive multifocal leukoencephalopathy)  Glial Cytoplasmic inclusions  α-synuclein composition -in MSA (mult. sys.atrophy) 1. Proliferation 2. Elongation of nuclei (rod cells) e.g Neurosyphilis 3. microglial nodules 4. Neuronophagia-  Subacute/Chronic* Injury “DEGENERATION” e.g. ALS, AD- ‘progressive’  Cell loss  Reactive Gliosis- proliferation or hypertrophy of glial cells
  4. 4. Reactions to Cellular Injury Neurons Astrocytes Microglia Other Glial Cells NEURONAL INCLUSIONS  AGING - intracytoplasmic accumulations of complex lipids (lipofuscin), proteins, or carbohydrates **Diorders of Metabolism-substrates or intermediates accumulate CYTOPLASMIC I.B.’s ROSENTHAL fibers  thick, elongated, brightly eosinophilic, irregular structures in astrocytic processes  αB –crystalline and hsp27- heat shock proteins, as well as ubiquitin  Glial tumor- pilocytic astrocytoma  Alexander dse. (leukodystrophy associated w/ mutations in the gene encoding GFAP) –in periventricular, perivascular, subpial regions Corpora amylacea (polyglucosan bodies) Round, faintly basophilic, PAS (+), concentrically lamellated structures, 5-50 um in diameter GLYCOSAMINOGLYCAN polymers, heat shock proteins and ubiquitin Degenerative change Lafora bodies- seen in cytoplasm of neurons* in myoclonic epilepsy *(also in hepatocytes, myocytes, other cells) -same composition as PGS bodies  VIRAL INFXNS a. intranuclear inclusions  COWDRY BODY- herpetic infxn b. Intracytoplasmic inclusions  NEGRI BODY-rabies b. both nucleus & cytoplasm  CMG virus infxn  DEGENERATIVE DISEASES -neuronal intracytoplasmic inclusions  Neurofibrillary tangles- AD  Lewy bodies- PD
  5. 5. Reactions to Cellular Injury Neurons Astrocytes Microglia Other Glial Cells  Axonal Reaction-change in cell body during regeneration - ↑ protein synthesis- axonal sprouting  enlargement and rounding up of the cell body  peripheral displacement of nucleus  Central chromatolysis (dispersion of Nissl substance from center to periphery) EPENDYMAL CELLS inflammation or marked dilation of ventricular system disruption of ependymal lining Proliferation of subependymal astrocytes Irregularities on ventricular surfaces (ependymal granulations)
  7. 7. CNS Cellular Patho NEGRI BODIES
  8. 8. CNS Cellular Patho COWDRY BODIES
  11. 11. CNS Cellular Patho ROSENTHAL FIBERS CORPORA AMYLACEA (Polyglucosan Bodies)
  12. 12. CNS Cellular Patho LAFORA BODIES
  14. 14. CNS Cellular Patho NEURONOPHAGIA
  15. 15.  MONRO-KELLIE HYPOTHESIS  states that the cranial compartment is incompressible, and the volume inside the cranium is a fixed volume. any increase in volume of one of the cranial constituents (blood, CSF, and brain tissue) must be compensated by a decrease in volume of another. Cerebral Edema, Hydrocephalus, Increased ICP, Herniation
  16. 16. Cerebral Edema, Hydrocephalus, Increased ICP, Herniation  CEREBRAL EDEMA (brain parenchymal edema)  Increased fluid leakage from blood vessels or injury to various cells in CNS  HYDROCEPHALUS  accumulation of excessive CSF w/in the ventricular system  impaired flow and resorption  overproduction- tumors of ch. Plexus  HERNIATION  displacement of brain tissue past rigid dural folds or through openings in the skull because of ↑ ICP
  17. 17. Cerebral Edema Vasogenic Edema Cytotoxic Edema Interstitial edema ↑ EXTRACELLULAR Fluid Caused by B-B-B disruption And ↑ vascular permeability ↑ INTRACELLULAR Fluid - 2° CELL MEMBRANE INURY HYDROCEPHALIC EDEMA -occurs sp. around LATERAL VENTRICLES ↑ Intravascular pressure abnormal flow of fluid from intraventricular CSF across ependymal lining to the periventricular white matter Localized- adjacent to inflammation or neoplasms * GENERALIZED HYPOXIC/ ISCHEMIC insult * METABOLIC Derangement affecting ionic gradient Generalized-  ff. ischemic injury; both vasogenic & interstitial components  Flattened gryi  Narrowed sulci  Compressed ventricular cavities  Herniation likely
  18. 18. Cerebral Edema Vasogenic Edema- Flattened gyri, narrowed sulci
  19. 19. Hydrocephalus  NORMAL CSF FLOW
  20. 20. Hydrocephalus  HYDROCEPHALUS before closure of sutures- Head enlargement  after closure- expansion of ventricles, ^ ICP w/o head enlargement
  21. 21. Hydrocephalus  HYDROCEPHALUS NON-COMMUNICATING COMMUNICATING ‘OBSTRUCTIVE hydrocephalus’  VS is obstructed, does not communicate w/ subarachnoid space  e.g. 3rd ventricle mass  Ventricular system is in communication with the subarachnoid space  Enlargement of entire ventricular system
  22. 22. Hydrocephalus  HYDROCEPHALUS
  23. 23. HerniationSubfalcine (cingulate) herniation Transtentorial (uncinate, mesial temporal) herniation Tonsillar Herniation Displaces cingulate gyrus under the falx. Medial aspect of temporal lobe compressed against the free margin of the tentorium Displacement of cerebellar tonsils through the foramen magnum Compromises CN III, and Posterior cerebral artery LIFE THREATENING- compression of brainstem (respiratory and cardiac centers) Compression of anterior cerebral artery and its branches Kernohan notch- compression in the contralateral cerebral peduncle; may result in hemiparesis of the side ipsilateral to the herniation Duret hemorrhages- linear of flame-shaped lesions usually in the middle and paramedian regions -due to distortion or tearing off penetrating veins and arteries supplying the upper brainstem
  24. 24. Herniation
  25. 25. Herniation Kernohan notch
  26. 26. Herniation Transtentorial herniation
  27. 27.  Neural tube defects  failure to close by a portion a the neural tube or reopening of a region of a tube after successful closure  account for most common CNS malformation  most common NTD– SC involvement  frequency varies among ethnic groups  high concordance rate among monozygotic twins  risk factor: folate deficiency during 1st several weeks of gestation Malformations and Devt’al Disorders
  28. 28. Malformations and Devt’al Disorders Neural Tube Defects Spina Bifida/ spinal dysraphism Meningomyelocele/ Myelomeningocele Encephalocele (Cranium bifidum) Anencephaly SPINA BIFIDA OCCULTA - asymptomatic bony defect - Mildest form - Missing spinous process Extension of CNS tissue through a defect in the vertebral column Diverticulum of malformed brain tissue extending through a defect in the cranium Malformation of the anterior end of the NT, with absence of most of the brain and calvarium sacral region Most often in the posterior fossa *Area Cerebrovasculosa- flattened remnant of disorganized brain tissue w/ admixed ependyma, choroid plexus, and meningothelial cells *MENINGOCELE -meningeal outpouching only Lower Motor and sensory deficits ; bladder and bowel control deficits May also occur through the cribiform plate in the anterior fossa– “nasal glioma” Risk for superimposed infections- thin overlying skin
  29. 29. Malformations and Devt’al Disorders
  30. 30. Malformations and Devt’al Disorders
  31. 31. Malformations and Devt’al Disorders "area cerebrovasculosa" -scattered primitive neuroglial tissue elements within an irregular vascular proliferation
  32. 32.  Forebrain Anomalies  Disruption in proper orchestration of progenitor cell proliferation and migration to the developing cortex  single gene mutations, larger scale genetic alterations, or exogenous factors  Alteration in the size, shape, and organization of the brain  Overall, the earlier a malformation occurs, the more severe the morphologic and Malformations and Devt’al Disorders
  33. 33. Malformations and Devt’al Disorders Forebrain Anomalies Megalencephaly Abnormally large volume of brain Lissencephaly Polymicrogyria - decreased # of gyri AGYRIA- absence of gyri in extreme cases TYPE I-smooth surfaced -mutations disrupting signaling for migration and cytoskeletal motor proteins TYPE 2- rough or cobblestoned - Disruption in “stop signal for migration Small unusually numerous irregularly formed cerebral convolutions Causes: -localized tissue injury toward the end of neuronal migration - Genetically determined-- bilateral and symmetric Microencephaly Abnormally small volume of brain -more common than megalo- - chromosome abnormalities, FAS, HIV-1 in utero -simplification of gyral folds -reduction in # of neurons that reach neocortex
  34. 34. Malformations and Devt’al DisordersCont….. Forebrain Anomalies Neuronal Heterotopias Holoprocencephaly Agenesis of Corpus callosum -migrational disorders commonly associated w/ epilepsy -presence of neurons in inappropriate locations along the pathway or migration -incomplete separation of the cerebral hemispheres across the midline -associated with trisomy 13 and other genetic syndromes - Mutations in sonic hedgehog signaling pathway • Severe forms- midline facial abnormalities, including cyclopia • less severe variants-(arrhinencephaly) absence of the olfactory cranial nerves and related structures -relatively common -misshapen lateral ventricles “bat-wing deformity” in radiologic imaging - commonly associated with mental retardation - may occur in clinically normal individuals
  35. 35. Malformations and Devt’al Disorders  Periventricular heterotropia- mutations-gene encoding filamin A (an actin-binding protein responsible for assembly of complex meshworks of filaments) on the X chromosome • mutant allele- causes male lethality  Doublecortin (DCX)- microtubule-associated protein  on X chromosome • mutations result in lissencephaly in males • in subcortical band heterotopias in females.
  36. 36. Malformations and Devt’al Disorders
  37. 37. Malformations and Devt’al Disorders Polymicrogyria
  38. 38. Malformations and Devt’al Disorders Holoprosencephaly
  39. 39. Malformations and Devt’al Disorders Bat-wing or bull-horn sign
  40. 40.  Posterior Fossa Anomalies  BRAINSTEM and CEREBELLUM involvement  may be accompanied with morphologic changes in other areas of the brain Malformations and Devt’al Disorders
  41. 41. Malformations and Devt’al Disorders Posterior Fossa Anomalies Arnold-Chiari Malformation (Chiari Type II) • small posterior fossa • misshapen midline cerebellum with downward displacement of vermis and medulla through the foramen magnum • symptomatic *May present w/ hydrocephalus (obstruction of IV ventricle) and a lumbar myelomeningocele Chiari type I malformation • Mostly asymptomatic; less severe • More common • Low lying cerebellar tonsils extend down the vertebral canal • SSx appear with compression
  42. 42. Malformations and Devt’al DisordersCont… Posterior Fossa Anomalies Dandy-Walker Malformation • Enlarged posterior fossa. • Absent cerebellar vermis* (or rudimentary form in the anterior portion) • Large midline cyst* (in place of vermis) lined by ependyma Other common associated findings: • Dysplasias of brainstem nuclei • Failure of Foramen of Magendie and Luschka to dilate Joubert Syndrome • Hypoplasia of cerebellar vermis with apparent elongation of superior cerebellar peduncles and altered shape of the brainstem • ‘molar tooth sign’ Cause: mutations in genes encoding components of the primary (non-motile) cilium cellular signaling
  43. 43. Malformations and Devt’al Disorders
  44. 44. Malformations and Devt’al Disorders
  45. 45. Malformations and Devt’al Disorders JOUBERT SYNDROME “MOLAR TOOTH SIGN”
  46. 46. Malformations and Devt’al Disorders Hydromyelia Syringomyelia, syrinx Syringobulbia Expansion of the ependymal-lined central canal of the cord Formation of fluid-filled cleft-like cavity in the inner portion of the cord Extension of syringomyelia to the brainstem• Seen in Chiari malformations • Associated w/ intraspinal tumors Distinctive SSx: • Isolated loss of pain and temperature sensation in the upper extremities HISTOLOGIC APPEARANCE: • W/ destruction of adjacent gray and white matter • Surrounded by dense feltwork of reactive gliosis EPIDEMIOLOGY: • Manifests in 2nd or 3rd decade
  47. 47. Malformations and Devt’al Disorders Hydromyelia
  48. 48. Malformations and Devt’al Disorders
  49. 49.  Brain injury occurring in the perinatal period  important cause of childhood-onset neurologic disability Perinatal Brain Injury
  50. 50.  CEREBRAL PALSY*- nonprogressive neurologic motor deficit attributable to insults during prenatal and perinatal periods COMBINATIONS: Spasticity Dystonia Perinatal Brain Injury Ataxia/ athetosis Paresis *s/sx may not apparent at birth
  51. 51. Perinatal Brain Injury
  52. 52. Perinatal Brain Injury Destructive lesions associated w/ Cerebral Palsy  Periventricular leukomalacia- white matter brain injury esp. in premature infants  chalky yellow plaques w/ discrete regions of white matter necrosis and calcification  Multicystic encephalopathy- both gray and white matter involved large destructive cystic lesions d/t extensive ischemic damage
  53. 53. Perinatal Brain Injury Destructive lesions associated w/ Cerebral Palsy  Ulegyria  thinned-out gliotic gyri  status marmoratus  marble-like appearance of the deep nuclei d/t aberrant and irregular myelinization
  54. 54. Perinatal Brain Injury
  55. 55. Perinatal Brain Injury STATUS MARMORATUS
  56. 56. Head injuries by physical forces  SKULL FRACTURES  PARENCHYMAL INJURY  VASCULAR INJURY * all 3 may coexist Trauma CNS TRAUMA MAJOR DETERMINAN  ANATOMIC location of LESION  LIMITED CAPACITY of brain for rep i.e. Several cubic mm of brain pare injury • Frontal lobe- clinically silent • SC- severely disabling • Brainstem- fatal
  57. 57. SKULL FRACTURES  displaced skull fracture - bone displaced into the cranial cavity by a distance greater than the bone’s thickness  thickness of the cranial bones varies Diastatic fractures - cross sutures Trauma
  58. 58. SKULL FRACTURES (PRINCIPLES) Pattern of falls  Fall while awake- site of impact often the occipital portion of the skull  Fall following unconsciousness- frontal impact kinetic energy is dissipated at a fused suture Fracture lines of subsequent injuries do not extend across those of prior injury with multiple points of impact or repeated blows to the head Trauma
  59. 59. Basal skull fracture  typically follows impact to occiput or sides of the head  lower cranial nerves or cervicomedullary region symptoms  orbital or mastoid hematomas* distant from the point of impact  CSF rhinorrhea/ otorrhea, meningitis Trauma
  60. 60. Trauma
  61. 61. Trauma Parenchymal Injuries Concussion Direct Parenchymal Injury Diffuse axonal injury • mild traumatic brain injury with a transient loss of brain fx • commonly d/t change in the momentum of the head (against a rigid surface) • Instantaneous onset of transient neurologic dysfunction • Usually without parenchymal changes a. CONTUSION- bruise in the brain caused by blunt trauma • coup and contrecoup injuries -head is mobile at the time of impact b. LACERATION- caused by penetration of an object and tearing of tissue • injury to axons at nodes of Ranvier with impairment of axoplasmic flow • d/t acceleration/ deceleration even in absence of impact • coma after trauma without evidence of direct parenchymal injuries
  62. 62. Trauma Cont… MORPHOLOGIC CHANGES/ CHARACTERISTICS Concussion Direct Parenchymal Injury Diffuse axonal injury • Acute contusion- hemorrhage of brain tissue in a wedge-shaped area • Subacute contusion – necrosis/ liquefaction • Remote contusion- yellowish depressed area of cortex "plaque jaune*” • (early)  edema and hemorrhage often pericapillary • (next few hrs)  Blood extravasation • (~24 hours) SSx of neuronal rxn to damage • old contusions- gliosis and residual hemosiderin- laden macrophages* • often asymmetric appreciable in the white matter • Ag impregnation or immunoperoxidase stains (for amyloid/ a synuclein) • predilection for the corpus callosum, periventricular white matter, and hippocampus, cerebral and cerebellar peduncles
  63. 63. Trauma
  64. 64. Trauma • PLAQUE JAUNE • Old traumatic lesions depressed, retracted, yellowish brown patches involving the crests of gyri • Common at the sites of contrecoup injuries (inferior frontal cortex, temporal and occipital poles) • Can become an epileptic foci
  65. 65. Trauma
  66. 66. Trauma TRAUMATIC VASCULAR INJURY direct trauma and disruption vessel wall hemorrhage  epidural, subdural, subarachnoid, intraparenchymal or combination  epidural and subdural hemorrhages- rare in non trauma setting
  67. 67. Trauma
  68. 68. Trauma
  69. 69. Trauma Epidural Hemorrhage  associated with skull fracture  tearing of dural arteries-- common: middle meningeal artery  accumulates slowly --("talk and die syndrome")  smooth inner contour hematoma  does not cross suture line  may expand rapidly neurosx emergency requiring prompt drainage  if not promptly evacuated  cerebral herniation
  70. 70. Trauma Subarachnoid hemorrhage  Common cause: ruptured berry aneurysm  sudden ("thunderclap") headache, nuchal rigidity, neurological deficits on one side, and stupor  blood in the ventricles, sulci, and cisterns
  71. 71. Trauma  Intracerebral (intraparenchymal) hemorrhage Common cause: HTN common area: basal ganglia, cerebellum, pons, centrum semiovale  SSx: severe headache, frequent nausea/vomiting, steady progression of symptoms over 1 5-20 minutes and coma Other causes: vascular malformations (sp. AV malformations), cerebral amyloid angiopathy, neoplasms,
  72. 72. Trauma Subdural hemorrhage  rupture of bridging veins* , may cross suture lines  Predisposing conditions: Brain atrophy(due simply to aging)- stretching of veins  infants- thin-walled bridging veins  abnormal hemostasis  SSx: headache, drowsiness, focal neurological deficits, and sometimes dementia
  73. 73. Trauma Subdural hemorrhage (Clinical Features)  Slowly progressive neurologic deterioration  manifests within 48 hours of injury  most common over lateral aspects of cerebral hemispheres  often nonlocalizing manifestations: headache and confusion  Tx: evacuation of blood clot and associated organizing tissue
  74. 74. Trauma  ACUTE Subdural hematoma (GROSS)  freshly clotted blood along brain surface without extension into sulci  subarachnoid space clear  venous bleeding, usually self-limited  organization of hematoma:  Lysis of the clot (about 1 week)*  Growth of fibroblasts from the dural surface (2 weeks)  Early development of hyalinized connective
  75. 75. Trauma  ACUTE Subdural hematoma  organized hematoma*-firmly attached to the inner surface of the dura by ingrowing fibrous tissue  multiple recurrent episodes of bleeding in chronic subdural hematomas (d/t thin-walled vessels of the granulation tissue)  repeat bleeding risk: greatest in the 1st few months after initial hemorrhage
  76. 76. Trauma
  77. 77. Trauma
  78. 78. Trauma
  79. 79. Trauma Subaracnoid hemorrhage
  80. 80. Trauma Intraparenchymal Hemorrhage
  81. 81.  Sequelae of Brain Trauma  neurologic syndromes that may manifest months or years after brain trauma of any cause • Posttraumatic hydrocephalus - largely due to obstruction from hemorrhage Other important sequelae of brain trauma: • posttraumatic epilepsy, •risk of infection, and •psychiatric disorders. Trauma
  82. 82. Chronic traumatic encephalopathy (CTE)- “dementia pugilistica” – dementing illness that develops after repeated head trauma  atrophic  with enlarged ventricles  w/ accumulation of tau-containing neurofibrillary tangles in a characteristic pattern involving superficial frontal and temporal lobe cortex  Boxers, military personnel, athletes Trauma
  83. 83. Trauma
  84. 84.  Spinal Cord Injury  associated w/ the transient or permanent displacement of vertebral column  Lesion involvement and manifestation  thoracic segments or below - paraplegia  cervical segments - tetraplegia  above C4 - respiratory arrest Trauma
  85. 85. SOURCES:  Robbins & Cotran Pathologic Basis of Disease, 9th Ed.  KAPLAN USMLE Reviewer 2013 (Pathology)  Pathology: a Color Atlas by Damjanov & Linder  Google images