PATHO CNS

• CNS


  • Disease
  • Etiology
  • Pathogenesis
  • Morphology
  • Clinical Features
  • Cellular Pathology of CNS
• Reaction of Neurons to Injury

  1. Acute process - depletion of O2, glucose, trauma

  2. Chronic process - accumulation of protein aggregates

  3. Acute neuronal injury (red neurons)

  4. Subacute & chronic neuronal injury (degeneration)

  5. Axonal reaction

  6. Neuronal inclusions
• Acute neuronal injury (red neurons)


  • Shrinkage of cell body, pyknosis, disappearance of nucleolus, loss of Nissl substance, intense eosinophilia of cytoplasm
  • Evident about 12-24 hours after acute CNS hypoxia/ischemia
• Subacute & chronic neuronal injury (degeneration)


  • Progressive disease of some duration
  • Characteristic histologic feature: cell loss, reactive gliosis
  • Early stage - difficult to detect, associated with reactive glial changes
• Axonal reaction


  • Cell body during regeneration of the axon
  • Increased protein synthesis → axonal sprouting
  • Enlargement, rounding up of cell body, peripheral displacement of nucleus, enlargement of nucleolus, central chromatolysis
• Neuronal inclusions


  • Lipofuscin, proteins, carbohydrate (aging)
  • Substrates or intermediates (disorders of metabolism)
  • Intranuclear Cowdry body (herpetic infection)
  • Cytoplasmic Negri body (Rabies)
  • Both nuclear & cytoplasmic inclusion (CMV)
  • Neurofibrillary tangle (Alzheimer disease)
  • Lewy bodies (Parkinson disease)
  • Abnormal vacuolization of perikaryon & neuronal cell processes (Creutzfeldt-Jakob disease)
• Reaction of Astrocytes to Injury

  1. Gliosis - hypertrophy & hyperplasia of astrocytes

  2. Gemistocytic astrocyte - bright pink, irregular swath around an eccentric nucleus cytoplasm, emerge numerous stout, ramifying processes

  3. Alzheimer type II astrocyte - large nucleus, pale-staining central chromatin, intranuclear glycogen droplet, prominent nuclear membrane & nucleolus

  4. Rosenthal fibers - thick, elongated, brightly eosinophilic, irregular structures within astrocytic processes

  5. Corpora amylacea - round, faintly basophilic, PAS+, concentrically lamellated, astrocytic end processes

  6. Lafora bodies - seen in cytoplasm of neurons (hepatocytes, myocytes)
• Astrocytes

  • Star-shaped, multipolar, branching cytoplasmic processes, contain GFAP
  • Metabolic buffers & detoxifiers
  • Foot processes - barrier functions between blood & CSF
• Gliosis


  • Most important histopathologic indicator of CNS injury regardless of etiology
  • Round to oval nuclei, evenly dispersed, pale chromatin, enlarge, vesicular, prominent nucleoli
• Reaction of Microglia to Injury

  Proliferating, rod cells (neurosyphilis), microglial nodules, neuronophagia
• Microglia


  • Mesoderm-derived phagocytic cells, resident macrophages of CNS
  • CR3 & CD68 surface markers
• Reaction of Other Glial Cells to Injury

  1. Injury or apoptosis of oligodendroglial cells → demyelinating disorders or leukodystrophies

  2. Multifocal leukoencephalopathy - viral inclusions in oligodendrocytes

  3. Multiple system atrophy - α-synuclein, glial cytoplasmic inclusions

  4. Inflammation → dilation of ventricular system, disruption of ependymal lining, proliferation of subependymal astrocytes → ependymal granulations

  5. CMV - ependymal injury & viral inclusions
• Oligodendrocytes


  • Wrap their cytoplasmic processes around axons, form myelin, myelinate numerous internodes → one-to-many
• Schwann cells


  • Myelinate peripheral nerves, one-to-one
• Ependymal cells

  • Ciliated columnar epithelial cells lining ventricles, do not have specific patterns of reaction
• Types of cerebral edema

  • Vasogenic edema
  • Cytotoxic edema
  • Interstitial edema (hydrocephalic edema)
• Vasogenic edema


  • BBB disruption → increased vascular permeability → increased extracellular fluid
  • Paucity of lymphatics → impairs resorption
• Cytotoxic edema


  • Hypoxic/ischemic insult, metabolic derangement → neuronal, glial, endothelial cell membrane injury → increase in intracellular fluid
• Interstitial edema (hydrocephalic edema)

  • Increase intravascular pressure → abnormal flow of fluid in lateral ventricles
• • Generalized edema: flattened gyri, narrowed sulci, compressed ventricular cavities
  • Brain expands → herniation
• Hydrocephalus

  Accumulation of excessive CSF within ventricular system
• Causes of hydrocephalus

  • Impaired flow & resorption of CSF (most cases)
  • Tumors of choroid plexus → overproduction (rare cause)
  • Mass in the 3rd ventricle → noncommunicating, obstructive hydrocephalus
  • Loss of brain parenchyma → compensatory increase → hydrocephalus ex vacuo
• Hydrocephalus


  • Enlargement of the entire ventricular system
  • Before closure of cranial suture in infancy → increase in head circumference
  • After closure of cranial suture → expansion of ventricles, increased ICP, without change in head circumference
• Raised ICP & herniation


  Displacement of brain tissue past rigid folds (falx, tentorium) or through openings in the skull because of increased ICP
• Types of brain herniation

  • Subfalcine (cingulate) herniation
  • Transtentorial (uncinate, mesial temporal) herniation
  • Tonsillar herniation
• Subfalcine (cingulate) herniation

  • Displaces cingulate gyrus under falx → compression of anterior cerebral artery
• Transtentorial (uncinate, mesial temporal) herniation


  • Medial aspect of temporal lobe compressed against free margin of tentorium → compress posterior cerebral artery → ischemic injury of the primary visual cortex
  • Large herniation → compress contralateral cerebral peduncle → ipsilateral hemiparesis (Kernohan notch)
• Tonsillar herniation

  • Displacement of cerebellar tonsils through the foramen of magnum → brainstem compression → compromises respiratory & cardiac centers
• • Duret hemorrhage - secondary hemorrhagic lesions in midbrain & pons
  • CN III compressed → pupillary dilation, impaired ipsilateral EOM
• Neural tube defects


  • Spinal dysraphism or spina bifida
  • Myelomeningocele (or meningomyelocele)
  • Encephalocele
  • Anencephaly
• Spinal dysraphism or spina bifida

  • Asymptomatic bone defect (spina bifida occulta)
  • Flattened, disorganized segment of spinal cord, associated meningeal outpouching
• Myelomeningocele (or meningomyelocele)


  • Extension of CNS tissue through a defect in vertebral column
  • Meningocele - meningeal extrusion
  • Most common in the lumbosacral region
  • Motor & sensory deficits in lower extremities, disturbances of bowel & bladder control
  • Complicated by superimposed infection
• Encephalocele


  • Defect in cranium → diverticulum of malformed brain tissue
  • Most often in posterior fossa
  • Cribriform plate in anterior fossa - misleadingly referred to as nasal glioma
• Anencephaly


  • Malformation of anterior end of neural tube with absence of most of brain & calvarium
  • Forebrain development is disrupted → area cerebrovasculosa
  • Posterior fossa may be spared
  • Area cerebrovasculosa - flattened remnant of disorganized brain tissue, admixed ependyma, choroid plexus, meningothelial cells
• • High concordance rate of anencephaly among monozygotic twins
  • Treatment: folate supplementation - must be given to women throughout their reproductive years
• Forebrain anomalies


  • Megalencephaly & microcephaly
  • Lissencephaly & agyria
  • Polymicrogyria
  • Neuronal heterotopias
  • Holoprosencephaly
  • Agenesis of corpus callosum
• Megalencephaly & microcephaly


  • Microcephaly - by far the more common of the two
  • Chromosome abnormalities, fetal alcohol syndrome, HIV-1 in utero → reduction in number of neurons that reach the neocortex → simplification of gyral folding
  • Small head circumference
• Lissencephaly & agyria


  • Reduction in the number of gyri
  • Extreme cases shows no gyral pattern → agyria
  • Type 1 - smooth surfaced
  • Type 2 - rough or cobblestoned
• Polymicrogyria


  • Localized tissue injury towards the end of migration
  • Genetic - bilateral & symmetric
  • Small, numerous, irregularly formed cerebral convolutions
  • Gray matter is composed of 4 layers (fewer), entrapment of apparent meningeal tissue at points of fusion
• Neuronal heterotopias


  • Collections of neurons in inappropriate locations along the pathway of migration
  • Mutations in filamin A → periventricular heterotopias
  • Mutations in DCX → lissencephaly in males, subcortical band heterotopias in females
  • Ventricular surface
  • Discrete nodules of neurons sitting in the subcortical white matter or complete ribbons that parody the overlying cortex