CNS

• Cellular Pathology of the CNS


  • Reactions of Neurons to Injury
  • Reactions of Astrocytes to Injury
  • Reactions of Microglia to Injury
  • Reactions of Other Glial Cells to Injury

  
• Acute Neuronal Injury (Red Neurons)


  Changes seen following acute CNS hypoxia/ischemia, severe hypoglycemia, and other acute insults
• Subacute & Chronic Neuronal Injury (Degeneration)


  Neuronal death that occurs as a result of a progressive disease
• Axonal Reaction


  Observed in the cell body during regeneration of the axon
• Neuronal Inclusions


  • Lipofuscin
  • Proteins
  • Carbohydrates
  • Viral inclusions bodies
  • Neurofibrillary tangles of Alzheimer disease
  • Lewy bodies of Parkinson disease
  • Abnormal vacuolization of the perikaryon and neuronal cell processes in the neuropil (Creutzfeldt-Jakob disease)
• Wallerian Degeneration


  Degeneration of axons after disruption of nerve fibers
• Gliosis (astrogliosis)


  Most important histopathologic marker, characterized by hypertrophy and hyperplasia of astrocytes
• Acute Astrocytic Injury


  Manifested by cellular swelling, Alzheimer type II astrocyte
• Astrocytic Injury With Formation of Cytoplasmic Inclusion Bodies


  Rosenthal fiber, Corpora amylacea or polyglucosan bodies, Lafora bodies
• Reactions of Microglia to Injury


  Proliferating, developing elongated nuclei, forming microgial nodules, congregating around cell bodies of dying neurons (neuronophagia)
• Reactions of Oligodendrocytes to Injury


  Injury or apoptosis of oligodendrocytes is a feature of acquired demyelinating disorders and leukodystrophies, oligodendroglial nuclei may harbor viral inclusions in progressive multifocal leukoencephalopathy (PML), glial cytoplasmic inclusions primarily composed of α-synuclein, seen in multiple system atrophy (MSA)
• Reactions of Ependymal Cells to Injury


  Inflammation or marked dilation of the ventricular system-disruption of ependymal lining + proliferation of subependymal astrocytes ependymal granulations, CMV infection- extensive ependymal injury + viral inclusions in ependymal cells
• Causes of Raised ICP


  • Generalized brain edema
  • Increased CSF volume
  • Focally expanding mass lesions

  
• Cerebral (Brain Parenchymal) Edema


  Result of increased fluid leakage from blood vessels and injury to various cells of the CNS

  
• Two Main Pathways of Edema Formation in the Brain

  • Vasogenic Edema
  • Cytotoxic Edema

  
• Hydrocephalus


  Accumulation of excessive CSF within the ventricular system
• Types of Hydrocephalus


  • Non-Communicating or Obstructive
  • Communicating
  • Hydrocephalus Ex Vacuo
• Raised ICP and Herniation


  Displacement of brain tissue past rigid dural folds (falx and tentorium) or through openings in the skull because of increased ICP

  
• Location of Herniations


  • Subfalcine (cingulate) herniation
  • Transtentorial (uncal, mesial temporal) herniation
  • Tonsillar herniation
• Neural Tube Defects


  • Anencephaly
  • Encephalocele
  • Myelomeningocele (Meningomyelocole)
  • Spinal Dysraphism (Spina Bifida)
• Area cerebrovasculosa


  Flattened remnant of disorganized brain tissue with admixed ependyma, choroid plexus and meningothelial cells

  
• Admixed ependyma


  Type of neural cell

  
• Choroid plexus


  Type of neural cell
• Meningothelial cells


  Type of neural cell
• Types of Neural Tube Defects


  • Anencephaly
  • Encephalocele
  • Myelomeningocele (Meningomyelocole)
  • Spinal Dysraphism (Spina Bifida)
• Anencephaly


  • Malformation of the anterior end of the neural tube
  • Absence of most of the brain and calvarium
  • Posterior fossa structures may be spared
  • Descending tracts associated with disrupted structures are absent

  
• Encephalocele


  • Extrusion of malformed brain tissue through a midline defect in the cranium (most often in the occiput)
  • Nasofrontal variants involving the orbit, ethmoid, or cribriform plate (mistaken as nasal glioma)

  
• Myelomeningocele (Meningomyelocole)


  • Extension of CNS tissue through a defect in the vertebral column
  • Meningocele- only a meningeal extrusion
  • Occur most commonly in lumbosacral region
  • Motor and sensory deficits in the lower extremities and disturbances of bowel and bladder control
  • Often complicated by superimposed infection of the cord due to defective barrier function
• Spinal Dysraphism (Spina Bifida)


  • Most common neural tube defects
  • May be an asymptomatic bony defect (spina bifida occulta) or a severe malformation with associated with meningeal outpouching
• Overall recurrence rate for NTD in subsequent pregnancies estimated at 4-5%
• Folate deficiency during the first several weeks of gestation is a well-established risk factor
• Folate can lower the risk of NTD, but because neural tube closure is normally complete by day 28 (before most pregnancies are recognized), it must be given to women throughout their reproductive years to be fully effective
• Folate deficiency: effects on DNA methylation (important epigenetic mode of gene regulation)
• Abnormalities in the generation and migration of neurons result in malformations of the forebrain
• Total number of neurons is determined by fraction of proliferating cells that undergo transition into migration cells
• Migration of neurons from the germinal matrix to the cerebral cortex


  1. Radial migration- for progenitor cells destined to become excitatory neurons

  2. Tangential migration- for those that will become inhibitory interneurons
• Many patterns are caused by mutations in genes that are required for proper cerebral development
• Anatomic Patterns of Forebrain Anomalies


  • Abnormal Brain Volume
  • Lissencephaly
  • Polymicrogyria
  • Neuronal Heterotopias
  • Holoprosencephaly
  • Agenesis of Corpus Callosum

  
• Abnormal Brain Volume


  • Megalocephaly- abnormally large
  • Microcephaly- abnormally small; more common; small head circumference
  • Associated with chromosome abnormalities, fetal alcohol syndrome, and viral infection acquired in utero (HIV-1 or Zika virus)

  
• Lissencephaly


  • Reduction in the number of gyri, which may show no gyral pattern (agyria)
  • Smooth-surface form (type 1)
  • Rough- or cobblestone-surface form (type 2)