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Pathology of Nervous System

Dr. Bikash Puri

MVSc (Veterinary Pathology)

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Neuron and Galial response to injury

  • Cells of neuron swell, shrink, die, disappear or recover following injury.
  • Neuron is most sensitive to injury.
  • Response of neuron to Injury:
  • Neurons are highly sensitive and tends to react to disease in three ways.
    1. Acute Necrosis:
      • Usually associated with ischemia or acute toxicity or infectious disease
      • Neuron become shrunken and angular
      • Nucleous become pyknotic
      • Nissl substance (ER) in cytoplasm disappear (Chromatolysis) and cytoplasm becomes homogeneous bright eosinophilic appearance.
      • Later there is fragmentation of cell process, disruption of membrane and autolysis.

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Response of neurons to injury

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White arrow: Normal neuron

Black arrow: swollen and chromatolytic neuron

Arrowhead: shrunken, necrotic neuron

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Figure: Neuronal Necrosis (Acute), Cerebrum, Dog. A, Neuronal ischemia.

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Neuronal cell bodies of cerebralncortical laminae are red, angular, and shrunken (arrows), and their nuclei are contracted and dense. This lesion can be caused by neuronal ischemia.

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Figure: Central Chromatolysis, Neuron Cell Body, Dog

Affected neurons have eccentric nuclei and pale central cytoplasm with peripherally dispersed Nissl substance (arrows).

H&E stain.

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2) Degeneration of neuron

    • Associated with chronic disorder
    • It is characterized by contraction of cell body
    • Cytoplasma is more basophilic reflecting clumping and increased prominence of Nissl substance.
    • Presence of lipofuscin pigment in cytoplasm of degenerating neuron
    • Later, nucleous becomes pyknotic and fragments.
  • Axonal Reaction:
    • Occur when axon is injured
    • At first the neuron swells and loss its angularity
    • Nucleous is displaced to the periphery opposite to axon hillock
    • Nissl substance disappear (Central chromatolysis)
    • Upto this point changes is reversible.
    • Degeneration of myelin sheath.

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  1. Response of Astrocytes:
    • Act similar as fibroblast in other tissue
    • Acute injury astrocytes swells and cytoplasm become deeply eosinophilic and oxidative enzymes increases
    • These large swollen and reactive astrocytes are called gemistocytes.
    • In subacute and chronic cases there is increase proliferation of astrocytes with formation of new cells glial fibres (Gliosis/Scarring).
  2. Response of Oligodendrocytes:
    • In white matter oligodendrocytes proliferate in early process of demyelination where as they are scant in later stages
    • In gray matter, the oligodendrocytes swells in response to injury of Neuron.
    • In addition these cells accumulate around damaged neuron (Satellitosis)

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Gemistocytes (Gemistocytic Astrocytes), Cerebrum, Dog. A,

When astrocytes react to injury, initially by hypertrophy and later by the synthesis of increased glial filaments (astrogliosis), the nuclei enlarge and often the cell body, which is not normally visible in H&E-stained sections, will become visible. This type of reactive astrocyte is called a gemistocyte (plump astrocyte) (arrows). They occur in diseases in which there is alteration of intracellular and extracellular fluid balances or injury to the parenchyma, where healing will be by glial scarring (astrogliosis, e.g., to encapsulate a deep abscess or fill in a small area of dead space). H&E stain.

B, Gemistocytes (arrows) are identified by immunohistochemical staining (brown color) with antibody to glial fibrillary acid protein.

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  1. Microglial response to injury:
    • Act as the macrophages of CNS
    • Remain along the focus of the injury and phagocytized the dead tissue and engulf the lipids from degenerating myelin
    • Lipid laden macrophages are called Gitter cells.

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Notes: Oligodendrocytes is almost as sensitive as injury to neuron followed by astrocytes, microglial and capillaries.

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Figure: Gitter Cells, Cerebrum.

A; Macrophages (arrows) in the perivascular space have been recruited from the circulating monocytes.

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B,Previous region of necrosis, dog. The normal brain parenchyma has liquefied, and the debris has been ingested by macrophages (arrows), which has resulted in the cytoplasm of these cells becoming foamy. They are now designated as gitter cells or, simply, foamy macrophages.

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Correlation between function and location

  • Each locus within the nervous system correspond to different bodily process
  • So, clinical effect of lesion greatly depends on the location of the lesion with in the brain rather than its size.

Example:

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Cerebral cortex

Medulla oblongata

Dispersal of neuron over fairly large area

All neuron lies togother in relatively compact area

Thus, Small infract in frontal cortex may be of no apparent significance where as a lesion of the same size in medulla oblongata may cause instant death.

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Congenital Malformation

  1. Anencephaly:
    • Complete absence of entire brain
  2. Amyelia:
    • Absence of spinal cord
  3. Encephalocele:
    • Protusion of brain along with meninges through defect in cranium/skull.

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Congenital Malformation

  1. Prosencephaly:
    • Occurs due to failure of bilateral seperation of primitive single telecephalic cavity into two hemisphere.

Findings:

    • Presence of single central ventricles
    • Absence of longitudinal fissure, olfactory bulb and optic tracts
  • Hydrancencephaly:
    • Complete absence of cerebral hemisphere in carnium of normal size and formation.

4. Syringomycelia

    • Refer to tubular cavitation of spinal cord.

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Congenital Malformation

  1. Hydrocephalus:
    • Refer to abnormal accumulation of cerebrospinal fluid in cranial cavity.
    • It may be congenital or acquired.
    • It may be due to either----
          • Increase production of CSF
          • Obstruction of Normal flow of CSF or
          • Defective absorption of CSF.

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Congenital Malformation

  1. Normal Condtition:

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CSF is produce in Choroid plexuses and flow from lateral ventricles to

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Third ventricle

Fourth ventricle

Subarachnoid space

Foramen of Monro

Foramen of Sylvius

Foramen of Luschka

Obstruction in this normal flow leads to hydrocephalus.

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Gross findings

  1. Dilation of lateral and 3rd ventricles and CSF is under increased pressure.
  2. Parenchymal atrophy affecting chiefly the white matter and cerebral cortices.

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Figure: Congenital Hydrocephalus, Dog. The bone of the calvaria is thin and the fontanelles (arrows) are enlarged. The translucent membrane covering the fontanelles is periosteum.

Figure: Congenital Hydrocephalus, Brain, Calf. Note the symmetrically enlarged and dome-shaped calvaria

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Hydrocephalus.

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Dilated lateral ventricles seen in a coronal section through the mid thalamus.

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Cerebellar hypoplasia

  • Commonly observed in cats, dogs and calves.

Macroscopically:

    • cerebellum may be normal in size and appearance or it may be represented by a very small nubbin of tissue.

Microscopically:

    • There is loss of purkinje cells, the granular layer is narrowed and deficient in cells and molecular layer is usually normal.
    • In viral infection we can see intranuclear inclusion bodies.

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Figure: Cerebellar hypoplasia (cerebellar hypoplasia, top specimen; normal cat, bottom specimen)

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B, Note the folia of the cerebellum are hypoplastic and dysplastic with a reduced thickness of the molecular layer (arrows) and haphazardly organized and thinned granule cell layer (arrowheads). H&E stain.

C, The molecular layer (M) of the cerebellum is reduced in thickness and lacks the normal number of neuronal nuclei. The Purkinje cell layer (P) has large gaps between adjacent cells as the result of the loss of neuron cell bodies or the failure of neurons to migrate properly to form this layer. Note the retention of Purkinje cells (arrows) in the granule cell layer (G). The granule cell layer has significantly reduced numbers of neurons as shown by the lacknof nuclei. H&E stain. W, White matter.

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Meningitis

  • It is the inflammation of the covering of brain and spinal cord.
  • If only Dura is involved, it is called pachymeningitis, where as leptomeningitis refer to inflammation of pia-arachnoid.
  • It can be suppurative or non suppurative

Etiology:

    • Infectious – Viral (swine fever, Rabies); Bacterial (Leptospirosis); Parasitic (Multiceps)
    • Acute poisoning – (acute lead and copper poisoning)
    • Mechanical Injuries- fractures
    • Extension of infection from neighboring area (middle ear)

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Findings

Gross Findings:

    • Petechial hemorrhage in meninges
    • Meninges get thickened, congested and cloudy.
    • Presence of purulent exudate in fissure
    • Ventricular fluids is cloudy and flakes of exudate overlies the plexus as well as wall of ventricles.
  • Gross Findings:
    • Infiltration of neutrophils (in suppurative inflammation) while mononuclears (lymphocyte and macrophage) predominant in case of non-suppurative variety
    • Fibrosis in chronic cases

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Bacterial meningitis seen at #autopsy. Pus covers meninges (outer covering of brain). Pic: Morgan Blakely. #Pathology #neuropath

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Encephalitis/Myelitis/ Encepalomyelitis

  • Encephalitis is the inflammation of brain. Inflammation of spinal cord is called myelitis. However, the inflammation of both brain and spinal cord is called encephalomyelitis.
  • It may be both suppurative or non-suppurative

Etiology:

    • Infectious – Viral (swine fever, Rabies); Bacterial (Leptospirosis); Parasitic (Multiceps)
    • Acute poisoning – (Strychnine poisoning)
    • Mechanical Injuries- fractures, trauma

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Macroscopic findings

    • Congestion, haemorrhage and edema in brain
    • Presence of tiny abscess
    • Presence of localized area of softening

Microscopic findings:

    • Perivascular cuffing in virchow Robin space by lymphocytes.
    • Presence of intranuclear inclusion bodies
    • Necrosis of Neuron
    • Glisosis (Proliferation of astrocytes)
    • Satellitosis, neuronophagia
    • Pleocytosis- increase in number of white blood cells in CSF.
    • Tiny or micro -abscess in cerebrum
    • Lymphocytic infiltration is most prominent.

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Encephalomalacia

  • Malacia is the necrosis of the CNS.
      • Encephalomalacia ………………in brain.
      • Myelomalacia……………………in spinal cord.
      • Poliomalacia …………………….in Gray matter
      • Leukomalacia..…………………..in white matter

Etiology:

    • Deficiency : Cupper, thiamine, Vitamin E
    • Poison: Bracken fern poisoning, lead, mercury, salt poisoning, mycotoxin, enterotoxemia

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Fig: Encephalomalacia

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Bilateral discoloration and malacia (arrows) in a portion of the basal nuclei

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Gross findings

    • Necrosis in brain
    • Presence of soft, friable liquefied mass in brain.

Microscopic findings:

    • Liquefactive necrosis of brain parenchyma
    • Presence of gitter cells around the necrotic sites
    • Proliferation of microglial cells
    • Swelling of oligodendroglial cells
    • Gliosis- Proliferation of astrocytes
    • Proliferation of new capillaries
    • Pervascular cuffing.

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Fig: Chronic polioencephalomalacia, cerebral

cortex, cow.

Areas of microcavitation in the deep cortical

laminae next to the subcortical white matter are poorly stained (area between arrows) when compared with those of the normal superficial cortex (left). W, White matter.

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Spongiform Encephalopathy

  • It is characterized by the presence of vacules in grey/white matter.

Etiology:

    • Prion proteins
    • Scarpie in sheep
    • BSE in sheep

Macroscopic

    • No gross findings
    • Oedema and congestion of brain

Microscopic findings:

    • Vacuolation in white and grey matter.
    • Vacuoles are more extensive in medulla, pons and mid brain giving brain “Spongy form”

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Fig: Spongiform encephalopathy:

Neuronal cell bodies contain one or more discrete and/or coalescing clear vacuoles. There are no inflammatory cells in this disease.

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Changes associated with bacterial and viral diseases

Bacterial infection of CNS

    • Suppurative, lymphocytic and proliferative inflammation of CNS
    • Formation of microabscess in brain parenchyma due to embolism

Viral infection:

Gross findings:

    • No

Microscopic findings:

    • Progressive degeneration of neuron
    • Perivascular cuffing
    • Intranuclear inclusion bodies
    • Proliferation of microglial cells
    • Gliosis may be local.

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Injuries of CNS

  1. Concussion:
      • Sudden non fatal blow to the head.
      • There is loss of consciousness for short time
      • Due to sudden violent movement of CSF and blood.
  2. Laceration:
      • Injury in which there is disruption of architecture of nervous tissue
  3. Contusion:
      • Architecture of nervous tissue is retained but there is hemorrhage in meninges and around parenchymatous vessels.

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Neuritis�

  • Definition
    • Neuritis is inflammation of the peripheral nerve.
  • Etiology
    • Trauma
    • Viruses – Marek’s disease, Ranikhet disease.
    • Toxins – bacterial mostly. Neuritis occurs in infectious diseases as in strangles, protozoal – dourine, viral - rabies and distemper.
    • Chemical poisons – lead, mercury, arsenic, alcohol
    • Plant poisons – Lathyrus sativus.
    • Nutritional deficiency – deficiency of the members of vitamin B group.
    • Allergic factors.

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  • Gross pathology
    • More often no naked eye changes are noticed.
    • The nerve may be swollen, reddened, soft or flabby.
  • Histopathology
    • Microscopically, inflammation of the nerves is usually accompanied by degenerative changes.
    • Degenerative changes even leading to Wallerian degeneration are found.
    • Edema and infiltration by inflammatory cells of interstitial connective tissue can be seen.
    • The exudates may be serous (serous neuritis) or purulent (purulent neuritis). The latter variety may destroy the nerve completely.

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