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()Map NERVOUS SYSTEM (Map)



Introduction

  • Although the CNS is well protected, its defences against organisms that have already invaded are less well developed. This is due to:
    1. Minimal antibody production
    2. Cerebrospinal fluid providing a good culture medium for invading organisms.
    3. Inflammatory cell, antibody and drug entry to the CNS being impeded by the blood-brain barrier.

Classification of Inflammation

  • CNS inflammation may manifest as encephalitis or meningitis.
    • These often co-exist.
  • The aetiology CNS inflammation may be:
    • Infectious
      • Bacteria
      • Fungi
      • Protozoa
      • Viruses or non-infectious.
      • Infectious agents vary geographically.
    • Non-infectious
      • No infectious cause can be found in 60% of meningitis cases.
  • Inflammation may also be broadly classified based on the nature of the exudate present.
    • Fibrinous
      • Caused by bacteria infection (including Mycoplasma).
    • Suppurative
      • Caused by bacteria and fungi.
    • Granulomatous
      • Caused by bacteria or fungi.
    • Lymphoplasmacytic
      • Caused by viruses.
    • Haemorrhagic
      • This is rare.
      • Usually associated with septicemia or infarcts.

Routes of Entry

  • CNS inflammation is usually the result of infection.
    • This may be caused by:
      • Bacteria
      • Fungi
      • Protozoa
      • Viruses
  • Organisms must first enter the CNS in order to establish infection.
    • There are several routes of entry that allow this:
      1. Haematogenous entry
        • This is the most common route.
      2. Entry via the peripheral nerves
        • Organisms track within the axoplasm of axons.
        • For example, Listeria monocytogenes.
      3. Penetrating trauma
        • For example, dehorning wounds, skull fracture or tail docking.
      4. Direct spread of infection
        • From the nasal cavity, middle ear or paranasal sinuses.

Localisation of Infectious Organisms

  • After entry, organisms may establish in one or more of four main areas:
    1. Epidural space
      • Infection tends to manifest as abscess formation.
    2. Subdural space
      • Manifests as abscess formation.
      • Fairly uncommon.
    3. Leptomeninges
      • Causes leptomeningitis, which may be:
        1. Suppurative
          • The most common form.
          • Neutrophils are the predominant cell type.
          • Caused by bacteria
            • E.g. E. coli and Streptococcus
          • There are often no gross lesions, but the brain may appear swollen and the meninges opaque.
          • Usually results in death.
        2. Eosinophilic meningoencephalitis
          • The classic example of this is porcine salt poisoning, when water has been restricted and the suddenly replenished.
          • Perivascular eosinophilic cuffing is seen in the cerebrum and meninges.
        3. Lymphocytic
          • Usually of viral origin.
        4. Granulomatous
          • Caused by fungal diseases and Mycobacteriosis.
    4. CNS parenchyma

Bacterial Infections

Pneumococcal meningitis. Image courtesy of BioMed Archive
  • Bacterial infections typically result in abscesses.
    • These may be single or multiple depending on the route of entry, and vary in size.
    • They contain a central, liquefied cavity.
  • There are differences between cerebral abscesses and those occuring elsewhere.
    • Encapsulation is slow.
      • This is due to a lack of fibroblasts.
      • There is therefore less collagen in the capsule.
    • Astrocytic glial fibers are not as strong as collagen
  • Other organisms may cause similar infections:
    • Rickettsial organisms
      • E.g. Ehrlichia
    • Spirochates
      • E.g. Leptospirosis

Viral Infections

  • Viral infections tend to reach the CNS by haematogenous spread and via peripheral nerves.
  • There are three hallmark lesions of CNS viral infections:
    1. Neuronal necrosis
    2. Gliosis
    3. Vascular changes
  • Several types of virus may cause inflammation in the CNS.
    Negri bodies, as seen in rabies. Image courtesy of BioMed Archive
    • Neurotropic, e.g.
      • Rabies (rhabdovirus)
      • Aujesky’s disease (herpesvirus)
      • Visna (ovine lentivirus)
    • Endotheliotropic, e.g.
      • Infectious canine hepatitis (canine adenovirus)
      • Classical swine fever (pestivirus)
      • Equine herpesvirus type 1 (herpes)
    • Pantropic
      • Infectious canine distemper (morbillivirus)
      • Infectious bovine rhinotracheitis (bovine herpesvirus type 1)
  • Other examples of viruses affecting the CNS:
    • Distemper
    • Parvovirus
    • Parainfluenza
    • Herpes
    • FIP
    • FIV
    • FeLV
    • Pseudorabies
    • Rabies

Prion Diseases

  • Prion diseases are also knowns as transmissible spongiform encephalopathies (TSEs).
  • They are a group of fatal neurodegenerative diseases which occur in a number of species, including man.
    • For example:
      • Bovine spongiform encephalopathy (BSE) in cattle
      • Scrapie in sheep
      • Chronic wasting disease in elk
      • Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and kuru in man
  • TSEs have a long incubation period, making them difficult to diagnose.

Aetiology

  • The aetiology of prion diseases is still highly controversial.
    • However, an abnormal isoform of the host-encoded prion protein (PrP) is seen in the brains of affected animals.
      • The normal host PrP changes its structure into the disease-associated form PrPSc.
    • The abnormal proteint (PrPSc) accumulates as amyloid fibrils in nervous tissue.
  • The agent appears to be highly resistant.

Pathology

Gross

  • Prion diseases cause NO GROSS LESIONS.

Hisological

  • TSEs typically cause what is known as the "microscopic triad":
    1. Spongiform change.
      • Vacuolation of neurons.
      • Particularly in nuclei.
    2. Astrogliosis
    3. Amyloid plaques
      • These are not always seen.

Non-Infectious Inflammatory Diseases

Granulomatous Meningoencephalitis (GME)

  • An idiopathic CNS conditon
  • May occur as:
    • A disseminated disease
    • A focal mass lesion
    • A primary occular disease
  • Brainstem signs are common, although the forebrain is primarily affected.
  • May be incorrectly diagnosed as lymphoma.
  • Changes are apparent in the CSF.
    • There is usually a mononucloear pleocytosis.
    • Sometimes only protein is elveated.
  • Diffuse inflammatory changes or a mass lesion will be seen by advanced imaging.
    • However, biopsy is required for a definative diagnosis.
  • Life span is between 6 months and 1 year from diagnosis.

Treatment

  • Immunosuppression:
    • Corticosteroids
    • Azathioprine
    • Cycophosphamide
  • Surgery
    • This is only appropriate if there is a focal mass.
  • Radiation therapy.

Pug Encephalitis

  • A CNS idiopathic condition
  • Affects pugs.
    • Similar conditions are seen in yorkshire and maltese terriers.
  • Officially known as necrotising meningoencephalitis of small dogs.
  • Characterised by histological forebrain inflammation and necrosis.
  • The disease is uniformly fatal.
    • Corticosterid treatment has no effect.

Clinical Signs of CNS Inflammation

  • Signs often reflect multiple levels of neurological involvement.
  • Generalised forebrain signs are seen.
  • Neck pain may be seen alone, or with other signs.

Diagnosis

  • History, physical and neurological examination.
  • Fundic examination may give clues as to whether a systemic infection is present.
  • CSF examination may help define the problem.

Treatment

  • Treatment is directed at a specific cause, if one can be found.
    • If a cause cannot be found, trimethoprim, clindamycin or doxycycline plus or minus corticosteroids may be used.