CNS Inflammation - Pathology

Central Nervous System Inflammation Overview

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.

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.

Central Nervous System Infectious Inflammation

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

Category:CNS 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.

Necrotising Meningoencephalitis

Category:CNS Non-Infectious Inflammatory Diseases

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.

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