Difference between revisions of "CNS Inflammation - Pathology"

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#redirect[[:Category:Central Nervous System - Inflammatory Pathology]]
+
{{review}}
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 +
{{toplink
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|backcolour = E0EEEE
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|linkpage = Nervous System - Pathology
 +
|linktext =Nervous System
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|maplink = Nervous System (Content Map) - Pathology
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|pagetype =Pathology
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}}
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<br>
 +
==Introduction==
 +
 
 +
* Although the CNS is well protected, its defences against organisms that have already invaded are less well developed. This is due to:
 +
*# Minimal antibody production
 +
*# Cerebrospinal fluid providing a good culture medium for invading organisms.
 +
*# 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:
 +
**# '''Haematogenous entry'''
 +
**#* This is the most common route.
 +
**# '''Entry via the peripheral nerves'''
 +
**#* Organisms track within the axoplasm of axons.
 +
**#* For example, ''Listeria monocytogenes''.
 +
**# '''Penetrating trauma'''
 +
**#* For example, dehorning wounds, skull fracture or tail docking.
 +
**# '''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:
 +
*# '''Epidural space'''
 +
*#* Infection tends to manifest as abscess formation.
 +
*# '''Subdural space'''
 +
*#* Manifests as abscess formation.
 +
*#* Fairly uncommon.
 +
*# '''Leptomeninges'''
 +
*#* Causes leptomeningitis, which may be:
 +
*#*# 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.
 +
*#*# 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.
 +
*#*# Lymphocytic
 +
*#*#* Usually of viral origin.
 +
*#*# Granulomatous
 +
*#*#* Caused by fungal diseases and Mycobacteriosis.
 +
*# '''CNS parenchyma'''
 +
 
 +
==Bacterial Infections==
 +
[[Image:pneumococcalmeningitis.jpg|thumb|right|150px|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:
 +
*# Neuronal necrosis
 +
*# Gliosis
 +
*# Vascular changes
 +
* Several types of virus may cause inflammation in the CNS. [[Image:negribodies.jpg|thumb|right|150px|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 Disease]]==
 +
 
 +
==Non-Infectious Inflammatory Diseases==
 +
 
 +
===Granulomatous Meningoencephalitis (GME)===
 +
 
 +
* An [[CNS Idiopathic Conditions - Pathology|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 Conditions - Pathology|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 Disease - Pathology#Clinical Signs|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.

Revision as of 11:01, 1 July 2010


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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 Disease

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.