Difference between revisions of "CNS Inflammation - Pathology"

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#redirect[[:Category:Central Nervous System - Inflammatory Pathology]]
 
 
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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 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:
 
*** BSE in cattle
 
*** Scrapie in sheep
 
*** Chronic wasting disease in elk
 
*** 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":
 
*# Spongiform change.
 
*#* Vacuolation of neurons.
 
*#* Particularly in nuclei.
 
*# Astrogliosis
 
*# Amyloid plaques
 
*#* These are not always seen.
 
 
 
==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.
 

Latest revision as of 12:55, 8 March 2011