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CNS Inflammation - Pathology (view source)

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==Introduction==
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* Although the CNS is well protected, its defences against organisms that have already invaded are less well developed. This is due to:
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*# Minimal antibody production
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*# Cerebrospinal fluid providing a good culture medium for invading organisms.
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*# Inflammatory cell, antibody and drug entry to the CNS being impeded by the blood-brain barrier.
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===Classification of Inflammation===
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* CNS inflammation may manifest as encephalitis or meningitis.
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** These often co-exist.
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* The aetiology CNS inflammation may be:
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** Infectious
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*** Bacteria
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*** Fungi
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*** Protozoa
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*** Viruses or non-infectious.
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*** Infectious agents vary geographically.
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** Non-infectious
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*** No infectious cause can be found in 60% of meningitis cases.
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* Inflammation may also be broadly classified based on the nature of the exudate present.
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** '''Fibrinous'''
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*** Caused by bacteria infection (including ''Mycoplasma'').
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** '''Suppurative'''
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*** Caused by bacteria and fungi.
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** '''Granulomatous'''
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*** Caused by bacteria or fungi.
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** '''Lymphoplasmacytic'''
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*** Caused by viruses.
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** '''Haemorrhagic'''
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*** This is rare.
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*** Usually associated with septicemia or infarcts.
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==Routes of Entry==
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* CNS inflammation is usually the result of infection.
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** This may be caused by:
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*** Bacteria
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*** Fungi
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*** Protozoa
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*** Viruses
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* Organisms must first enter the CNS in order to establish infection.
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** There are several routes of entry that allow this:
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**# '''Haematogenous entry'''
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**#* This is the most common route.
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**# '''Entry via the peripheral nerves'''
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**#* Organisms track within the axoplasm of axons.
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**#* For example, ''Listeria monocytogenes''.
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**# '''Penetrating trauma'''
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**#* For example, dehorning wounds, skull fracture or tail docking.
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**# '''Direct spread of infection'''
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**#* From the nasal cavity, middle ear or paranasal sinuses.
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==Localisation of Infectious Organisms==
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* After entry, organisms may establish in one or more of four main areas:
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*# '''Epidural space'''
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*#* Infection tends to manifest as abscess formation.
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*# '''Subdural space'''
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*#* Manifests as abscess formation.
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*#* Fairly uncommon.
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*# '''Leptomeninges'''
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*#* Causes leptomeningitis, which may be:
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*#*# Suppurative
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*#*#* The most common form.
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*#*#* Neutrophils are the predominant cell type.
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*#*#* Caused by bacteria
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*#*#** E.g. ''E. coli'' and ''Streptococcus''
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*#*#* There are often no gross lesions, but the brain may appear swollen and the meninges opaque.
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*#*#* Usually results in death.
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*#*# Eosinophilic meningoencephalitis
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*#*#* The classic example of this is porcine salt poisoning, when water has been restricted and the suddenly replenished.
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*#*#* Perivascular eosinophilic cuffing is seen in the cerebrum and meninges.
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*#*# Lymphocytic
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*#*#* Usually of viral origin.
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*#*# Granulomatous
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*#*#* Caused by fungal diseases and Mycobacteriosis.
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*# '''CNS parenchyma'''
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==Bacterial Infections==
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[[Image:pneumococcalmeningitis.jpg|thumb|right|150px|Pneumococcal meningitis. Image courtesy of BioMed Archive]]
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* Bacterial infections typically result in abscesses.
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** These may be single or multiple depending on the route of entry, and vary in size.
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** They contain a central, liquefied cavity.
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* There are differences between cerebral abscesses and those occuring elsewhere.
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**  Encapsulation is slow.
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*** This is due to a lack of fibroblasts.
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*** There is therefore less collagen in the capsule.
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** Astrocytic glial fibers are not as strong as collagen
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* Other organisms may cause similar infections:
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** Rickettsial organisms
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*** E.g. ''Ehrlichia''
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** Spirochates
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*** E.g. Leptospirosis
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==Viral Infections==
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* Viral infections tend to reach the CNS by haematogenous spread and via peripheral nerves.
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* There are three hallmark lesions of CNS viral infections:
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*# Neuronal necrosis
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*# Gliosis
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*# Vascular changes
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* 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]]
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** '''Neurotropic''', e.g.
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*** Rabies (rhabdovirus)
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*** Aujesky’s disease (herpesvirus)
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*** Visna (ovine lentivirus)
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** '''Endotheliotropic''', e.g.
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*** Infectious canine hepatitis (canine adenovirus)
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*** Classical swine fever (pestivirus)
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*** Equine herpesvirus type 1 (herpes)
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** '''Pantropic'''
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*** Infectious canine distemper (morbillivirus)
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*** Infectious bovine rhinotracheitis (bovine herpesvirus type 1)
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* Other examples of viruses affecting the CNS:
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** Distemper
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** Parvovirus
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** Parainfluenza
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** Herpes
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** FIP
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** FIV
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** FeLV
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** Pseudorabies
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** Rabies
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==Prion Diseases==
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* Prion diseases are also knowns as transmissible spongiform encephalopathies (TSEs).
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* They are a group of fatal neurodegenerative diseases which occur in a number of species, including man.
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** For example:
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*** BSE in cattle
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*** Scrapie in sheep
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*** Chronic wasting disease in elk
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*** CJD, Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and kuru in man
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* TSEs have a long incubation period, making them difficult to diagnose.
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===Aetiology===
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* The aetiology of prion diseases is still highly controversial.
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** However, an abnormal isoform of the host-encoded prion protein (PrP) is seen in the brains of affected animals.
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*** The normal host PrP changes its structure into the disease-associated form PrPSc.
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** The abnormal proteint (PrPSc) accumulates as amyloid fibrils in nervous tissue.
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* The agent appears to be highly resistant.
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===Pathology===
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====Gross====
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* Prion diseases cause NO GROSS LESIONS.
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====Hisological====
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* TSEs typically cause what is known as the "microscopic triad":
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*# Spongiform change.
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*#* Vacuolation of neurons.
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*#* Particularly in nuclei.
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*# Astrogliosis
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*# Amyloid plaques
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*#* These are not always seen.
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==Non-Infectious Inflammatory Diseases==
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===Granulomatous Meningoencephalitis (GME)===
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* An [[CNS Idiopathic Conditions - Pathology|idiopathic CNS conditon]]
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* May occur as:
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** A disseminated disease
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** A focal mass lesion
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** A primary occular disease
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* Brainstem signs are common, although the forebrain is primarily affected.
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* May be incorrectly diagnosed as lymphoma.
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* Changes are apparent in the CSF.
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** There is usually a mononucloear pleocytosis.
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** Sometimes only protein is elveated.
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* Diffuse inflammatory changes or a mass lesion will be seen by advanced imaging.
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** However, biopsy is required for a definative diagnosis.
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* Life span is between 6 months and 1 year from diagnosis.
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====Treatment====
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* Immunosuppression:
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** Corticosteroids
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** Azathioprine
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** Cycophosphamide
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* Surgery
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** This is only appropriate if there is a focal mass.
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* Radiation therapy.
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===Pug Encephalitis===
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* A [[CNS Idiopathic Conditions - Pathology|CNS idiopathic condition]]
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* Affects pugs.
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** Similar conditions are seen in yorkshire and maltese terriers.
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* Officially known as necrotising meningoencephalitis of small dogs.
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* Characterised by histological forebrain inflammation and necrosis.
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* The disease is uniformly fatal.
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** Corticosterid treatment has no effect.
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==Clinical Signs of CNS Inflammation==
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* Signs often reflect multiple levels of neurological involvement.
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* Generalised [[Forebrain Disease - Pathology#Clinical Signs|forebrain signs]] are seen.
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* Neck pain may be seen alone, or with other signs.
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==Diagnosis==
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* History, physical and neurological examination.
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* Fundic examination may give clues as to whether a systemic infection is present.
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* CSF examination may help define the problem.
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==Treatment==
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* Treatment is directed at a specific cause, if one can be found.
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** If a cause cannot be found, trimethoprim, clindamycin or doxycycline plus or minus corticosteroids may be used.
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