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− | {{review}}
| + | #redirect[[:Category:Central Nervous System - Inflammatory Pathology]] |
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− | {{toplink
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− | |backcolour = E0EEEE
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− | |linkpage = Nervous System - Pathology
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− | |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>
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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]] | |
− | * 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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