Meningoencephalomyelitis Flashcards
Define EME
eosinophilic meningoencephalitis (EME) is a disorder of unknown etiology that is characterised by infiltration of eosinophilis. It can be a component of fungal/protozoal/parasitic mening, but can be idiopathic as well.
typical CSF findings in EME
eosinophilic pleocytosis (>20%)
Pathophysiology of EME
an autoimmune etiology is suspected. A type I and/or type IV hypersensitivity reaction may be involved with eosinophils releasing neurotoxic substances
Common MRI findings with idiopathic eosinophilic mening in dogs
- focal or multifocal intra-axial lesions are observed primarily within cortical grey matter and meninges +/- white matter lesions
- contrast enhanced meninges ( cortical atrophy or necrosis)
- cerebral sulci enlargement
- lesions are typically hyperintense on T2-weight images; hypo- to hyperintense on fluid-attenuated inversion recovery (FLAIR) images; hypo- to isointense on T1-weighted images; and may or may not contrast enhance
- can also be normal
list potential infectious etiologies of EME in dogs
- canine distemper virus
- rabies
- neosporosis
- toxoplasmosis
- cryptococcosis
- protothecosis
- neural angiostrongylosis
- intracranial cuterebriasis
- dirofilarial larval migration
- bacterial infection
typical signalment for eme
- large-breed dogs; goldens and rottweilers
- 4 months to 10 years
- males predisposed
MOA of corticosteroids in EME
- immunosuppressive therapy; glucocorticoids enter the cell nucleus to interfere with transcription of products important to immune and inflammatory processes
- neuroprotective effects
Prognosis of dogs with idiopathic EME
- good with treatment; 75% respond well to therapy
- relapses possible
what is pug dog encephalitis?
necrotizing encephalitis
What distinguishes NME and NLE?
lesion distribution;
- NME primarily affects cerebral gray matter
- NLE within subcortical + brainstem white matter
what is NE?
necrotizing encephalitis; an aseptic inflammatory, necrotizing disease of the brain. Only reported in dogs.
- two discrete forms (1) necrotising meningoencephalitis (NME) + (2) necrotizing leukoencephalitis (NLE)
etiology of Necrotizing meningitis
- thought to be an autoimmune disease targeting cellular components that are normally shielded
- no infectious organisms isolated
- pathogenesis likely multifactorial with genetic predisposition and aberrant immune system stimulation
why is NME also known as pug dog mening?
- strong familial inheritance of NME has been documented in the pug; associated with risk loci on chromosome 15 and the dog leukocyte antigen (DLA) II region of chromosome 12
Pathophysiology of NME
- thought to be a T-cell mediated autoimmune disease
- altered display of self-antigens to the immune system –> presentation of CNS self antigen to T-cells or cross-reaction of antibodies against a self-protein antigen.
- activated T-cells cause a cascade of changes; loss of blood-brain barrier integrity, cytokine activation and other inflammatory changes leading to oxidative stress, neurotoxicity, apoptosis, astrogliosis, microglial activation
typical CSF findings in NME
- mononuclear or lymphocytic pleocytosis (most commonly)
+/- increased protein concentration (disruption of blood/brain barrier) or intrathecal IgG production
is genetic testing available for NME?
- testing for the DLA gene markers on chromosome 12 is commercially available in the USA and UK
- homozygous affected dogs have an observed risk of 12.75 for NME compared to normal or heterozygous (0-1.08)
typical NME signalment
- young adult, small breed dogs
- pug (fawn, females), yorkshire terrier, maltese, chis, pekingese, papillon, shih tzu, coton de tulear, brussels griffon –> NME
- french bulldog + yorkshire terrier –> NLE
common NLE CS
central blindness, seizures, central vestibular signs
common NME CS
- forebrain signs; seizures, central blindness, circling, head pressing, altered mentation, head +/- cervical pain
MOA of cyclosporine in NME
- kinase/phosphorylase inhibitors
- calcineurin inhibition stops translocation of nuclear factor of activated T-cells (NFAT) into the nucleus = inhibition of IL-2 + proinflammatory cytokines transcription
- only modified formulations of cyclosporine (Atopica, Neoral) are well absorbed (administer 1-2hrs before a meal)
MOA of DNA Alkylators
- alter DNA conformation by insertion of alkyl group which interferes with DNA repair and replication, as well as inhibiting transcription. They are cell cycle nonspecific.
- Procarbazine, Lomustine, Cyclophosphamide penetrate into the CNS well
examples of antimetabolites
- those affecting purine synthesis; mycophenolate and azathioprine
- those affect pyrimidine synthesis; cytosine arabinoside, leflunomide
MOA of azathioprine
interferes with pathways for synthesis of purines; greatest effect on humoral immunity. Requires 8-12 weeks to achieve maximal immunosuppressive effects.
MOA of leflunomide
- interferes with the pathways for synthesis of pyrimidines
- metabolized into its active form by intestinal mucosa – works by inhibiting dihydroorotate dehydrogenase thereby blocking T and B cell proliferation
- also has limited antiviral activity
NME prognosis
- fatal without treatment
- approx. 44-75% dogs respond to therapy; 26% die within 7 days of diagnosis
- reported survival times; 1-1096 days
negative prognostic indicators of NME
- presence of seizures, decreased mentation, mass effect
- higher CSF total nucleated cell count, increased neutrophil conc, abnormal CSF at 3 months post diagnosis
What is the scientific name of rat lung worm?
Angiostrongylus cantonensis
What is the life-cycle and transmission of A.cantonensis?
L1 passed in rat faeces –> ingested by slugs/snails and mature to L3 –> rats/other hosts ie. dogs ingest the slug –> L3 migrate from GIT to brain (develop into subadult) then migrate to pulmonary arteries –> mature and mate –> eggs hatch in lungs –> migrate to trachea and are coughed up and swallowed –> L1 pass in faeces
CSF tests for A.cantonensis
- Anti-A.cantonensis IgG in the CSF can be detected via enzyme-linked immunosorbent assay (ELISA)
- PCR reaction
- loop-mediated isothermal amplification (LAMP) assays
pathophysiology of A.cantonensis meninge
- L3 leave GIT via lymphatics and veins. L3 exhibit neurotropism and travel via peripheral nerves and nerve roots to CNS.
- Damage to CNS tissue occurs from mechanical damage from larval migration and haemorrhage
- severe eosinophilic meningoencephalitis occurs in response to larval antigens
Treatment of A.cantonensis
high dose glucocorticoids for a minimum of 6-8 weeks - anthelmintics can worsen CS and result in death
