BRAIN - inflammatory Flashcards
(52 cards)
In MUO, focal signs are associated with an increased survival compared to dogs with multifocal signs: true or false?
False
(a study from 1998 found this association, but 3 more recent studies didn’t found this result)
Cornelis, 2019
Give molecules with following action:
- Regulation of gene expression
- DNA Alkylation (antiproliferatives)
- Antimetabolites: purine & pyrimidine
- Kinase and Phosphorylase Inhibitors
- Inhibition of microtubule formation
Regulation of Gene Expression
Enter nucleus to interfere directly with transcription of gene products.
Glucocorticoids, vitamin D analogues
DNA Alkylation (antiproliferatives)
Interfere directly with the structure of DNA in order to block subsequent replication, which is required for cell proliferation.
Cyclophosphamide, lomustine, procarbazine, chlorambucile
Antimetabolites
Interfere with pathways responsible for the synthesis of the purine (adenine, guanine) or pyrimidine (thymine, cytosine) molecules necessary for DNA synthesis and cell proliferation, or with enzymes involved in other processes critical to cell survival or proliferation.
Inhibits purine synthesis: 6-mercaptopurine, azathioprine, mycophenolate mofetil
Inhibits pyrimidine synthesis: Cytosine arabinoside, leflunomide
Kinase and Phosphorylase Inhibitors
The most common enzyme inhibited is calcineurin, which belongs to the serine/threonine phosphatase superfamily and acts to dephosphorylate nuclear factor of activated T cells (NFAT). This interferes with the translocation of NFAT into the nucleus of activated T cells, impairing a number of important functions, such as the production of IL-2 and other proinflammatory cytokines.
Cyclosporine A
Inhibition of microtubule formation in mitotic spindle
Arrest of dividing cells at the metaphase stage
Vincristine
Which autoantibodies can be found in Pugs with MUO?
GFAP in CSF
Which factors are associated with the short-term prognosis in MUO?
1. Decreased mentation at presentation
2. Presence of seizures
3. Increased percentage of neutrophils on CSF analysis
4. Bodyweight
5. Duration of clinical signs and treatment prior to diagnosis
1,2,3
Gene associated with risk for NME
dog leucocyte antigen MHC class II (chromosome 12)
polymorphism in chromosome 15 Pug, 4 Maltese
how many Pug carry at-risk gene for NME
2/3 of pug carry at least 1 DLA at-risk haplotype, 6-18% carry the high risk homozygous DLA haplotype
most common sign of early NME/clinical NME
early NME: multifocal spinal hyperesthesia, paw placement deficit, reduced menace response (90%), mild lethargy (75%), proprioceptive ataxia (65%)
clinical NME: seizure, circling, visual deficits, behavior change , lethargy
MRI/csf change in early/clinical NME
MRI change in 90% of ealry form: meningeal enhancement, focal contrast-enhancing lesion within parenchyma, T2 hyperintense lesion (early necrosis)
abnormal CSF in 50%
clinical: loss W/G matter distinction, parenchymal inflam/necrotic lesion, leptomeningeal enhancement. Maj in parietal/occipital lobe
abnormal CSF 90-80% (lymphocytic pleocytosis)
frequency + risk factors for postencephalitic epilepsy development?
% developing resistant epilesy
23% develop PEE
1/ Acute symptomatic seizures = seizures at the early stage of the disease
2/ MRI lesions in the hippocampus
They were younger when compared with those without PEE and had shorter MST.
Among PEE, 21% develop drug-resistant epilepsy
,
What are the risk factors for dying with MUO?
During first week:
Decreased mentation
Seizures
Increased neutrophils in CSF
After: obtundation
Note: large breed dogs present more commonly decreased mentation than small and medium breed dogs, but no overall difference in MST
Dogs with NE are usually older than dogs with GME: true or false?
False
NE: <4 yo
GME: 4-8 yo
What is the clinical sign that is most common in large breed dogs than small breed dogs with MUO?
Decreased mentation
What are the 3 genetic risk factors identified for NME in dogs?
∼75% of Pugs with NME have a specific combination of alleles coding for major histocompatibility complex class II (MHC II) molecules on chromosome 12 containing exons for the dog leukocyte antigen and conferring on them a relative risk of 5.45 of developing the disease
In Maltese dogs, ILR7 on chromosome 4
FBXW7 on chromosome 15 in Pugs + Maltese
6-18% Pugs carry high risk homozyg haplotype
In MUO, seizures or altered mentation are associated with significantly shorter ST: true or false?
True
They have also a significantly higher risk of dying within the first week after diagnosis.
What are the most common location of lesions of NME in MRI?
The most common MRI abnormalities reported in dogs with NME are asymmetrical, multifocal and located in the forebrain (more severe lesions in parietal and occipital lobes); are hyperintense on T2W and FLAIR images; and typically affect the cortical grey and subcortical white matter with loss of grey/white matter demarcation and variable degrees of contrast enhancement of the parenchymal lesions on T1W postcontrast images,
However, cerebellar and brainstem lesions were also detected in 4/18 and 3/18 cases in one study, respectively,
Meningeal enhancement can also be present, accompanied by mass effect and varying degrees of ventriculomegaly
A younger age at time of diagnosis with MUO is associated with improved survival: true or false?
true
In MUO, oligoclonal bands in CSF are indicative of B cell response? T cell response?
Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together.
MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response.
What is the most common presentation of LGI1 positive autoimmune encephalitis in cat?
Similar to human cases, most cats with LGI1-antibodies had a history of focal seizures (83%), clustering in the majority (88%), with interictal behavioural changes (73%).
1/ Pug dog encephalitis is described as a seasonal disease with a CSF neutrophilic pleocytosis
2/ Affected dogs are predominantly male dogs less than one year old and the lesions are widely distributed in the brain as it is observed in the chihuahua
3/ Affected dogs are predominantly young adult female dogs and the lesions are most commonly seen in the prosencephalon although up to 40% of the dog have cerebellum lesions
4/ Pug dog encephalitis is strongly suspected to be more likely to occur following rabies vaccination
3
What of the following statements is incorrect?
- Dogs with optic neuritis as part of a multifocal MUO respond significantly less well to treatment than dogs with isolated optic neuritis.
- Median CSF TNCC in dogs with isolated optic neuritis is 5 cells and median TP 35, with over 50% of the dogs having normal CSF analysis
- Males were slightly more represented in the group of isolated optic neuritis, contrary to what is the case for the MUO group
- Overall, between 65 and 73% of cases remained blind despite treatment.
1
What of the following statements is incorrect?
- The environment of dogs, urban vs rural has not been proven to be a risk factor for development of MUO
- The presence of Prevotellaceae in the digestive tract of dogs has been positively correlated with development of MUO
- A haplotype in the CFA 12 containing the regions for canine leukocyte antigen class II has been identified as a risk factor for NME in Pugs.
- Pugs with MRI having a heavier lesion burden in MRI have longer time from disease onset to MRI
2
Which factors were associated with complete recovery in optic neuritis (isolated or with MUO)?
Reactive PLR
Absence of fundoscopic lesion
Younger age
Lower CSF TNCC
The 2 last were more significantly associated with I-ON compared to MUO group.
What type of serological abnormality can be detected in cats with suspected limbic encephalitis?”
High levels of voltage-gated potassium channel complex antibodies
What is the risk of previous corticosteroid therapy in case of discospondylitis?
Prior steroid therapy was associated with an increased risk of progressive neurological dysfunction
