Brain - inflammatory

Question 1

In MUO, focal signs are associated with an increased survival compared to dogs with multifocal signs: true or false?​

Answer 1

False​

(a study from 1998 found this association, but 3 more recent studies didn’t found this result)​

Cornelis, 2019​

Question 2

Give molecules with following action:​
- Regulation of gene expression​
- DNA Alkylation (antiproliferatives)​
- Antimetabolites: purine & pyrimidine​
- Kinase and Phosphorylase Inhibitors​
- Inhibition of microtubule formation​

Answer 2

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​

Question 3

Which autoantibodies can be found in Pugs with MUO?​

Answer 3

GFAP in CSF​

Question 4

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

Answer 4

1,2,3

Question 5

Which one is a risk factor for the development of postencephalitic epilepsy in dogs with MUO?​

1. MRI abnormalities in the hippocampus​
2. Lesions in occipital lobes​
3. Hydrocephaly​
4. Young age

Answer 5

1

Question 6

What are the 2 risk factors for post encephalitis epilepsy development?​

Answer 6

23% develop PEE​

Acute symptomatic seizures = seizures at the early stage of the disease​
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​

Question 7

What are the risk factors for dying with MUO?​

Answer 7

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​

Question 8

Gene associated with risk for NME

Answer 8

dog leucocyte antigen MHC class II (chromosome 12)
polymorphism in chromosome 15 Pug, 4 Maltese

Question 9

how many Pug carry at-risk gene for NME

Answer 9

2/3 of pug carry at least 1 DLA at-risk haplotype, 6-18% carry the high risk homozygous DLA haplotype

Question 10

most common sign of early NME/clinical NME

Answer 10

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

Question 11

MRI change in early/clinical NME

Answer 11

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)

Question 12

frequency + risk factors for postencephalitic epilepsy development?
% developing resistant epilesy

Answer 12

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

Question 13

What are the risk factors for dying with MUO?

Answer 13

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

Question 14

Dogs with NE are usually older than dogs with GME: true or false?

Answer 14

False

NE: <4 yo
GME: 4-8 yo

Question 15

What is the clinical sign that is most common in large breed dogs than small breed dogs with MUO?

Answer 15

Decreased mentation

Question 16

What are the 3 genetic risk factors identified for NME in dogs?

Answer 16

∼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 and FBXW7 on chromosome 15, both involved in the immune system regulation, could be implicated in necrotizing encephalitis

Question 17

In MUO, seizures or altered mentation are associated with significantly shorter ST: true or false?

Answer 17

True

They have also a significantly higher risk of dying within the first week after diagnosis.

Question 18

What are the most common location of lesions of NME in MRI?

Answer 18

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

Question 19

A younger age at time of diagnosis with MUO is associated with improved survival: true or false?

Answer 19

true

Question 20

In MUO, oligoclonal bands in CSF are indicative of B cell response? T cell response?

Answer 20

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.

Question 21

What is the most common presentation of LGI1 positive autoimmune encephalitis in cat?

Answer 21

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%).

Question 22

What are the most common location of lesions of NLE in MRI?

Answer 22

Multiple asymmetrical cerebral white matter and brainstem abnormalities have been detected. These abnormalities were typically hyperintense on T2W and FLAIR images and often included multiple cystic areas of necrosis.
Contrast enhancement of parenchymal abnormalities was minimal in two reported studies. There was lack of meningeal enhancement and mass effect, with varying degrees of ventriculomegaly in a third study.

Question 23

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

Answer 23

3