Degenerative encephalopathies Flashcards
Which 2 lysosomal storage diseases are LATE onset?
1) fucosidosis
2) NCL
Which 2 lysosomal storage disease are affecting both CNS+PNS?
1) Globoid cell leukodystrophy (myelin)
2) Fucosidosis (myelin)
also can be:
Glycogenoses –> myopathy
Sphingomyelinoses–> myopathy
State 3 lysosomal diseases in which you can have skeletal abnormalities?
1) mannosidosis
2) mucopolysacharidosis
3) mucolipidosis II
Which 5 lysosomal storage diseases can have ocular abnormalities and which?
Corneal lesions
gangliosidosis - cat
mannosidosis - cat
MPS VII - dogs
Retinal degenration
NCL - dogs
mucolipidosis II -cats
Which genetic mutation has been associated with Globoid Cell Leukodystrophy in dogs?
A) ARSB Gene
B) GALC Gene
C) IDUX Gene
D) PPT1 Gene
B) GALC Gene
Galactocerebrosidade
Dogs - crossbreeds
MPS I - Goldens - IDUX
MPS VI - Great Dnae etc. ARSB
NCL -Cane corso - dogs - PPT1
State breeds of dogs with Globoid Cell Leukodystrophy
WHWT (famous)
Australian Kelpies (famous)
Cairn Terriers
Irish setter
Crossbreed
Which is the hallmark of histopathology in Globoid Cell leukodystrophy. Any specific stains?
Globoid cells = macrophages, swollen, ‘globoid’ in WM, perivascular spaces infiltrates
Demyelination in both CNS and PNS
PAS - positive endocytoplasmatic material
Which 2 features are characteristic in MRI of Globoid cell leukodystrophy?
1) WM T2/T1 hyperintensity (diffuse demyelination) + CE
2) T1 HYPER of corpus callosum
State 2 dog and 2 cat breeds for NCL and associated genetic muations.
Dogs:
Cane Corso
Daxy
Cats:
DSH
Siamese
Dogs –PPT1 gene (NCL type 1 or CLN 1)
Cats - MFSD8 gene (NCL type 7 or CCLN 7)
What is the hallmark (1 lesion) of MRI of NCL?
Brain atrophy
What is the hallmark of NCL in histopathology of brain?
Distended alive neurons or glial cells in CNS full of pale yellow to eosinophilic intracytoplasmatic inclusions (lipofuscin)
In which breeds of dogs and cats gangliosidosis has been reported?
Shiba Inu - dog
Japanese domestic cat - cat
Which genetic mutations are associated with GM1 and GM2 in dogs and cats?
A) HEXB gene (GM2), GLB1 gene (GM1)
B) HEXB gene (GM2), GALC gene (GM1)
C) MANBA gene (GM2), GLB1 gene (GM1)
D) GALC gene (GM2), GARC gene (GM1)
A.
HEXB gene - Shiba Inu and Japanese domestic cat with GM2
GLB2 gene - Shiba Inu with GM1
What is the hallmark of MRI in galgiosidosis? What can be seen in later stages?
Corpus callosum and rostral commisure abscence/hypoplasia
Later stages: Bilateral symmetric T2 hyper/T1 hypointense lesions in CAUDATE NUCLEI
Which breed has been reported with fucosidosis?
English Sprinber Spaniel
Which clinical finding is a feature of fucosidosis in dogs?
Palpable ulnar nerve - infiltration of nerves by lipid-filled phagocytosed Schann cells
Which is the genetic mutation associated with β-mannosidosis?
A) MANBB gene
B) MANBA gene
C) MANBC gene
D) MANN gene
B) MANBA gene
State 2 dog breeds and 1 cat breed with mannosidosis.
Dogs:
GSD
Crossbreed
Cats: DSH, DLH, Persian
State 2 breeds of dogs and 1 cat breed with L2HGA aciduria.
Dogs:
Staffies (famous)
Yorkies
WHWT
Crossbreed
Cat: DSH
Which is the genetic mutation responsible for L2HGA aciduria in dogs?
L2HGDH gene
What is unique for the MRI of L2HGA aciduria in contrast to other degneerative encephalopathies in dogs?
Which unique feature has been seen in a single feline MRI?
Most of degenerative encephalopathies have cortical atrophy, but L2HGA has the opossite:
INCREASED FOREBRAIN AND CEREBELLAR VOLUME due to thickened cortical GM
This GM is T2 and FLAIR hyperintense , bilateral symmetrical affecting cortex, basal nuclei, thalamus, cerebellar, brainstem nuclei, etc.
Single felijne MRI: - rounded intrax-axial T2hyper,T1 hypo, non CE multicystic lesions within the subcortical WM containing CSF
What is the storage problem in Lafora disease and which is the genetic mutation? Which protein does this gene encodes?
-Polyglucosan storage disease –> abnormal metabolism of glucogen –> intracytoplasmic substate accumulation (not in lysosomes)
NHLRC1 or EPM2B gene –> E3 ubiquitin protein ligase-1
State 2 breeds predisposed to Lafora disease.
Wire haired daxies (famou)
Beagle (famous)
Chihuahua
French Bulldogs
Crossbreed etc.
What is the percentage of Wire Haired Daxies that are carriers of the abnormal gene for Lafora (EPM2B gene)?
A) 5%
B) 20%
C) 40%
D) 70%
B - 20%
Which is the median age of onset of Lafora disease?
7-8 yo
State 4 main clinical signs of Lafora disease
1) Myoclonic seizures photosensitive or spontaneous (80%)
2) hypnic myoclonus 50%
3) GTC seizures 40%
4) focal seizures, (less common)
5) later onset cognitive dysfunctin 50%, deafness, aggression, blindness, faecal/urinary incontinecne due to dementia
Which is the hallmark of Lafora disease in histopathology? Which stains to use?
Lafora bodies (=abnormal glucogen into polyglucosan bodies that are basophilic rounded) in GM (prominent in cerebellar cortex) but also other brain cells or myocytes
Highest yield to find lafora bodies close to myotendinous junction and myofascial union segments.
Stains: HE, PAS, Alcian blue
State 2 IHC stains for lafora bodies.
Laforin
Calbindin
MRI findings in Lafora disease:
A) Cereberocortical atrophy
B) Cerebellar hypoplasia
C) 50% Normal - 50% abnormal (brain atrophy)
D) 100% Normal
C
