Congenital Malformations and Inherited Diseases of the Nervous System Flashcards
(68 cards)
1
Q
T/F: congenital malformations of the NS are common
A
true: high degree of specialization and complexity
2
Q
causes of congenital malformations of the NS
A
- genetic errors: spontaneous or inherited mutations or chromosomal abnormalities
- environmental factors (teratogens): most act at specific times during gestation and affect only certain cell types
3
Q
what are the 4 types of teratogens?
A
- physical agents
- nutritional factors
- toxins
- viruses
4
Q
what are examples of physical agents
A
trauma, radiation
5
Q
what are examples of nutritional factors?
A
- hypovitaminosis A: optic nerve hypoplasia
- congenital copper deficiency of lambs: swayback: white matter necrosis/cavitation
6
Q
what are examples of toxins?
A
ex: steroidal alkaloid from Veratrum californicum (skunk cabbage) in sheep at day 14 gestation
= synopthalia (failure of 2 eye globes to separate) and holoprosencephaly
7
Q
what viruses cause malformations of NS?
A
- feline panleukopenia virus = cerebellar hypoplasia
- bovine diarrheal virus = cerebellar hypoplasia, hydranencephaly, porencephaly
8
Q
what does veratrum californicum cause?
A
sheep cabbage; causes synophthalia in lambs (failure of 2 eye globes to separate) and holoprosencephaly
9
Q
what is synophthalmia? what causes it?
A
failure of 2 eye globes to separate, caused by Veratrum californicum (skunk cabbage) at day 14 of gestation
10
Q
how do you diagnose congenital malformations of the CNS?
A
- immature animal with neuro signs occurring immediately after birth or within first weeks of life
- signs usually non progressive
- signs may progress rapidly
- some conditions may have signs occur later in life
- some malformations are obvious externally while others require sectioning of brain/spinal cord
11
Q
cranium bifidum (cranioschisis)
A
- midline bony defect in the cranium: neural tube closure defect
- commonly see things protrude thru the defect: ex: meningocele in the horse (sac like protrusion of meninges thru defect)
- or meningocephalocele (sac-like protrusion of meninges and brain parenchyma thru defect)
12
Q
in what defect can you see meningocele and meningocephalocele?
A
cranium bifidum (cranioschisis): midline bony defect in the cranium. neural tube closure defect
13
Q
you see a colt on necropsy that has a large protrusion from its head. you diagnose it as a meningocephalocele. what congenital issue do you suspect has occurred?
A
this colt has cranium bifidum: neural tube closure defect.
14
Q
spina bifida
A
- neural tube closure defect: midline bony defect in vertebral column
- usually lumbar, sacral or caudal vertebrae
- ranges from failure of closure to vertebral arches (most common) to agenesis of vertebrae
- may be accompanied by meningocele or meningomyelocele or myelodysplasia (abnormal formation of spinal cord)
- reported in most species
15
Q
what can accompany spina bifida?
A
- may be accompanied by meningocele or meningomyelocele or myelodysplasia (abnormal formation of spinal cord)
- reported in most species
16
Q
what are neuronal migration disorders?
A
- genetic defects resulting in interference with normal migration of neurons during development
- classic: lissencephaly (agyria): cerebrum has smooth surface without gyri and sulci
17
Q
you see a rat on necropsy whose brain has no gyri or sulci present. what are your thoughts?
A
normal in rats/rodents, but in a lot of others species causes abnormalities.
18
Q
you see a calf on necropsy that has cylopia. what do you suspect is the cause?
A
veratrum californicum: skunk cabbage ingestion at 14 days gestation
19
Q
what are encephaloclastic defects?
A
formation of fluid-filled cavities in brain resulting from destruction of immature neuroblasts preventing appropriate migration and development
20
Q
when do encephaloclastic defects occur?
A
usually in utero
21
Q
what are the 2 encephaloclastic defects?
A
- porencephaly: smaller cavities/holes in cerebral hemispheres. less severe
- hydranencephaly: more severe destructive event resulting in massive cerebrocortical necrosis (grey and/or white matter) with almost complete loss of pre-existing tissue. compensatory expansion of the lateral ventricles. super severe
22
Q
what is worse, porencephaly or hydranencephaly?
A
hydranencephaly
23
Q
you see a lamb on necropsy that has small cavities all throughout the cerebral hemispheres. what kind of defect is this and what has caused it?
A
porencephaly: encephaloclastic defect, possible cause is border disease virus
24
Q
what are common eitiologies of encephaloclastic defects?
A
in utero viral infections: BVDV, bluetongue, border disease virus. difficult to differentiate from hydroencephalus.
- vascular injury/vasculitis (humans)
25
what viruses commonly cause encephaloclastic defects?
BDVD, bluetongue virus, border disease virus, CSF
26
several lambs from a flock of sheep in germany were aborted or still born with several neuromuscular congenital malformations.
image 1: small defect/cavity in brain/porencephaly.
image 2: severe arthrogryposis/malformation and torticolis (neck bent to side)
what are some potential causes of these?
BDVD, bluetongue, akabane virus, cache valley virus are differentials
germany is a hint bc it is foreign animal: Schmallenberg virus (not important)
27
what is the most common malformation in the CNS?
hydrocephalus
28
what is hydrocephalus?
excessive accumulation of cerebrospinal fluid = expansion of ventricular system +/- subarachnoid spaces
29
what are the types of hydrocephalus?
1. non-communicating (most common)
2. communicating (rare)
3. hydrocephalus ex vacuo
30
what is non-communicating hydrocephalus?
- fluid within ventricular system
- obstruction anterior to lateral apertures of the 4th ventricle
- seen at the mesencephalic aqueduct!
31
where is non-communicating hydrocephalus most commonly seen?
mesencephalic aqueduct
32
what is communicating hydrocephalus?
rare, excess fluid in ventricular system and subarachnoid spaces
- malformation of arachnoid villi
33
what is hydrocephalus ex vacuo?
loss of brain tissue (ex hydranencephaly) = dilation of ventricular system
34
what are signs of hydrocephalus on necropsy?
- dilation of ventricles: secondary compression atrophy of white mattera
- may have flattened gyri and shallow sulci
- possible herniation thru foramen magnum (depending on how rapid obstruction occurs)
so much swelling of brain. depending on how quick it is, can see so much swelling that there is no compensation = herniation (not often seen congenitally)
35
what are the 2 causes of hydrocephalus?
1. congenital
2. acquired
36
congenital hydrocephalus
- most common in toy and brachycephalic breeds of dogs and calves
- associated with enlargement of cranium (doming) and open fontanelles
- most commonly a malformation of mesencephalic aqueduct!!
37
acquired hydrocephalus
- obstruction of CSF flow due to inflammation (ex FIP), neoplasia (glioma, choiroid plexus tumor, appendymoma, etc
- location varies
38
what is the appropriate term for a dilation of the ventricular system secondary to an encephaloclastic defect such as hydranencephaly?
hydropcephalus ex vacuo
39
what location of stenosis is most commonly found in congenital hydrocephalus?
mesencephalic aqueduct
40
malformation of the spinal cord
hydromyelia, syringomyelia
41
what is hydromyelia?
- abnormal dilation of central canal of spinal cord
- most are congenital (genetic or infectious)
- acquired are rare (similar causes to acquired hydrocephalus)
42
abnormal dilation of central canal of spinal cord
hydromyelia
43
syringomyelia
- cystic fluid-filled tubular cavity (syrinx) within the spinal cord that is NOT LINED BY EPENDYMA
- congenital or acquired (rupture of ependyma with secondary cavitation)
- dogs and calves: weimaraner and CKCS (chiari like malformation)
44
what are the classic dog breeds to get syringomyelia?
weimaraners and CKCS
45
you see a king charles spaniel on necropsy and see dilations in the spinal cord. they are cystic and fluid-filled. what is your diagnosis?
syringomyelia
46
malformation of the cerebellum
cerebellar hypoplasia: one of the most common congenital malformations of the CNS
47
cerebellar hypoplasia
- one of the most common congenital malformations of CNS
- gross: cerebellum is decreased in size
- microscopically: decreased numbers of purkinje cells and granular layer cells: destruction of mitotically active external granular cells
48
what cells are lost microscopically with cerebellar hypoplasia?
purkinje cells and granular layer cells: destruction of mitotically active external granular cells (ex parvovirus)
49
what are the viral causes of cerebellar hypoplasia?
1. parvovirus: feline panleukopenia, canine parvovirus
2. pestiviruses: BVDV (fetal infx at 100-150 days gest), classical swine fever, border disease virus
50
common causes of cerebellar hypoplasia
1. VIRUSES!!
2. inherited genetic defect
3. toxins: ex piglets from sows treated with organophosphate insecticide during second half of gestation
51
what do you need to differentiate cerebellar hypoplasia from?
cerebellar cortical abiotrophy (CCA)
52
what is cerebella cortical abiotrophy (CCA)
abiotrophy: lack of a vital, nutritive substance necessary for normal cell lifespan
- premature degeneration/necrosis and loss of Purkinje cells and granular layer cells (cerebellum can be normal or smaller size)
- intrinsic metabolic defect suspected (mostly autosomal recessive)
- early onset and progressive (but not at birth!!!)
53
how can you differentiate cerebellar hypoplasia from cerebellar cortical abiotrophy?
cerebellar hypoplasia patients will never be normal; right off the bat they have ataxia with a head tremor, truncal ataxia, symmetrical hypermetria, spasticity and broad-based stance
CCA: normal for a period of time and then become abnormal. early onset and progressive but NOT AT BIRTH!!
need a GOOD HISTORY FROM THE OWNER
54
in what breeds is cerebellar cortical abiotrophy inherited in?
airedale, border collie, gordon setter
arabian, gotland pony
holstein, hereford, angus
marino, coriedale
yorkshire pigs
55
what is the poster child for cerebellar cortical abiotrophy?
arabian horses
56
what is chiari-like malformation?
- cerebellar deformities commonly associated with hydrocephalus, and meningomyelocele secondary to spinal bifida
- CAVALIER KING CHARLES SPANIEL
57
what breed gets chiari-like malformations?
cavalier king charles spaniel!!
too much brain and too little skull
58
what chiari-like malformations do CKCS get?
mismatch between caudal fossa volume and brain parenchyma mass = caudal herniation of cerebellar vermis and brainstem into the foramen magnum
59
how can chiari-like malformations lead to syringomelia?
- alteration in CSF flow between intracranial and spinal compartments and reduced craniospinal compliance can lead to syringomelia
- many times not clinically significant
- seen in other toy breed dogs
60
biochemical defects
- not structural defects; won't see anything grossly with 1 exception
- most are "lysosomal storage diseases"
- autosomal recessive, gene dose dependent
- accumulation of uncatabolized substrates within lysosomes = leads to cell dysfunction
- clinical signs at birth or may develop in juvenile or young adults
61
homozygotes with lysosomal storage diseases will ___________
manifest disease
62
heterozygotes with lysosomal storage disease are ______
phenotypically normal, but have 50% of normal enzyme activity. can detect carriers by measuring serum enzyme activity
63
what are histologic features of lysosomal storage diseases?
finely vacuolated cytoplasm; nucleus gets pushed off to the side. neurons with finely vacuolated cytoplasm is common (glial cells, macrophages, renal cells, hepatocytes)
64
what is the unique lysosomal storage disease?
ceroid lipofuscinosis
65
what is ceroid lipofuscionosis
- clinical signs 1-2 years
- cells actually die: massive necrosis/death of cell type
- typically damage to cerebral cortex, retina and cerebellar Purkinje cells
- dementia, blindness, ataxia
- atrophied regions may have brown tinge *only storage disease with gross lesions
66
what is the only storage disease with gross lesions? what are these?
- ceroid lipofuscinosis
- atrophied regions with brown tinge
- clinical signs within 1-2 years of age
- cerebral cortex, retina and cerebellar Purkinje cells
67
what is the acquired/induced storage disease?
- Swainsonine toxicity: Astragalus + Oxytropis plants = LOCOWEEDS
- INDOLIZIDINE ALKALOID inhibits a-mannosidase enzyme
- cattle, sheep, horses
- microscopic lesions identical to genetic alpha mannasidosis (identical to congenital; need history)
- pregnant animals can transmit to fetus
68
T/F: swainosonine/locoweed toxicity can be transmitted to fetus
true, mothers can abort without seeing signs in adults and fetus gets the disease
