Neurology I Flashcards
most common location for canine glioma?
frontal (inclusive of olfactory) 34%
What immunohistochemical marker is a reliable marker of glial differentiation in biopsy or necropsy samples
olig2
*oligos tend to have strong diffuse immunoreactivity, astros have variable reactivity
Koehler 2018
what lesions are hyperintense on T1?
3 F’s and 4 M’s
F: fat ; slow flow, proteinaceous fluid
M:melanin, methemoglobin, mineralisation,
Magnevist (gadolinium contrast)
20% of dogs with CSM have lesions present at which 2 sites?
C5/6, C6/7
Sharp
What are the primary indications for distraction and stabilization for CSM?
- presence of a traction-responsive lesion
- to relieve nerve root compression
How does long-term clorazepate treatment alter phenobarbital level?
increases phenobarbital level
Adverse effects associated with lomustine treatment for MUO?
leukopenia
severe thrombocytopenia
hemorrhagic gastroenteritis
flegel 2011
GABA binding to GABA-B receptor results in…
opens K+ channels and closes Ca2+ channels –> hyperpolarization
Blades Golubovic 2017
How do inotropic glutamate receptors function? What are examples of inotropic glutamate receptors? (3)
Inotropic - influx of sodium and efflux of potassium through inotropic channel –> depolarization –> AP generation
- AMPA - kainate - NMDA - has a Ca channel that becomes permeable to calcium during local membrane depolarization
Blades Golubovic 2017
what special stain will demonstrate chromatolysis better than H&E?
cresyl violet
T/F: in general, the closer to the cell body the axonal lesion, the more likely is the cell to die
true
What type of chromatolysis is induced in motor neuron degenerations described in various species?
central chromatolysis
_____ ______ is loss of cytoplasmic bulk and reduction in size. When might it be expected?
neuronal atrophy might be expected in situations of permanent loss of synaptic connections (as when axons undergo wallerian degeneration but fail to regenerate)
What is the predominant intermediate filament type expressed in meningiomas?
vimentin
an immunohistochemical panel consisting of _____, ______, and _____ has been proposed for the characterization of canine and feline meningiomas from other neoplasias
- vimentin
- CD34
- E-cadherin
Three external landmarks used to locate the tympanic bulla?
- mandibular symphysis
- caudal border of the mandible
- larynx
3 proposed mechanisms of action of phenobarbital
- increasing neuronal responsiveness to GABA
- antiglutamate effects
- decreasing calcium flow into neurons
Fecal incontinence was ____ times more likely in dogs presented with clinical signs compatible with spinal shock
2x
Mari 2019
What characteristics can be used to differentiate ishcemic myelopathy from ANNPE?
- length and directional pattern of intramedullary hyperintensity of the spinal cord on T2W images - ischemic myelopathy - hyperintense intramedullary lesion is long and ill-defined and has a longitudinal pattern - ANNPE - lesion is short and well-defined with caudoventral to craniodorsal oblique directional pattern originated from the affected intervertebral disc, corresponding NP has normal signal intensity but decreased volume
- finding of meningeal and epidural fat enhancement on T1W FS sequences –> ANNPE
(Specchi 2016)
What is seen on histopathology of extruded material in dogs with ANNPE?
cartilaginous material with areas of variable degeneration consistent with a final diagnosis of extrusion of partially degenerated nucleus pulposus
Falzone, 2016
Mari 2017 (157 dogs with ANNPE, 44 dogs with FCEM) - T/F a significant difference was found between groups for the development of urinary incontinence, presence of persistent motor deficits and time to recovery f
False - no significant difference was found for these variables
T/F: no significant difference between CSF lactate concentrations was found between: dogs with clinical signs and MRI evidence of structural intracranial disease -AND - dogs with clinical signs of intracranial disease and normal MRI
true
Beedicenti 2018
How does CSF TNCC influence survival time in dogs with MUO? relapse rate?
lower CSF TNCC significantly associated with improved survival in dogs with MUO (Oliphant 2017)
Niether CSF TNCC nor protein concentration had an effect on survival time in 148 dogs with MUO (Cornelis 2019)
Lowrie et al 2013 identified an association between abnormal CSF analysis and relapse or poor outcome in 29 dogs with MUO
Studies suggest that ___% of dogs with GME die before being treated
15%
Cornelis 2019
Binding of GABA to GABA-A receptors causes……
what drugs are GABA-A agonists?
binding of GABA to GABA-A receptors causes influx of Cl –> hyperpolarization
benzodiazepines and barbituates work through this manner
MOA of metatropic glutamate receptors?
second messenger system to increase inward currents of Na and Ca2+ –> leads to depolarization
Blades Golubovic 2017
How does increase vs. decrease in MAP alter vascular tone?
increase MAP –> vascular constriction
Decrease MAP –> vascular dilation
What two conditions are associated with atherosclerosis?
Hypothyroidism
primary hyperlipidemia
Which 3 processes are important in primary injury of ischemic cerebrovascular disease
- Failure of Na/K ATPase –> cytotoxic edema
- Failure of aerobic metabolism –> lactic acidosis -> cytotoxicity
- Loss of ionic gradients –> depolarization of resting potential and increased Ca2+ release –> activation of proteases and phospholipases –> membrane damage and
free radical formation
Boudreau 2018
What two processes are key in secondary injury in ischemic cerebrovascular disease?
- Damage to BBB –> vasogenic edema and inflammatory cell infiltrate
- severe endothelial injury “hemorrhagic conversion” occurs = extravasation of all blood components through compromised capillaries
Boudreae 2018
When is contrast enhancement secondary to ischemic cerebrovascular disease most evident?
7-10 days after clinical onset
Boudreae 2018
In dogs with multiple nontraumatic ICH > 5mm, outcome was poor in ___%
70%
What is neurologic claudication?
Lameness/weakness that worsens with exercise and resolves to some degree with rest
Neurologic claudication is due to failure of arterial wall vasodilation in affected nerve roots during exercise
Sharp and Wheeler
What surgery is recommended to surgically address LS telescoping?
Dorsal fixation-fusion
Sharp and wheeler
2 mechanisms by which proteins/toxins leave the CNS parenchyma?
- perivascular spaces
- diffusion through the pia mater into the subarachnoid space
(Di Terlizzi 2006)
Where is the area postrema located? What is it’s function?
Located on the dorsal surface of the medulla oblongata at the caudal end of the 4th ventricle -chemoreceptor trigger zone for emesis
positioned to detect emetic toxins, changes in plasma osmolality, glucose, and electrolytes
(Di Terlizzi 2006)
What enzyme is increased in lymphoma of the CNS?
LDH
(Di Terlizzi 2006)
what proteins are found in CSF and synthesized intrathecally? (4)
beta/gamma globulins
tau protei
glial fibrillary acidic protein
myelin basic protein
(Di Terlizzi 2006)
What dye is considered the most specific technique for CSF total protein determination? How is this different for dogs?
Pyrogallol red
underestimates CSF total protein in dogs due to 20% lower affinity for globulins than for albumins
(Di Terlizzi 2006)
Name the 4 ligaments involving C1 and 2
- transverse ligament of the atlas
- apical ligaments of the dens (dens to foramen magnum)
- alar ligaments (dens to occipital bones)
- dorsal atlantoaxial ligament (dorsal arch of C1 - spinous processes of C2)
Which area of the brain has the richest blood supply?
Hypothalamus
Kings
the cranial and caudal vertebral body growth plates close at about ___ mos in dogs
11 mos
Sharp
What are the three branches of the vertebral artery associated with the vertebral column?
- dorsal muscular branch (located caudal to the articular processes and can be harmed during cervical hemi)
- ventral muscular branch
- spinal branch
(Sharp)
Blood from the dorsal surface of the forebrain drains into the _____ dorsal deep part of the forebrain drains to _____ ventral surface of the forebrain_____
- Dorsal surface of the forebrain –> dorsal saggital sinus
- Dorsal deep part of the forebrain –> great cerebral vein
- Ventral surface of the forebrain –> dorsal petrosal sinus
Kings
Where is the origin and insertion of the longus colli muscles?
Origin: transverse process (ventral border) of C3 - C6 Insert: Ventral spine of the next preceding vertebrae
The most cranial segment ends on the ventral tubercle of the atlas
Action: flex the neck
What is the main product of retrograde axonal transport?
Lysosomes
(Kings)
What are the 4 “dorsal root ganglia” that primary afferent neurons of the cranial nerves pass through when forming reflex arcs?
1) trigeminal ganglion
2) geniculate ganglion of the facial nerve
3) proximal and distal ganglion of the glossopharyngeal nerve
4) proximal or distal ganglion of the vagus nerve
Kings
What tract is thought to play the role of the spinothalamic tract in domestic animals?
Spinocervical tract = spinocervicothalamic tract
(Kings)
How does the spinothalamic tract vary in domestic mammals from man?
1) poorly defined
2) Multisynaptic
3) tends to be bilateral rather than unilateral
4) the modalities it transmits are uncertain
(king’s)
What histologic lesions are seen in the temporal cortex, hippocampus and piriform one after seizures?
edema
neovascularization
reactive astrocytosis
acute neuronal necrosis
Volk et al
Characteristics of epilepsy in the English Springer Spaniel? (seizure characteristics, age of onset, genetic basis and sex influence)
Partial and generalized seizures
age of onset < 6y old
partially penetrant autosomal recessive or polygenic inheritance No bias
Ekenstedt et al
Characteristics of IE in Petit basset Griffon Vendeen? (seizure characteristics, age of onset, genetic basis and sex influence)
Mostly focal onset, some with secondary generalization
Mean of 2.2y
Likely hereditary basis owing to clustering within litters
no sex bias
ekenstedt et al
Characteristics of epilepsy in Labrador retrievers? (seizure characteristics, age of onset, genetic basis and sex influence)
partial and generalized seizures
onset 1 - 3y, under 4y
polygenic autosomal recessive no sex bias
ekenstedt et al
What are the 2 most common causes for reactive seizures?
Intoxications
Hypoglycemia
brauer et al
What is the MOA of pregabalin?
binds to the α2δ subunit of voltage-gated Ca channel (GABA receptor)
Dewey 2009
What is the half life of pregabalin in dogs?
7h
(Dewey 2009)
Adverse effects of pregabalin in dogs?
ataxia
sedation
elevated liver enzymes
(Dewey 2009)
How does KBr alter thyroid function?
it doesn’t
“therapeutic administration of KBr in dogs was not found to affect thyroid weight or serum TT4/FT4, TT3 or TSH or to cause histologic changes/thyroid gland weight changes”
(Baird-Heinz et al, 2012)
The _____ is buried deeply in the piriform lobe, consists of a complex of nuclei, and is part of the limbic system
Amygdaloid body
(king’s)
Describe the parasympathetic innervation of the mandibular salivary gland
1) Parasympathetic nucleus CN 7 = salvatory nucleus –> CN VII –> chorda tympani -> lingual nerve (Br of V3)
2) Mandibular ganglion
3) Mandibular gland
CN 7 –> CN 5 RG
What afferent pathways are NOT transmitted through the ascending reticular formation?
muscle proprioception
joint proprioception
King’s
_____% of dogs improved postoperatively after FMD w/ cranioplasty
81%
Dewey et al 2007
It is recommended that hypothyroid dogs with vWF and prolonged bleeding times be given thyroid hormone supplementation for _____h prior to surgery
48h
DeRisio et al 2001
What imaging findings are associated with phantom scratching in the CKCS?
mid-cervical syrinx with a transverse width greater than 4mm
-and/or-
syrinx extension to the region of the superficial dorsal horn
Knowler et al 2018
What clinical signs can be observed in dogs that develop spinal cord damage from syrinx?
scoliosis, weakness, proprioceptive deficits
Knowler et al 2018
T/F: There was a mismatch or rearrangement of neural parenchyma with SM-affected dogs?
True
Knowler et al 2018
How does head position alter imaging findings in dogs with CM/SM?
- no difference in volumetric measurement of the neural parenchyma with changes in head position during MRI
- The CSF space between the cerebellum and brainstem was larger in the flexed position
Knowler et al 2018
Both pain and syrinx size are positively correlated with….
Syrinxes located in the dorsal half of the spinal cord
Knowler et al 2018
The presence of a CSF flow void in the mesencephalic aqueduct associated with ventricular enlargement and SM in dogs suggests….
CSF turbulence and possibly reduced intracranial compliance
Knowler et al 2018
What is different about the development of the spheno-occipital synchondrosis in CKCS and brachycephelic breeds?
Early closure (even earlier in CKCS) \*suspected to be result in basicranium
The ______________ ____________ ____________ cells which delaminate from the dorsal neural tube, contribute not only to the peripheral nervous system, but also to the ectomesenchymal precursors that underpins the cranial skeleton and thus the potential to influence irregularities associated with CM
The multipotent neural crest cells which delaminate from the dorsal neural tube, contribute not only to the peripheral nervous system, but also to the ectomesenchymal precursors that underpins the cranial skeleton and thus the potential to influence irregularities associated with CM
Knowler et al 2018
What is the definition of atlanto-occipital overlapping?
ingavination of the odontoid process into the foramen magnum with ventral brainstem compression
Knowler et al 2018
Is medullary kinking, or dorsal spinal cord compression more strongly associated with CM/SM-related clinical signs?
Medullary kinking significantly higher in dogs with CM/SM related clinical signs
No statistical difference was detected in dorsal spinal cord compression between the 2 groups
Kiviranta et al 2017
drawback to ultrasonic aspirators for resection of intra-axial masses?
- heat and vibration generated during use may damage adjacent normal parenchyma or cranial nerves
- neoplastic cells may be aerosolized and seeded to other areas of the brain
Packer and McGrath 2020
What is the histopathologic finding associated with meningeal fibrosis in pugs?
circumferential meningeal fibrosis with concomitant focal, malacic destruction of the neuroparenchyma in the thoracolumbar spinal cord in 24/30 pugs
vertebra lesions accompanied the focal spinal cord lesion, and lympho-histiocytic inflammation associated or not to the parenchymal lesion in 43% of the pugs
Rohdin et al 2020
MRI vs. CT for detecting CM and SM - which has best agreement between evaluators. Which is more sensitive? Which is more specific?
MRI - most agreement
MRI - most sensitivity for cerebellar herniation and SM
MRI and CT have equal specificity for identifying cerebellar herniation
CT - more specific for identifying SM
Weber et al 2020
What % of patients improved after C-LOX distraction/stabilization for CCSM?
10/11 (90%)
King et al 2020
What are the signs and progression seen in Cocker Spaniels with neuronal abiotrophy?
Onset of signs at 1 year old, disease progresses slowly over several months
Dewey
What neurochemical changes occur in the aging brain and are thought to contribute to cognitive impairment?
decline in: acetylcholine, dopamine, norepinephrine, serotonin, and GABA
increase in: acetylcholinesterase, MOA B
CSF: elevated lactate, pyruvate, and potassium
Dewey
Potential causes for Congenital hydrocephalus? (5)
1) intraventricular hemorrhage (dystocia related)
2) viral infections (parainfluenza in digs, coronavirus in cats)
3) Teratogen exposure
4) Nutritional deficiencies (vitamin A)
5) heritable malformations
Dewey
What is convection-enhanced delivery of chemo for brain tumors?
infusion catheter inserted into the region to be treated
the chemotherapeutic agent is infused via the catheter through the interstitial spaces under a pressure gradient
(Dewey)
MRI findings associated with clinically relevant hydrocephalus? (7)
Elevation of the corpus callosum
Dorsoventral flattening of the interthalamic adhesion
Periventricular edema
Dilation of the olfactory recesses
Thinning of the cortical sulci and/or subarachnoid space
Disruption of the internal capsule adjacent to the caudate nucleus
Ventricle/brain-index - significantly higher in dogs with relevant hydrocephalus
(Laubner 2015)
What is the “hydrodynamic theory” of congenital hydrocephalus?
Hydrocephalus develops due to abnormal (reduced) intracranial compliance
Hydrocephalic patients are believed to have poor intracranial compliance –> increased capillary pulse pressure –> pulsatile transmantle pressure gradient directed from the cerebral tissue toward the lateral ventricles –> rebound pressure from recurring gradient as well as hyperdynamic CSF flow in the mesencephalic aqueduct leads to progressive ventricular enlargement.
Dewey
*abnormal capillary pulsations occur within normal mean ICP
The ______________ ____________ ____________ cells which delaminate from the dorsal neural tube, contribute not only to the peripheral nervous system, but also to the ectomesenchymal precursors that underpins the cranial skeleton and thus the potential to influence irregularities associated with CM
The multipotent neural crest cells which delaminate from the dorsal neural tube, contribute not only to the peripheral nervous system, but also to the ectomesenchymal precursors that underpins the cranial skeleton and thus the potential to influence irregularities associated with CM
Knowler et al 2018
Name 5 anomalous/developmental encephalopathies?
- Congenital hydrocephalus
- Caudal occipital malformation syndrome
- Intracranial arachnoid “cyst”
- Neuronal migration disorders Dandy-walker syndrome
- Miscellaneous malformations
Dewey
in globoid cell leukodystrophy, the deficient enzyme leads to the accumulation of ______ which is toxic to which cells?
in globoid cell leukodystrophy, the deficient enzyme leads to the accumulation of psychosine (splingolipid) which is toxic to
oligodendrocytes and Schwann cells
White matter in the CNS and PNS are affected
(Dewey)
The natural course of paroxysmal dyskinesia is self-limiting in which two breeds of dogs?
labrador retrievers
JRT
32% of dogs undergoing spontaneous remission
75% of dogs showing marked improvement
T/F: study on chihuahuas with CM/SM found that the width of syrinx is associated with clinical signs?
False
Kiviranta et al 2017
Causes of thiamine deficiency in cats? Dogs?
Cats - feeding all fish diet (high in thiaminase)
Dogs - overcooking canned food or meat (heat destruction of thiamine), meat preserved with sulfur dioxide, possibly amprolium induced?
(Dewey)
What are the second and third most common feline brain tumors?
1) meningioma 2) multicentric lymphoma 3) Pituitary tumor
(Dewey)
What two CCJ abnormalities are thought to play an important role in the pathogenesis of SM and neuropathic pain in chihuahuas
medullary elevation dorsal spinal cord compression
What are the two forms of gliomatosis cerebri?
Type I (more common) - diffusely infiltrative form. No mass effect Type II - mass lesion in addition to diffuse neoplastic infiltration Dewey
Underlying cause for organic acidurias?
inherited (usually autosomal recessive) deficiencies of mitochrondrial respiratory chain enzymes (some involve cytosolic enzymes) - enzyme deficiency leads to accumulation of 1+ organic acids - organic acids accumulate in serum, CSF or urine - differ from mitochondrial encephalopathy in the presence of accumulation of organic acids in the urine and other body fludis
(Dewey)
T/F: The brain has glycogen stores
FALSE
(Dewey)
Experimental studies have shown that ______ of the ventricles dilate first in dogs with internal hydrocephalus
temporal horns
(Laubner et al 2018)
What is the prognosis for cats with acquired MG that do NOT have a cranial mediastinal mass?
Excellent!
retrospective case series n=8 - all cats achieved immune remission within 6 mos. 4 cats received no treatment
Megnan et al 2020
Does mean F-wave duration correlate with clinical grade of IVDH in dachshunds?
Yes - mean F-wave duration is well correlated with clinical grade of IVDH
Okuno 2020
how can ketamine have anticonvulsant properties? dexmedetomidine?
Ketamine - decreases excitatory glutamate activity. Also neuroprotective
Dex - decreases sympathetic stimulation and attenuates noradrenaline release. Cerebral vasoconstriction - reduce cerebral edema?
Gioeni et al
Stress and exercise have been identified as a trigger for paroxysmal dyskinesia in which two breeds of dogs? Which breed tends to have episodes at rest?
Norwich Terriers and Maltese - stress/exercise
Border terriers - episodes occur mainly at rest
How does occipital bone volume vary between CKCS w/ and w/o SM and French Bulldogs?
No difference in volume –> does not support theory of occipital bone hypoplasia
Rusbridge et al 2018
in Rohdin et al paper RE 30 pugs with TL myelopathy, what region were most meningeal fibrosis lesions found in?
T5-L1
Leakage of ________has been shown in clinically normal pugs, and is suggested to be the result of a breed-specific astrocyte fragility
GFAP
Rohdin et al 2020
How is neuropathic pain evaluated objectively?
measure mechanical sensory threshold
What two breeds are reported to suffer from cervical IVDH at multiple sites?
Shih tzus and Yorkshire Terriers
Guo et al 2020
Which micro RNAs can *potentially* be used to differentiate glioma and other brain diseases?
miR-15b and miR-342-3p
micro RNA = small noncoding molecules that regulate gene expression following transcription
Narita et al 2020
what is “an epileptic seizure that is objectively and consistently evoked by a specific afferent stimulus or by activity of the patient?”
Reflex epilepsy
Does mean F-wave duration correlate with clinical grade of IVDH in dachshunds?
Yes - mean F-wave duration is well correlated with clinical grade of IVDH
Okuno 2020
How does duration of surgery affect outcome in dogs with absent pain perception treated surgically for TL IVDH?
- Median anesthesia duration in dogs that regained ambulation within 1 year of surgery was significantly shorter than those that did not
- significant negative association between both duration of surgery and total anesthesia time and ambulation at one year, when controlling for body weight and number of disc spaces operated on
Fenn, 2020
What craniocervical junction abnormalities are risk factors for SM?(5)
atlanto-occipital overlapping
atlantoaxial subluxation
dorsal angulation of the dens
occipital dysplasia
atlantoaxial axial “banding”
in globoid cell leukodystrophy, the deficient enzyme leads to the accumulation of ______ which is toxic to which cells?
in globoid cell leukodystrophy, the deficient enzyme leads to the accumulation of psychosine (splingolipid) which is toxic to
oligodendrocytes and Schwann cells
White matter in the CNS and PNS are affected
(Dewey)
Name 5 anomalous/developmental encephalopathies?
- Congenital hydrocephalus 2. Caudal occipital malformation syndrome 3. Intracranial arachnoid “cyst” 4. Neuronal migration disorders Dandy-walker syndrome 5. Miscellaneous malformations
Dewey
2 mechanisms that result in leukodystrophy?
Abnormal synthesis of myelin in the CNS Abnormal maintenance of myelin in the CNS
Rare, poorly understood, heritable, progressive diseases
Dewey
what physiologic processes are thought to contribute to CDS?
increased oxygen free radical mediated cellular damage decreased endogeneous antioxidant edfenses inflammation decreased mitochondrial function
DNA damage
altered gene expression
vascular compromise
decreased capacity for neurogenesis
synaptic dysfunction
neurotransmitter imbalance
Dewey
An interthalamic adhesion diameter of less than ____ mm was found to be consistent with a diagnosis of CDS in dogs
5mm
Dewey
What is thought to be the underlying cause for the development of intracranial arachnoid fluid accumulation?
split of the arachnoid membrane during embryogenesis - aberration of CSF flow from the choroid plexuses during development forces a separation within the forming arachnoid layer - fills w. fluid (identical to CSF)
Dewey
What is the average ate of onset of clinical signs in dogs with IAC?
4y
2m - 10y reported - prosencephalic signs - central vestibular signs - neck pain
Dewey
T/F: notrosourea chemotherapy drugs easily cross the BBB?
True high lipid soluble alkylating agents that cross BBB readily
(Dewey)
In one large study, it was found that ___% of canine intracranial meningiomas had aggressive histologic grade tumors
43% (Dewey)
An ____ CSF level of uric acid and glutamate have been demonstrated in dogs with primary brain tumors
increased
uric acid is an indicator of oxidative injury and potential glutamate excitotoxicity
(Dewey)
In animals that die due to thiamine deficiency, characteristic bilaterally symmetric lesions (petechial hemorrhages) are appreciable throughout the brain at necropsy, especially in the _____
IIn animals that die due to thiamine deficiency, characteristic bilaterally symmetric lesions (petechial hemorrhages) are appreciable throughout the brain at necropsy, especially in the caudal colliculi of the midbrain
(Dewey)
What breed of dog and breed of cat appear predisposed to developing CNS cryptococcosis?
American Cocker Spaniels Siamese cat
(Dewey)
Recent study of 34 cats undergoing surgery for PSS - what percentage experienced post-operative seizures?
23%
Valiente 2020
T/F: study on chihuahuas with CM/SM found that the width of syrinx is associated with clinical signs?
False
Kiviranta et al 2017
Proposed mechanism for clinical signs caused by CCJ abnormalities?
compression of the spinal nucleus and tract of CN V
- receives sensory input related to nociception and temp from the skin/mm of the head
- continues as the substantial gelatinosa and dorsolateral fasiculus in the spinal cord
Kiviranta et al 2017
CM and SM have a _____ mode of inheritance with ______ penetrance in CKCS
polygenic mode of inheritance with variable penetrance
Kiviranta et al 2017
drawback to ultrasonic aspirators for resection of intra-axial masses?
- heat and vibration generated during use may damage adjacent normal parenchyma or cranial nerves - neoplastic cells may be aerosolized and seeded to other areas of the brain
Packer and McGrath 2020
What factors contribute to brain shift (concerning neuronavigation systems)
release of pressure created by presence of a space-occupying mass effects of gravity volume loss of CSF or blood during the procedure differences in animal positioning from imaging to surgery administration of mannitol size of craniotomy defect tumor size tumor type
Packer and McGrath 2020
What percent of cerebrovascular accidents were misinterpreted as gliomas?
10 - 47%
Gutmann 2020
in Rohdin et al paper RE 30 pugs with TL myelopathy, what region were most meningeal fibrosis lesions found in?
T5-L1
MRI vs. CT for detecting CM and SM - which has best agreement between evaluators. Which is more sensitive? Which is more specific?
MRI - most agreement MRI - most sensitivity for cerebellar herniation and SM MRI and CT have equal specificity for identifying cerebellar herniation CT - more specific for identifying SM
Weber et al 2020
how can ketamine have anticonvulsant properties? dexmedetomidine?
Ketamine - decreases excitatory glutamate activity. Also neuroprotective
Dex - decreases sympathetic stimulation and attenuates noradrenaline release. Cerebral vasoconstriction - reduce cerebral edema?
Gioeni et al
What do F-waves represent?
muscle action potentials resulting from excitation of the alpha-motor neurons after antidromic stimulation of a peripheral motor nerve
Okuno 2020
What noninvasive measures can be used to estimate ICP?
MRI
Transcranial doppler ultrasonography
Optic nerve sheath diameter
Giannasi 2020
What atypical MRI features for glioma should raise concern for a granuloma? (4)
- Mixed intra and extra-axial features
- T2W hypointensity without apparent hemorrhage
- Concomitant meningeal enhancement - Minor contralateral lesions
Diangelo et al 2020
What pattern of PET imaging is seen in the normal spinal cord?
Increased SUVmax values at the spinal cord intumescences
SUVmax = standardized uptake values
French 2019
Name 5 anomalous/developmental encephalopathies?
- Congenital hydrocephalus
- Caudal occipital malformation syndrome
- Intracranial arachnoid “cyst”
- Neuronal migration disorders Dandy-walker syndrome
- Miscellaneous malformations
Dewey
MRI findings associated with clinically relevant hydrocephalus? (7)
Elevation of the corpus callosum
Dorsoventral flattening of the interthalamic adhesion
Periventricular edema
Dilation of the olfactory recesses
Thinning of the cortical sulci and/or subarachnoid space
Disruption of the internal capsule adjacent to the caudate nucleus
Ventricle/brain-index - significantly higher in dogs with relevant hydrocephalus
(Laubner 2015)
Enlargement of the ____ nerves is often palpable in dogs with fucosidosis
ulnar nerves (due to edema and infiltration with lipid-filled phagocytes and Schwann cells)
Dewey
clinical signs of neuronal vacuolation and spinocerebellar degeneration in Rottweilers and Boxer Dogs?
-generalized weakness, cerebellar ataxia inspiratory stridor due to laryngeal nerve dysfunction -congenital ocular abnormalities (cataracts, persistent pupillary membrane, microophtlamia, retinal dysplasia) - signs worsen over weeks, end stage - behavior changes
Dewey
What is the “hydrodynamic theory” of congenital hydrocephalus?
Hydrocephalus develops due to abnormal (reduced) intracranial compliance
Hydrocephalic patients are believed to have poor intracranial compliance –> increased capillary pulse pressure –> pulsatile transmantle pressure gradient directed from the cerebral tissue toward the lateral ventricles –> rebound pressure from recurring gradient as well as hyperdynamic CSF flow in the mesencephalic aqueduct leads to progressive ventricular enlargement.
Dewey
*abnormal capillary pulsations occur within normal mean ICP
epidermoid and dermoid cysts are thought to be due to a failure of complete separation of _____ from _____ during embryogenesis
epidermoid and dermoid cysts are thought to be due to a failure of complete separation of neuroectoderm from non-neural (epithelial) ectoderm
if the epithelial ectoderm has adnexal structures, the structure is called a dermoid cyst. If the epithelial ectoderm does NOT have adnexal structures, the structure is called a epidermoid cyst
(Dewey)
What is the average ate of onset of clinical signs in dogs with IAC?
4y
2m - 10y reported - prosencephalic signs - central vestibular signs - neck pain
Dewey
How does hypernatremia affect brain parenchymal cells?
HyperNa –> shrinkage of brain parenchymal cells –> stretching/tearing of small intracranial blood vessels –> hemorrhage Chronic hyperNa (increased osmolality) –> brain parenchymal cells produce idiogenic osmoles
(Dewey)
How can CSF be used to differentiate choroid plexus papilloma from choroid plexus carcinoma?
carcinoma more likely to have CSF > 80mg/dL
Dewey
Dogs with supratentorial masses had a median survival of ____ days whereas those with infratentorial masses had a median survival of ____ days
Dogs with supratentorial masses had a median survival of 178 days whereas those with infratentorial masses had a median survival of 28 days
(Dewey)
There is a ____ association with proliferative cell nuclear antigen (PCNA) level and the likelihood of canine brain tumor reoccurrence, and a ___ association with PCNA level and level of tumor progesterone receptors.
There is a positive association with proliferative cell nuclear antigen (PCNA) level and the likelihood of canine brain tumor reoccurrence, and a negative association with PCNA level and level of tumor progesterone receptors
(Dewey)
What species of aspergillus is most frequently associated with systemic aspergillosis in dogs?
A.terreus
A. fumigatus and A. flavus usually cause localized disease in the nasal cavity A. deflectus and A. niger are reported to cause disease in dogs
Schultz 2008
Causes of false positive Aspergillus Galactolamman ELISA? Causes of false negative?
False-positive - plasmalyte administration, other systemic mycoses False-negative - localized pulmonary involvement
Garcia 2012
The EEG signal is modified by 4 factors
- electrical conductive properties of the tissues
- distance between the electrical source and recording electrode on the scalp
- conductive properties of the electrode
- the orientation of the cortical generator to the recording electrode
Brain Camp Lecture
Indications for running EEG? (4)
- Seizure disorder
- Sleep disorder
- evaluate cerebral function in comatose or obtunded patients
- distinguish seizures from syncopal episodes or paroxysmal dyskinesias
- sheets/streams of neoplastic w/ fibrillary stroma 2. abundant polygonal or elongate eosinophilic cytoplasm w/ indistinct cell margins, finely stippled chromatin, 1 - 2 nucleoli typical features or?
astrocytoma
how to differentiate high-grade from low-grade oligodendroglioma and astrocytoma?
- microvascular proliferation
- necrosis
Koehler 2018
T/F: severe articular process changes or vertebral body malformations raise the index of suspicion for CSM?
True
Sharp
oligodendrogliomas are primarily in gray or white matter?
gray matter. Typically compact, focally infiltrative
koehler 2018
T/F, the degree of infiltration does not determine low vs. high grade astrocytoma
false
- sheets of neoplastic cells w/ basophilic fibrovascular stroma 2. neoplastic cells w/ eosinophilic cytoplasm w/ artifactual perinuclear clear halo 3. oval nuclei w/ dense/coarse chromatin typical of what neoplasm?
oligodendroglioma
What is CNPase?
myelinating enzyme specific to oligodendrocytes and schwann cells, can be used to differentiate oligo vs. astro in BIOPSY samples
Koehler 2018
What is a rathke’s cleft cyst?
Benign cystic lesions
Derived from the remnants of the epithelium embryologically lining Rathke’ s cleft (craniopharyngeal duct
Only ____ _____ with necrotizing meningoencephalitis (NME) showed elevated serum GFAP concentrations (<0.01 to 1.14 ng/ml ), while other breeds of dogs with NME did not
Only Pug dogs with necrotizing meningoencephalitis (NME) showed elevated serum GFAP concentrations (<0.01 to 1.14 ng/ml ), while other breeds of dogs with NME did not
MIYAKE, J-STAGE, 2013
traction-responsive CSM lesions are most likely to respond to which surgical procedures?
distraction-stabilization
traction response suggests compression by anulus fibrosus or ligamentous tissue
traction non-responsive CSM lesions are most likely to respond to which surgical procedures?
ventral slot or dorsal decompression
usually caused by new bone formation or extrusion of nucleus pulposus
___% of dobermans in the US have a bleeding tendency related to VW diesase
16%
Sharp
Mean BMBT for dog is _____
2.62 minutes w range of 1.7 - 4.2 min
surgically treated CSM with associated disc protrusion found an ____% short-term success rate with ___% having significant reocurrence after long-term follow up
surgically treated CSM with associated disc protrusion found an
80% short-term success rate with 20% having significant reocurrence after long-term follow upon
About ___% of dogs undergoing single level decompression (ventral slot) for CSM suffer a second episode of neurological signs within 2 - 3 years.
30%
Sharp
What are the choices of prophylactic procedure for adjacent disc spaces after ventral slot in patient w/ CSM?
- cancellous bone graft at the adjacent space combined w/ forage of ventral cortical bone (aim is to promote fusion)
- place a cement plug at the adjacent space (may increase collapse at slotted space causing foraminal narrowing)
T/F: fenestration is a suitable treatment for any dog w/ CSM
false - it hastens intervertebral collapse and anular buckling - causes spinal cord compression
Sharp
transport of 25nm vesicles in the anterograde direction by a “fast” transport system is fueled by which enzyme?
kinesin - ATPase - moves @ 20 - 30mm/h - enzyme is intricately associated w/ neurotubules
T/F: mitochondria are transported within a neuron via slow transport?
false - moved by a fast transport system
what three locations in the brain are known to have continuous postnatal generation of neurons?
- olfactory bulb “rostral migratory stream”
- hypothalamic-hypophyseal connections (median eminence)
______ canine maningioma have thin-walled capillary and sinusoidal vascular spaces and is rich in reticulin. Can also have small capillary vessels, and interstitial cells which are vacuolated and swollen with lipid
angioblastic meningioma
Type of meningioma?
Microcystic meningioma, with clear and vacuolated tumour cell cytoplasm
Montoliu et al 2006
a significant elevation in _____ acid in the CSF of dogs with confirmed intracranial meningioma
uric acid - significance unknown
Platt et all 2006
______ _____ is a bone erosion caused by pressure atrophy with subsequent thickening due to invasion of the haversian canals by tumor cells
Tumor-related hyperostosis
uncommon phenobarbital associated side effects reported in cats? (5)
facial pruritus
generalized pruritis
distal limb edema
thrombocytopenia
leukopenia
Paraplegic dogs with ANNPE are ____ more times likely to develop urinary incontinence and ____ more times likely to develop fecal incontinence (compared to nonparaplegic dogs)
Paraplegic dogs with ANNPE are 3x more times likely to develop urinary incontinence and 4x more times likely to develop fecal incontinence (compared to nonparaplegic dogs)
Mari 2019
What subgroup of dogs are predisposed to GME? NE?
middle-aged toy and terrier breeds are predisposed to GME
NE predominantly affects younger toy and small breed dogs
___% of dogs diagnosed with GME presented with neurological deficits suggestive of a myelopathy
8%
Granger 2010
4 diagnostic criteria for MUO proposed by Granger et al
- older than 6m
- multiple, single or diffuse intra-axial hyperintensities on T2W MRI images
- pleocytosis on CSF analysis with > 50% monocytes/lymphocytes
4) rule out infectious diseases commonly occurring in the specific geographic area
Most common MRI abnormalities reported in dogs with NME?
- asymmetrical, multifocal
- located in the forebrain
- hyperintense on T2W and FLAIR images
- affect the cortical grey and subcortical white matter (loss of grey/white matter demarcation)
- variable degrees of contrast enhancement of the parenchymal lesions on T2W post-contrast images
(Cornelis 2019)
how does time from onset of signs to presentation alter survival time in dogs with MUO?
significantly longer MST was recorded in 25 dogs that were presented within 7 days of onset of clinical signs, compared to those presented after more than 7 days
Barnoon 2016
what findings on MRI in dogs with MUO are significantly associated with increased risk of mortality? (3)
Mass effect
loss of identifiable cerebral sulci
foramen magnum herniation
Lowrie 2013, 2016
Despite the initiation of appropriate and aggressive immunosuppressive treatment, ___% of dogs in one study died or were euthanized because of MUO, and ___% of these dogs did so within 3d after diagnosis
Despite the initiation of appropriate and aggressive immunosuppressive treatment, 56% of dogs in one study died or were euthanized because of MUO, and
33% of these dogs did so within 3d after diagnosis
Status epilepticus can shorten a dog’s lifespan by about ___ years due to the increased likelihood for euthanasia
2 years
Saito et al
a ____ (positive/negative) correlation between CSF GLU:GABA ratio and seizure frequency difference was found in dogs with idiopathic epilepsy
negative
Podell 1999
where is an eccentric nerve nucleus normal?
large cells of the periventricular gray matter (mesencephalic nucleus of the trigeminal nerve and the olives)
*these cells tend to have a “chromatolytic appearance”
A (higher/lower) risk for development of epileptic seizures and SE has been found in spayed females compared to intact females
higher
Blades Golubovic 2017
In a study of ischemic stroke in dogs, approximately ____ % of patients died within the first 30 days
25% died within 1st 30 days
those that survived first 30 days had MST of 505 days
Gredal 2013
What is the significance of nuclear margination and loss of staining affinity within the nerve cell body?
nonspecific degeneration
*neuronal nucleus is usually single and centrally located
If a neuron dies, surviving neurons with which it has synaptic connections may regress due to lack of activation, undergo atrophy and eventually die - this process is called ___________ __________
transynaptic degeneration
________ is a change in appearance of the soma, brought about by dispersal of the rER
chromatolysis
______ _______ is often seen bulbo-spinal motor neurons and sensory neurons whose peripherally projecting axons are injured and especially when the injury occurs close to the cell body
central chromatolysis
______ ______ has been termed the axon reaction and represents an anabolic adaptive response to axonal injury
central chromatolysis
- represents a shift in metabolic activity towards synthesis of structural cellular proteins and decline in synthesis of transmitters
______ _______ indicates clearing of the periphery of the soma with Nissl granules persisting around the nucleus
peripheral chromatolysis
_____ necrosis involves liquefaction of the nucleus without phagocytosis
ischemic
- may be seen in the ecerebral cortex in hypoxia, hypoglycemia, thiamine deficiency encephalopathy, intoxications (organomercurialism, salt)
- may be seen in the dentate gyrus of the hippocampus and cerebellar purkinje neurons following seizures
excessive stimulus by an excitatory neurotransmitter leading to neuronal degeneration and death is called ________
excitotoxicity
canine meningiomas are derived from _____ ____ cells
arachnoid cap cells (arachnoid granulations)
*particularly where arachonid cells project into dural sinus
ventricular meningiomas are presumed to arise from the _____ _____
tela choroidea (pia mater of the choroid plexus)
_____ subtype of canine meningioma contains nests and lobules of neoplastic meningothelial cells delineated by fine collagenous fibers.
meningothelial (AKA syncytial) types
_____ canine meningioma have interlacing bundles of slender fibroblastic cells
fibroblastic meningioma
______ canine meningiomas have concentric whorls of cells
transitional form (admixture of syncytial and fibroblastic meningioma)
a _____ canine meningioma has small whorls of neoplastic cells and blood vessels that become hyalinized and encrusted with calcium salts - forms _____ body
psammomatous meningioma - forms psammoma body
in ______ canine meningiomas individual lobules of a meningioma undergo a spongy vacuolar change producing a cribiform appearance
microcystic
T/F: metastasis of intracranial meningioma has never been reported in the dog?
False - metastasis to the lungs has been reported in 3 dogs
T/F: labelling for S100 is common in meningiomas?
True 90% (n=30) in Montoliu et al (2006)
type of meningioma?
Angiomatous meningioma. Note the presence of thin-walled vascular spaces and haemorrhages
Montoliu et al 2006
Type of meningioma?
Papillary meningioma. Meningothelial cells grow perpendicularly to the surface of fibrovascular strands
Montoliu et al 2006
Type of meningioma?
Anaplastic meningioma, with scattered mitoses and moderate pleomorphism
Montoliu et al 2006
Type of meningioma?
Optic nerve meningioma with areas of cartilaginous and myxoid metaplasia
Montoliu et al 2006
Type of meningioma?
Transitional meningioma located in the spinal cord. Note the presence of cartilaginous metaplasia
Montoliu et al 2006
How strongly do canine meningiomas stain with NSE (neuron specific enolase)?
variable
Montoliu et al 2006
Do canine meningiomas commlnly show CK expression or GFAP expression?
no
Montoliu et al 2006
meningiomas exhibit differentiation of what two embryonic cell lines?
mesenchymal and epithelial differentiation
T/F: MMP-2 and MMP-9 expression by tumor cells is not predictive of the formation of peritumoral edema in canine rostrotentorial meningiomas?
T
Beltran et al 2013
Which type of meningioma is most likely to act malignant?
anaplastic
what two feline diseases can mimic the appearance of a meningioma?
Toxoplasmosis, cryptococcosis
T/F: > 40% of canine meningiomas are atypical (grade II)
True
(a mitotic index > 4/10HPF and brain invasion are sufficient criteria to identify grade II meningiomas)
T/F: more aggressive and atypical meningiomas are more likely to express progesterone receptors in dogs
False - more aggressive/atypical meningiomas are LESS likely to express PR
What is the MOA of hydroxyurea?
- antimetabolite that specifically affects the S stage of the cell cycle
- Inhibits the growth of slow growing tumors
What are the two superficial muscles encountered during approach to VBO?
platysma and sphincter colli
what vascular/nervous/salivary structures are encountered during approach to VBO?
- mandibular salivary gland
- lingofacial and maxillary veins
- hypoglossal nerve
- lingual artery
what are the deep muscles that are dissected during approach to VBO?
- digastricus
- mylohyoid
- hyoglossus
- styloglossus
What structure is housed within the promontory?
The cochlea
Where in the middle ear of the cat are sympathetic fibers most vulnerable to surgical trauma?
promontory
What is the elimination half life of phenobarbital in dogs? cats?
40 - 90h in dogs 40 - 50h in cats (after PO administration)
How does phenobarbital alter TT4, FT4 and TSH?
decreases TT4
decreases FT4
increases TSH WITHOUT inducing clinical signs of hypothyroidism
how does phenobarbital alter adrenal function tests in dogs?
it doesnt
What is the MOA of bromide?
hyperpolarizes neuronal membranes after traversing neuronal chloride channels
What is the elimination half life of KBr in dogs?
24 days
High chloride intake _____ bromide elimination
High chloride intake INCREASES bromide elimination
How should KBr dosing be altered in patient with kidney insufficiency?
renal insufficiency DECREASES KBr elimination dog w/ kidney dz –> LOWER dose of KBr should be used
What are adverse effects of KBr in dogs (besides sedation/ataxia, PU/PD, polyphagia)
hyperactivity
megaesophagus
pruritic skin rash
vomiting
pancreatitis
coughing - rare
What is the elimination half life of clorazepate?
3-6 hrs in dogs
What is the MOA of zonisamide? (2)
blockage of T-type calcium and voltage-gated Na channels binding to the chloride channel associated w/ GABA
How is zonisamide metabolized? what is the half life in dogs?
metabolized by hepatic microsomal enzymes half life in dogs is 15 hrs
MOA of levetiracetam?
binds to SV2A (synaptic vesicle protein) –> altera neuronal calcium flow. exact MOA unknown
What is the elimination half life of levetiracetam in dogs? cats?
4h in dogs, 3h in cats
How is LEV metabolism altered in dogs concurrently receiving phenobarbital?
metabolism is accelerated over time in dogs concurrently receiving phenobarbital
How does taurine deficiency cause blindness?
retinal degeneration
a hyperreflective focal lesion in the area centralis of a cat: likely cause?
taurine deficiency
what vitamin abnormality in the cat can cause muscle soreness and hyperesthesia along the neck and forelimbs?
Vitamin A toxicity
How can FeLV affect the spinal cord?
suspected to cause degenerative myelopathy
T/F: There were significant differences in circulating melatonin, serotonin or dopamine concentrations between dogs with SARDS, PDH and normal dogs
False
Oh. JVIM 2019
T/F fear and anxiety behaviors were significantly reduced under impetoin treatment compared to placebo
true - clinical trial, owners started treatment 2d before the anticipated noisy event
Engel 2019
MOA of imepitoin?
partial agonist of the benzodiazepine-binding site of the GABA-receptor with low affinity –> potentiates neuronal inhibition
Dogs with ANNPE and an intramedullary hyperintensity > _____% of the cross-sectional area of the spinal cord at the same level on transverse images were ____ times more likely to develop urinary incontinence
Dogs with ANNPE and an intramedullary hyperintensity > 40% of the cross-sectional area of the spinal cord at the same level on transverse images were 4x times more likely to develop urinary incontinence
Mari 2019
4 MRI features of ANNPE
- narrowed IVD space + reduced volume of nucleus pulposus located below a focal T2w hyperintense intramedullary spinal cord lesion
- presence of extradural material compatible with hydrated nucleus pulposus at the same level causing minimal or NO spinal cord compression
- the presence of a cleft in the dorsal part of the annulus fibrosis
- the presence of meningeal or epidural contrast enhancement in post-contrast T1W fat-suppressed images
DiRisio 2009 - what % of dogs with ANNPE had a successful outcome?
67%
T/F: detection of intramedullary hypointensity is associated with outcome in dogs with ANNPE?
True
DiRisio - results of multivariate analysis of dogs with ANNPE suggested that _______ was the best predictor of outcome
maximal cross-sectional area of the intramedullary hyperintensity on transverse T2 weighted MR images
Traumatic IVD extrusion with concurrent spinal cord compression is positively associated with what two factors
age and chondrodystrophic breeds
(Henke 2013)
Ros 2017 on ANNPE: 1. Accuracy of myelography to detect site of herniation was ___% and to identify extradural compression was ___% 2. All dogs had an _____ pattern, but an ____ pattern was detected in 57% of cases 3. Based on myelography, reviewers would not have performed surgical decompression in _____% of dogs
- Accuracy of myelography to detect site of herniation was
- 9% and to identify extradural compression was 57% in study by Ros 2017
- All dogs had an intramedullary pattern, but an extramedullary pattern was detected in 57% of cases
- Based on myelography, reviewers would not have performed surgical decompression in 71% of dogs
causes of ischemic myelopathy? (6)
- infectious emboli (bacterial, parasitic)
- neoplastic emboli
- fat emboli
- thrombi
- atherosclerosis
- fibrocartilage emboli
What is the “vaccum phenomenon” as it relates to ANNPE?
gas accumulation within the disc space after herniation of hydrated material
Manunta et al 2015 - 5 dogs tetraparetic/tetraplegic dogs with ANNPE treated conservatively regained ambulatory status within _____
1 month
ANNPE vs. ischemic myelopathy - which feature is characteristic of each 1. older age at disease onset 2. history of vocalization 3. spinal hyperesthesia 4. L4-S3 localization 5. C1-5 localization 6. ambulatory at hospital discharge 7. long-term quality of life/outcome 8. long-term fecal incontinence
- older age at disease onset (ANNPE)
- history of vocalization (ANNPE)
- spinal hyperesthesia (ANNPE)
- L4-S3 localization (IM)
- C1-5 localization (ANNPE)
- ambulatory at hospital discharge (ANNPE)
- long-term quality of life/outcome (good in both provided intact nociception)
- long-term fecal incontinence (IM)
Fenn 2016
Mari 2017 (ANNPE vs. FCE) - fecal incontinence was ____x more likely in dogs with presumptive ANNPE compared with presumptive FCEM
5x more likely with ANNE
ANNPE 23%, FCEM 7.5%
Is CSF lactate concentration associated with… diagnosis NCC protein RBC count survival
no correlation between CSF lactate concentration and diagnosis, RBC count or survival
weak correlations were noted between CSF lactate concentration and:
NCC (absolute large mononuclear cell count, absolute small mononuclear cell count, absolute neutrophil count)
Protein
What is the reference interval for L-lactate in canine CSF?
1-2.5 mmol/L
Nye 2018
How is CSF lactate affected in dogs with age-related cognitive dysfunction?
CSF lactate was significantly higher in dogs with severe cognitive dysfunction than in unaffected and mildly affected dogs
What % of dogs diagnosed with MUO were large breeds?
25%
Cornelis 2016
T/F: recent studies have found females are statistically significantly more likely to develop GME?
false - no statistical significance in female:male ratio in more recent studies
Cornelis 2019
In one study of GME, ___% of dogs had no abnormalities on T2W MRI
7%
Talarico and Schatzberg 2010, Granger 2010
Typical MRI findings in patients with NLE?
- multiple asymmetrical cerebral white matter and brainstem abnormalities
- hyperintensity on T2W and FLAIR images (often with regions of cystic necrosis)
- mimimal contrast enhancement of parenchymal abnormalities
Cornelis 2019
Typical MRI findings in dogs with meningomyelitis of unknown origin?
Multifocal or focal poorly demarcated intramedullary T2W hyperintensities with variable contrast enhancement
Cornelis 2019
Adverse effects associated with procarbazine treatment for MUO?
myelosuppression
hemorrhagic enteritis
Coates 2007
adverse effects reported from treatment with mycophenolate for MUO?
hemorrhagic diarrhea in the first 2 weeks
adverse effects associated with treatment with vincristine and cyclophosphamide for MUO? (3)
myelsuppression hemorrhagic cystitis pyometra
unacceptable to authors, excluded from further investigation
Smith 2009
How is age associated with prognosis in dogs diagnosed with MUO?
younger age at time of diagnosis was significantly associated with improved survival in 52 dogs (Oliphant 2017)
Relapse was recorded in ___% of dogs (n=39) within a median of ____ days after diagnosis (Lowrie 2013)
Relapse was recorded in 65% of dogs (n=39) within a median of 210 days after diagnosis (Lowrie 2013)
Abnormal CSF @ 3m was associated with higher risk of relapse combination of MRI and CSF analysis provided greater sensitivity for predicting relapse than one modality alone discontinuation of treatment before resolution of MRI abnormalities always resulted in relapse
How does intranasal midazolam compare to IV midazolam in treating status epilepticus?
IN route demonstrated superiority when the time needed to place an IV catheter was taken into account
seizure cessation time for IN compared to IV was not significantly different (without IVC placement time)
Charalambous 2019
What is the estimated case fatality rate of dogs that experience status epilepticus?
25.3 - 38.5%
Charalambous 2017
How is CSF GABA concentration correlated with seizure frequency in dogs dogs
lower CSF GABA concentration reduced response to phenobarbital administration
(Podell 1999)
Approximately _____% of dogs with primary epilepsy are refractory to antiepileptic drug therapy
30 - 40%
Podell 1999
What is the MOA of phenobarbital?
binds the GABA-A receptor to:
- directly activate GABA receptor-gated chloride channels
- potentiate GABA-mediated Cl conductance
end result is enhanced hyperpolarization of neuronal membranes
Podell 1999
_____ concentrations of GABA and _____ concentrations of glutamate were present in the CSF of untreated epileptic dogs
Lower concentrations of GABA and higher concentrations of glutamate were present in the CSF of untreated epileptic dogs
Secondary adverse effects of increased autonomic stimulation associated with SE? (7)
- cardiac arrhythmias
- acidosis
- rhabdomyolysis
- hypotension
- shock
- noncardiogenic pulmonary edema
7 acute tubular necrosis
Blades Golubovic 2017
A hereditary basis for epilepsy has been proven in which 9 breeds
- Labrador Retrievers
- German Shepherd dogs
- Golden Retrievers
- Bernese Mountain Dogs
- Belgian Tervurens
- Vizslas
- Keeshonds
- English Springer Spaniel
- Border Collies
approximately ___% of dogs diagnosed with ischemic strokes have concurrent underlying diseases - the 4 most common are?
50% of dogs have underlying systemic disease
- HAC
- CKD
- Hypothyroidism
- Systemic hypertension
Garosi 2005
T/F: There is an association between region of the brain involved in a stroke, type of infarction, and outcome
False
Garosi 2005
Dogs w/ acute ischemic stroke commonly have ___ (elevated/decreased/normal cardiac troponin I
elevated cTn1
level was not different between dogs experiencing good and poor outcomes (small study)
cardiac disease is not considered to be a common underlying cause for ischemic stroke in dogs
Goncalves 2019
Canine arterial cerebrovascular blood supply arises from the ____ and ______ arteries which feed into the cerebral arterial circle. In the cat. Blood flow through the _____ artery is predominantly directed craniocaudally and the ______ artery supplies most of the blood to the cerebral arterial circle.
Canine arterial cerebrovascular blood supply arises from the basilar and internal carotid arteries which feed into the cerebral arterial circle. In the cat. Blood flow through the basilar artery is predominantly directed craniocaudally and the external carotid artery (via maxillary artery) supplies most of the blood to the cerebral arterial circle
Boudreau 2018
total cerebral blood flow should be constant for mean arterial pressures between ____ and ____ mmHg
50 - 150mmHg systolic
CPP < ___mmHg systolic results in ischemia and loss of autoregulation
cerebral perfusion pressure < 40mmHg systolic
Boudreau 2018
What is primary vs. secondary injury related to ischemic cerebrovascular dz
primary injury
-due to energy failure
secondary injury
- due to compromise of local vascular endothelium and supporting cells. Develops ~ 4-6 hrs after onset of hypoperfusion, progresses for 24 - 48h
Boudreau 2018
What is the difference between ischemia and infarction?
ischemia - perfusion reduction sufficient to induce dysfunction in the affected tissue
infarction - perfusion reduction that causes irreversible injury and eventually necrosis
Boudreau 2018
How does PaCO2 alter cerebral vascular tone?
Increased PaCO2 –> cerebral vasodilation
Decreased PaCO2 –> cerebral vasoconstriction
How does cerebral PaO2 alter cerebral vascular tone?
Increased PaO2 –> cerebral vasoconstriction
Decreased PaO2 –> cerebral vasodilation
What regions of the brain are most susceptible to ischemia? (4)
- cerebral cortex (esp. gray matter of the hippocampus)
- cerebellar cortex
- Basal nuclei
- Thalamic nuclei
Boudreau 2018
Which two dog breeds are predisposed to ischemic CVD?
CKCS
Greyhound
Boudreau 2018
3 causes of subdural hemorrhage?
- Trauma
- Chronic hydrocephalus
- Chronic storage disease
Boudreau 2018
What does cerebrovascular ishcemic change look like on CT scan?
mild focal edema
mild mass effect
minimal contrast enhancement
- subtle and nonspecific changes
What does acute cerebrovascular hemorrhage look like on CT scan?
- hyperattenuation relative to gray and white matter (due to globin) - increases for 72h after onset –> then gradually decreases to isoattenuation ~1m post hemorrhage (beginning from periphery and extending inward)
- peripheral contrast enhancement from 6d - 6w post event (d/t neovascularization?)
Boudreau 2018
MRI changes associated with global ischemia?
mild diffuse T2 hyperintensity in the gray matter of the cerebrum, thalamus and cerebellum with mild contrast enhancement of the same regions
Boudreau 2018
T/F: DWI showed ischemic change earlier than conventional MRI sequences in an experimental feline model?
true
Boudreau 2018
The technique of T2* exploits the sensitivity of the GRE sequences to _________
small magnetic field inhomogeneities (like those produced by paramagnetic intracellular deoxyhemoglobin or methemoglobin)
superparamagnetic blood breakdown products may produce GRE artifacts for months to years
Boudreau 2018
CSF in cases of hemorrhagic CVD?
often nonspecific, may be normal
mild increases in protein content or increases in neutrophilic and mononuclear populations
Boudreau 2018
What CSF biomarker is increases in canine models and clinical cases of ischemic stroke?
interleukin 6
Boudreau 2018
In dogs with single nontraumatic intracerebral hemorrhage > 5mm, long term outcome was good in ____%
60%
Boudreau 2018
How does cardiac troponin I concentration change in dogs with recent seizures
serum concentrations of cardiac troponin I were higher in dogs that had recent seizures compared to controls.
The predictors most clearly associated with cardiac troponin I concentration were:
- number of seizures
- age * both positively associated with increasing concentrations of troponin I
Dutton 2017
Garosi et al 2005 - small breed dogs were significantly more likely to have _______ infarcts and large breed dogs were significantly more likely to have _____ infarcts
small breed dogs were significantly more likely to have cerebellar territorial infarcts and large breed dogs were significantly more likely to have lacunar thalamic or midbrain infarcts
How does the presence of a concurrent medical condition in patient diagnosed with brain infarction associated with survival time?
Dogs with concurrent medical conditions had significantly shorter survival times than those with no identifiable medical condition
Dogs with concurrent medical conditions were more likely to suffer from recurrent neurologic signs because of subsequent infarcts
Garosi 2005
How does the sided-ness of an ischemic CVA influence survival time?
right-sided lesions posed a significantly increased risk of mortality with MST in dogs with right-sided lesions of 24 days vs. 602 days in dogs with left-sided lesions
Gredal 2013
What risk factors for repeated stroke has been identified in dogs?
none reported thus far
Gredal 2013
Compressive radiculopathy of the L7 nerve root reportedly occurs in ___% of dogs with DLSS and is associated with clinical signs in ____%
Compressive radiculopathy of the L7 nerve root reportedly occurs in 68% of dogs with DLSS and is associated with clinical signs in 50%
Godde and Steffen 2007
what two factors control rate of CSF formation?
- Weight of the choroid plexi
2) rate of sodium and bicarbonate ion exchange
(Di Terlizzi 2006)
What are the 8 possible components of “lumbosacral disease”
- Stenosis of the vertebral canal
- Hansen type II disc herniation at L7/S1
- subluxation, osteophytosis or thickening of the articular processes
- Epidural fibrosis
- Soft tissue proliferation of the joint capsule or ligamentous structures
- Vascular compromise of the spinal nerves
- Osteochondrosis of the sacrum
- Instability and misalignment of L7/S1
Sharp and Wheeler
EMG of patient with LS disease may show?
LMN disruption –> spontaneous activity
EMG is useful to reduce the number of false + diagnoses associated with MRI evidence of nerve root disorders
Sharp and Wheeler
The subarachnoid space extends beyond the LS junction in about ___% of dogs
80%
Sharp and Wheeler
Indications for surgery in dogs with LS disease?
Nonsurgical treatment has failed
Working dogs
pain or neurological deficits
CT or MRI findings of increased soft tissue suggestive of epidural fibrosis (especially if it enhances with contrast)
T/F: Lateral foraminotomy does not have a good short term and long-term outcome
False
Gomes et al 2018
According to Di Risio et al (2001) what clinical sign of DLSS is most significantly associated with outcome?
Urinary or fecal incontinence
- pre-operative duration of urinary incontinence was the sole temporal variable significantly associated with that outcome - authors concluded that prognosis is guarded in those cases where incontinence (particularly urinary incontinence) exceeds 1 month
what are the names of the 3 foraminal zones?
a) entrance zone b) middle zone c) exit zone
The lateral foraminotomy described by Godde and Steffen was developed to address compressive lesions in which region?
Developed to address compressive lesions within the foramen and at its exit
T/F: Compression of the soft-tissue structures within the vertebral canal at the LS space is associated with severity of clinical signs
false
Mayhew et al 2002
Epidural steroid injection for DLSS - ____% of treated dogs were reported to improve clinically and ____% were considered cured by their owners
79% of treated dogs were reported to improve clinically and 53% were considered cured by their owners
Jeffery 2014
What is the risk of performing an L7/S1 dorsal laminectomy with a foraminotomy?
articular process fracture
Jeffery 2014
What are the goals of fixation-fusion surgery for DLSS?
reduce pain and cauda equina dysfunction by:
- eliminating the dynamic components of nerve compression within the vertebral canal or foramina (fix the bones to prevent motion)
- slightly flex the LS joint –> opens the foramina and decreases annular protrusion
jeffery 2014
How does disc degeneration alter the stability of the lumbosacral region in dogs?
reduced ROM
jeffery 2014
How does CSF pressure change during inspiration and expiration?
Inspiration - CSF pressure rises
Expiration - CSF pressure falls
In pathological ICP elevations, the fluctuations in CSF pressure become very marked
(Di Terlizzi 2006)
IF there is a sudden increase in intracranial blood volume, CSF can be momentarily accommodated into the _____ _______ space because of the elasticity of the dura mater
cervical subarachnoid space
(Di Terlizzi 2006)
Sites of CSF draining/absorption?
- Arachnoid villi –> cerebral veins
- Veins/lymphatic vessels around the spinal nerve roots and spinal nerves
- Veins/lymphatic vessels around CN I and II where they leave the skull
(Di Terlizzi 2006)
3 regions of the brain that lack BBB
- Hypothalamus
- Pituitary gland
- Area postrema
(Di Terlizzi 2006)
what type of cells make up the BBB and blood spinal cord barrier?
non-fenestrated endothelial cells with interendothelial tight junctions
(Di Terlizzi 2006)
What 2 kinds of cells make up the blood-CSF barrier?
1) fenestrated vascular endothelial layer
2) ciliated columnar epithelial choroidal cells w/ basolateral infoldings and apical tight junctions
(Di Terlizzi 2006)
What type of cells make up arachnoid villi? How are toxic substances prevented from entering the CSF from the blood?
- arachnoid cap cells = endothelial cells with tight junctions - valve-like channels collapse when pressure is applied from the venous side and open when CSF pressure increases - creates a SEMIPERMEABLE membrane
(Di Terlizzi 2006)
Experimental studies in dogs have demonstrated that ___% of CSF is derived from the third and lateral ventricles,___% from the fourth ventricle, and ___% from the subarachnoid space
Experimental studies in dogs have demonstrated that 35% of CSF is derived from the third and lateral ventricles, 23% from the fourth ventricle, and 42% from the subarachnoid space
(Di Terlizzi 2006)
The secretion of CSF depends primarily on what process?
Active transport of Na+ ions into the ventricles
(Di Terlizzi 2006)
What process allows absorption through arachnoid villi?
micropinocytotic vesicles
(Di Terlizzi 2006)
What is the typical reference range for protein content in CSF? what is the main protein in CSF?
10 - 40mg/dL for cisternal sample
albumin is the main protein in the CSF, globulins are normally very low
(Di Terlizzi 2006)
What factors determine glucose concentration in CNS?
- blood glucose
- rate of glucose transport into the CSF
- metabolic rate of the CNS
(Di Terlizzi 2006)
T/F: Changes in plasma potassium concentration will significantly alter CSF K+ content
false
CSF K+ concentration remains within normal range across wide range of plasma K+
(Di Terlizzi 2006)
What two enzymes may increase in the CSF when extensive myelin degeneration has occured?
AST and CK (nervous isoenzyme)
(Di Terlizzi 2006)
4 disease processes that can result in blockage of CSF absorption at arachnoid villi
- space occupying lesions - compression of the venous sinuses
- cerebral edema
- meningoencephalitis
- vitamin A deficiency –> arachnoid villi atrophy
(Di Terlizzi 2006)
In which order to cells deteriorate in CSF stored at 4C?
small mononuclear cells
large mononuclear cells
neutrophils
eosinophils
(Di Terlizzi 2006)
What products can be added to CSF to aid stability? (4)
fetal calf serum
hetastarch
foramlin
fresh or frozen autologous clear plasma/serum
(Di Terlizzi 2006)
A CSF NCC of > ___ cells/uL is associated with an increase of turbidity
500
(Di Terlizzi 2006)
What proteins are synthesized in the choroid plexus and found in CSF? (3)
transthyretin retinol-binding protein
transferrin
What is a screening test for the presence of globulins in CSF?
Pandy test
few drops of CSF to 1mL of pandy reagent (10% carboxylic acid). Turbidity indicates the presence of globulin and has a sensitivity of approximately 50mg/dL
(Di Terlizzi 2006)
Which immunoglobulin is not normally found in CSF?
IgM - its presence in serum and/or CSF is considered more specific than IgG or total immunoglobulin levels for detection of active infectious diseases
(Di Terlizzi 2006)
How does CSF MBP vary in dogs with degenerative myelopathy?
increase in CSF MBP concentration in dogs with DM (lumbar cistern)
the same study confirmed a correlation between MBP and the severity of demyelination
What cell type is most abundant in normal CSF in dogs? cats?
dogs - small lymphocyte
cats - macrophages
(Di Terlizzi)
At L6/7 and L7/S1 in the dog, the spinal nerve and main arterial vessel pass through the ____ sub-compartment of the intervertebral foramen and the intervertebral vein passed through the ______ sub-compartment
At L6/7 and L7/S1 in the dog, the spinal nerve and main arterial vessel pass through the cranial sub-compartment of the intervertebral foramen and the intervertebral vein passed through the caudal sub-compartment
The intervertebral foramen contains a fibrous septum dividing it into 2 subcompartments by connecting the fibrous capsule of the articular process joints with the intervertebral disc and the adjoining vertebral body
(Breit et al, 2013)
Surgical options for treating L7/S1 foraminal compression? (4)
- dorsal laminectomy and partial discectomy +/- facetectomy
- unilateral foraminotomy
- distraction/fusion techniques (insertion of an intervertebral cage, insertion of a titanium intervertebral distraction bolt)
- Pedicle screw-rod fixation (+/- flexion)
Smolders et al (2020)
In cadaver study by Smolders et al, did foraminotomy or distraction/stabilization of L7/S1 result in greater volume of the foramen
foraminotomy was more effective in increasing the foraminal volume and especially the cranial subcompartment (where the L7 nerve root traverses the foramen)
The lumbar internal vertebral venous plexus drains into the _____ veins
major veins of the abdomen
- mainly the azygous vein and the caudal vena cava
(Sharp)
What is the difference between myelin figures and myelin fragments when analyzing CSF cytology?
Myelin figures - originate from a nonspecific lipid source. Originate from cell-membrane phospholipids
Myelin fragments - collection of myelin found extracellularly, more indicative of demyelination
foraminal stenosis and compressive radiculopathy of the L7 nerve root has been reported in ____% of dogs affected by DLSS
68% (Mayhew 2014)
Where are the mamillary processes of the thoracic vertebrae located in the thoracic spine? lumbar vertebrae?
thoracic vertebrae - short, knob-like dorsal projections from transverse processes
lumbar vertebrae - dorsal projections of the cranial articular processes
Sharp
Where does a change in orientation of the cranial/caudal articular processes occur in the thoracic vertebrae?
The articular processes from T1 - 10 are in an oblique horizontal plane as in the cervical vertebrae
In the caudal thoracic vertebrae (around the anticlinal) they adopt a more vertical orientation (as in the lumbar vertebrae)
(Sharp)
Right to left: C5, 6, 7
Note the transverse foramen in C5 and C6. The transverse process of C have no foramina and have a characteristic horizontal orientation
(Sharp)
How does arterial supply to the brain vary in dog vs. cat?
Dog - supplied by internal carotid artery and vertebral artery (vertebral artery)
Cat - maxillary blood supplies to all of the brain except the caudal part of the medulla oblongata which is supplied by vertebral blood - the basilar artery carries blood away from the arterial circle
Ox - a mixture of maxillary and vertebral blood reaches all parts of the brain
(KINGS)
Which arterial branches supply the inner zone of the spinal cord? Which branches supply the outer zone?
inner zone - Vertical arteries
Outer zone - radial artery
Kings
What is this called? What cohort of dogs develops it?
leukoaraios
Endplate osteochondrosis
(GENDRON 2012)
Intravertebral disc herniation (Schmorl’s nodes)
(Gendron 2012)
Fatty replacement at the endplate
STIR should null signal
(Gendron 2012)
Describe the perineurium, epineurium and endoneurium
How does the shape and position of the central canal vary between the brainstem and spinal cord?
brainstem cent canal = 4th vent. Tends to be DORSAL and WIDER than the central canal of the spinal cord
The columns of the grey matter become V-shaped when seen transversely. They lie obliquely on either side of the 4th ventricle
(Kings)
How does the anatomy of the grey matter of the brainstem vary from the spinal cord?
How does the anatomy of the grey matter of the brainstem vary from the spinal cord?
What three cranial nerve nuclei contain a special visceral efferent component?
1) motor nucleus of the TG nerve (supplies masticatory m)
2) motor nucleus of the facial nerve (supplies facial m)
3) nucleus ambiguus (supplies pharyngeal and laryngeal muscles)
(Kings)
What is the somatic afferent nucleus called in the brainstem? What are the three divisions of this nucleus? What is the responsibility of each division?
Sensory nucleus of the trigeminal nerve
1) Nucleus of the spinal tract of CN V
2) Principal (pontine) sensory trigeminal nucleus 3) Nucleus of the mesencephalic tract of the trigeminal nerve
Kings
What are the four visceral efferent nuclei of the cranial nerves? What is their homologous structure in the spinal cord?
Parasympathetic nuclei of CN 3, 7, 9, and 10
Homologous to the lateral horn of the spinal cord
Kings
What are the 4 somatic efferent nuclei of the cranial nerves?
Motor nucleus of CN 3
Motor nucleus of CN IV
Motor nucleus of CN VI
Motor nucleus of CN XII
Kings
Morphologic abnormalities associated with CM/SM?
How is atlantooccipital overalapping diagnosed on CT?
How is atlantooccipital overalapping diagnosed on CT?
How is atlantooccipital overalapping diagnosed on CT?
CCJ was considered overlapped when the dorsocranial border of the lamina of the atlas was at the level of the purple line
Kiviranta et al 2017
How is atlantooccipital overalapping diagnosed on CT?
CCJ was considered overlapped when the dorsocranial border of the lamina of the atlas was at the level of the purple line
Kiviranta et al 2017
