Papers/Short answers Flashcards
Diagnostic yield of D-dimers and thromboelastography in diagnosis of canine CVA?
Low
Neither D-dimer concentration nor TEG was significantly associated with a CVA (P = .38 and .2, respectively). D-dimer testing was performed in a low-risk population and showed low sensitivity (30.8%; 95% confidence interval [CI], 10%-61%) and high specificity (86.4%; 95% CI, 64%-96%) for CVA diagnosis. Thromboelastography was performed in a high-risk population and showed moderate sensitivity (64.3%; 95% CI, 44%-81%) and specificity (66.7%; 95% CI, 24%-94%) for CVA diagnosis. Abnormal D-dimer concentration or TEG were not helpful in differentiating hemorrhagic from ischemic stroke (P = .43 and .41, respectively).
Most important clinical and MRI findings in dogs with idiopathic oculomotor neuropathy?
Outcome?
1) unilateral ophthalmoplegia/ophthalmoparesis (internal, external, or both) with the absence of other neurologic and ophthalmic signs - mostly combined 79%, or internal (mydriasis) 21%
2) MRI findings
restricted to the oculomotor nerve (enlargement + contrast enhancement)
3) good prognosis, most cases improving or not deteriorating without therapy
Which breeds are most commonly affected by idiopathic oculomotor neuropathy?
Boxers and border collies
Which CN is affected in this image?
9.5-year-old male entire Staffordshire Bull Terrier
- Mydriasis secondary to internal ophthalmoplegia, and
- upper eyelid ptosis and
- neuromuscular strabismus (ventrolateral) secondary to external ophthalmoparesis of the OS
What is the middle cranial fossa (sinus cavernosus) syndrome?
a paired depression of the basiphenoid bone, located between the rostral and caudal cranial fossa at the base of the skull.
CN III, IV, V, VI travel there and exit the skull through the orbital fissure (oculomotor nerve, trochlear nerve, abducens nerve, and ophthalmic branch of the trigeminal nerve), round foramen (maxillary branch of the trigeminal nerve), or oval foramen (mandibular branch of the trigeminal nerve)
The middle cranial fossa syndrome is a well-recognized syndrome in dogs characterized by variable impairment of these nerves (usually due to neoplastic mass lesion of the middle cranial fossa)
Which medication can cause hypo/anosmia
Metronidazole (careful in working dogs for explosive detection)
Genetic epilepsy - which breeds and variants?
1) Lagotto Romagnolo - benign familial juvenile epilepsy (LGI2)
2) Rhodesian Ridgeback - juvenile myoclonic epilepsy with photosensitivity (DIRAS1)
ADAM23 gene - Belgian shepherd, schipperke, Finnish spitz, and beagle, Australian shepherd, Kromfohrländer, Labrador retriever, whippet, –> proposing ADAM23 as a common risk gene for epilepsy with low penetranc
- susp: Dutch partridge dogs (CCDC85A)
Where data are sufficient, they usually support an autosomal recessive or polygenic recessive inheritance (De Lahunta)
Describe postictal MRI changes in dogs
T1W hypointense, T2W/FLAIR hyperintense with no or minimal contrast enhancement, and no to minimal local mass effect.
Locations: pyriform lobes and cyngulate gyri, hyppocampus, less commonly in the thalamus and frontal/parietal lobes.
Mostly bilateral and symmetric.
*These lesions are usually transient and not visible on repeat imaging (weeks to months later) once seizure control is achieved. On microscopic examination, these lesions consist of edema, vascular proliferation, neuronal loss, reactive astrogliosis, and occasionally neuronal necrosis. Similar findings are reported in humans and are presumed to be related to the excitotoxic effect of accumulated glutamic acid, which leads to cytotoxic edema.
Which horse breed has a presumptive genetic epilepsy?
Arabian foals . onset 3-9 MO, seizures may spontaneously cease after a few weeks
Adult horses may have IE related to the estrous cycle when estrogen levels are increased.
On the basis of negative autopsies in adult horses with late-onset epilepsy, this species may have an idiopathic epilepsy that is not apparent until at least 5 years of age.
DeLahunta
Toxins able to cause seizures (most important ones)
Lead: paint, linoleum, tar paper, wallboard, and roofing materials.
Metaldehyde - snail bait,
Hexachlorophene soap, ethylene glycol antifreeze, chlorinated hydrocarbon and organophosphate insecticides, fluoroacetate (1080), rodenticide (particularly bromethalin), fungicides with mercury, arsenicals in insecticides, and phenol and cresol germicides, and 5-fluorouracil.
De Lahunta
CBC changes with lead poisoning (in a dog with seizures)
Nucleated red blood cells, basophilic stippling, and a low packed cell volume (PCV) (may be present)
De Lahunta
How can the bromide serum levels be decreased more quickly then by simply discontinuing the drug?
NaCl IV infusion
De Lahunta
Which ASM has the potential to cause megaoesophagus?
KBr
- develops in the first few months of initiating therapy. It resolves rapidly with discontinuation of potassium bromide.
De Lahunta
Two phases of sleep
1 slow-wave
2 REM (or paradoxical)
During slow-wave sleep, normal resting muscle tone exists. In paradoxical sleep, complete atonia of all skeletal muscles occurs, except those necessary for respiration. This state causes a flaccid paralysis. Sporadically, the extraocular muscles breakthrough this lower motor neuron (LMN) inhibition and contract, causing eye movements, which is the basis for also naming paradoxical sleep rapid eye movement sleep. This portion of the sleep cycle is when dreaming occurs. Occasionally, other muscle groups break through this inhibition and contract. This breaking through is what is observed in small animals when, during their sleep, they exhibit facial muscle twitches or sporadic movements of their digits.
During slow-wave sleep, a decrease occurs in the heart and respiratory rates. In paradoxical sleep, respirations are shallow, more rapid, and irregular. Normally in small animals, slow-wave sleep occurs in 10- to 15-minute intervals, with approximately 5 minutes of paradoxical sleep.
De Lahunta
Four components of Narcolepsy in humans
1) excessive daytime sleepines
2) cataplexy - collapse due to complete atonia of skeletal muscles - the most common sign we observe in animals
* shorter sleep latency (extra sign for animals which we can see)
3) hypnagogic hallucinations
4) sleep paralysis
-these 2 can only be appreciated in humans
De Lahunta
Which breeds have an inherited basis for narcolepsy and which gene is involved?
CANARC gene - chromosome 12
- autosomal recessive
doberman pinschers, Labrador retrievers, and dachshunds
(the gene codes for a hypocretine receptor found on neurons of the locus coeruleus and dorsal raphe nucleus)
De Lahunta
Two forms of narcolepsy
1) genetic (CANARC gene) - defect in the hypocretin receptors in dorsal raphe nucleus and locus coeruleus neurons
2) acquired - low hypocretin levels in CSF (immune mediated destruction of the neurons of ventrolateral hypothalamic nucleus?)
De Lahunta
Which drugs facilitate and which inhibit paradoxical sleep?
1) Physostigmine and arecoline facilitate
2) atropine, scopolamine, norepinephrine, serotonin inhibit it.
De Lahunta
Breeds of horses with an inherited form of narcolepsy
Shetland ponies, the American miniature horse, and probably the Suffolk draft horse
De Lahunta
DDs for cataplexy?
Syncope - rapid onset and recovery, same as cataplexy
Seizure - uncontrolled muscle movements (and cataplexy is atonic)
Neuromuscular disorders - not so abrupt and recovery not so quick
De Lahunta
Which drug can be used to provoke a cataplectic episode?
physostigmine at 0.05 to 0.1 mg/kg of body weight should not induce cataplexy in a normal dog but may provoke an episode in the patient at risk for such an episode
De Lahunta
Which drugs can be used to stop a cataplectic episode?
1) imipramine (Tofranil) IV at 0.5– 1.0 mg/kg of body weight, - antidepressant that inhibits the reuptake of norepinephrine and has anticholinergic actions.
2) IV atropine sulfate at 0.02–0.04 mg/kg of body weight may also interrupt the episodes.
De Lahunta
Drugs to treat narcolepsy
- Imipramine - norepinephrine reuptake inhibitor - has anticholinergic effects 0.5 mg/kg TID
- Selegeline - MAO inhibitor . increases the conc. of norepinehrine in CNS 0.5-1 mg/kg SID
- Methylphenidate (Ritalin) - stimulant only for excessive sleepiness
- Yohimbine - alpha-2 adrenergic antagnist - increases the release of norepinephrine
- Modafinil and Oxzbate in humans
De Lahunta
image from Dewey/Da Costa
Which gene variant is associated with congenital myotonia?
DNA mutation of the gene responsible for chloride channel 1 in the muscle membrane
CLCN1
This voltage-gated chloride channel 1 plays a role in the repolarization of the muscle cell membrane after contraction. When the function of this channel is deficient, muscle cell relaxation is delayed. No light microscopic lesions exist in the affected muscles of animals with inherited nondystrophic myotonia.
Breeds of animals with congential myotonia
Documented in:
- rats
- goats (pygmy)
- horses
- cats
- dogs
- buffaloes
- pigs
Dog breeds with CLCN1 variant:
Miniature Schnauzer
Jack Russell Terrier (common)
Australian Cattle dog
Labrador Retriever
American Bulldog
In addition to these breeds, has been described clinically in Cocker Spaniels and
Chow Chows (common)
Which electrolyte disturbance is connected to myotonia in horses?
Inherited hyperkalemic periodic paralysis
De Lahunta
Most likely diagnosis?
1YO Chow chow with muscle hypertrophy and stiff gait
Myotonia congenita
De Lahunta
Most likely diagnosis?
8 MO standardbreed with stiff gait
Myotonia congenita
De Lahunta
Causes of pseudomyotonia (complex repetative discharges)?
1) dystrophinopathy (retriver)
2) dietary deficiency of vitamin E/selen in farm animals
3) (Cushing’s myopathy - may be myotonia or pseudomyotonia)
4) Paradoxal pseudomyotonia of spaniels
- Myotonia is defined as a delayed muscle relaxation after muscle activation, usually preceded by a period of rest, and improving with continuous activity (warm-up phenomenon).
*In paradoxical myotonia, the delayed muscle relaxation occurs and worsens with repeated muscle activation (exercise), and improves with rest. - Pseudomyotonia is defined as delayed relaxation in muscle contraction after a voluntary movement, and is characterized by the absence of myotonic discharges on EMG.
De Lahunta
Most common disease associated with acquired myotonia?
Hyperadrenocorticism
persistent characteristic gait stiffness associated with significant muscle hypertrophy
(Can also cause pseudomyotonia)
Difference between true and pseudomyotonic discharges on EMG?
- complex repetitive discharges observed with pseudomyotonia (acquired myotonia with hyperadrenocorticism, or myotonia associated with dystrophinopathy) start and stop abruptly, without the waxing and waning that is seen in “true” myotonia.
Patomechanism of tetnospasmin?
interferes with the interneuron release of the inhibitory neurotransmitter glycine in the spinal cord ventral gray horn and γ-aminobutyric acid (GABA) in the brainstem motor nuclei.
The toxin gains access to motor neurons at their telodendrons at the neuromuscular junctions and binds to the axonal gangliosides, where it is transported to the spinal cord within a few hours. The toxin passes from the general somatic efferent neuronal cell bodies to the adjacent inhibitory neurons at their synaptic sites. There the toxin binds to and enters the interneuron, called a Renshaw cell. This toxin is a zinc endopeptidase that cleaves the cell membrane protein necessary for the release of the inhibitory neurotransmitter and therefore blocks the release of the inhibitory neurotransmitter, glycine or GABA. The toxin usually remains bound to the interneuron for 3 or more weeks. In most cases the toxin spreads rapidly within the central nervous system (CNS), or the toxin may circulate through the vascular system to neuromuscular junctions and thereby gain access to other areas of the CNS. Although this tetanospasmin may bind to other neurons, the major site is on the inhibitory interneurons that synapse on the alpha motor neurons that innervate the antigravity extensor muscles.
De Lahunta
Most likely Dx in this cow?
Tetanus
Note the retracted ears, taut lips, extended neck, and elevated tail.
De Lahunta
Difference between tetanus and tetany?
Tetanus - sustained contraction of muscles without relaxation that most commonly affects extensor (antigravity) muscles.
Tetany - sustained contraction of muscles, usually the extensors, which is variably intermittent and is related to varying degrees of relaxation of affected muscles.
De Lahunta
Causes of tetany
1) hypocalcaemia
2) strychnine intox
3) inherited congenital tetany in polled Hereford calves (aka inherited congenital bovine myoclonus) (Glra1 gene variant)
4) familial reflex myoclonus of Labrador retriever puppies
5) lavender Arabian foal syndrome (lethal) (MYO5A gene)
De Lahunta
Dysfunction of which nerves is seen in bovine spastic paresis (Elso heel)?
hyperactivity of the γ-efferent neurons that innervate the intrafusal muscle fibers in the neuromuscular spindles of the gastrocnemius muscle
Which drug can help diagnose constant repetitive myoclonus (wrongly termed chorea) with distemper infection?
Lidokain IV stops the myoclonus.
Oral procainamide can be used as chronic therapy.
De Lahunta
Difference between hypo-, dys-, and demyelination?
1) hypomyelination -animals have recognizable clinical signs at birth or when they are able to walk.
2) dysmyelination - animals usually show clinical signs after they are a few weeks or months of age and have exhibited normal neuromuscular activity.
3) demyelination - myelin is formed and maintained normally, and the animal is normal until affected by a disease process that causes the loss of myelin.
Name some toxins able to induce a whole body tremor
metaldehyde (snail bait), pyrethrins,
lead,
hexachlorophene,
chlorinated hydrocarbons, organophosphates,
and numerous mycotoxins (penitrem A from Penicillium)
Macadamia nuts
Common breeds for “head bobbing” (postural repetitive myoclonus)?
Doberman pinscher
English bulldog
Boxer
Dog breed with susp. inheretad basis for orthostatic tremor (postural repetitive myoclonus)
young adult Great Dane
Which molecule is degraded by tetanospasmin
Synaptobrevin (a vesicle-associated membrane protein) in the Renshaw intrneurons - the result is irreversibly impeded release of GABA (brain) and glycin (SC)
How fast does tetanospasmin travel retrogradely in the axons of motor neurons to reach the interneurons?
Once bound, the toxin becomes internalized by endocytosis and is carried along the axon in a retro grade fashion at a pace of 75 to 250 mm per day.
Clinical signs in horses with tetanus?
- Stiffness (most commonly) - horses are hesitant to lower their neck
- stilted gait
- retraction of lips, flaring of nostrils (risus sadonicus)
- trismus
- prolapse of nicticating membrane
- urine retention
- fecal and gas retention
DDs: rabies, strychnine intoxication,
exertional rhabdomyolysis, and myositis.
Which virus probably causes Theilers disease (fatal hepatitis)
Equine Parvovirus (EqPV-H)
Negative prognostic factors for horses with tetanus?
- recumbancy
- severe/terminal signs
- dysphagia
VCNA
Which are the most common botulinum neurotoxins?
A, B, and C
(There are 8 different BoNTs: A, B, Ca, Cb, D, E, F, and G)
Type C is important for Europe (A,B USA)
Three routes by which an equide can acquire botulism?
1) wound infection
2) ingestion of preformed toxin (food, soil, carrion)
3) from GIT (shaker foal syndrome)
Which proteins are targets for the botulinum toxin
Toxin type A and E - SNAP-25 (synaptobrevin associated protein)
Toxin type B,D,F,G - VAMP-2 (synaptobrevin)
Type C - syntaxin 1 and SNAP-25
*only in PNS - it can not cross BBB, prevention of release of acetylcholin
Which muscles have high requiements for acetylcholine and are therefore affected early in botulism?
tongue, eyelids, tail, and anal sphincter
Which cells are most susceptible to damage in hyperammonemia (PSS)?
astrocytes
In liver failure, muscle, kidney, and the rumen become important means of detoxifying intestinal ammonia, and astrocytes play a role in uptaking ammonia and forming glutamine, a strong osmolar molecule, to help protect neurons from ammonia toxicity. Astrocytes also play a role in taking up and metabolizing other proinflammatory and neuromodulating molecules
Which protein is central to the pathogenesis of rabies?
Glycoprotein G
it forms spikes (peplomers) on the virus lipid bilayer membrane that are required for receptor binding, internalization, invasion, and immune evasion.
What are Negri bodies?
Rhabdoviruses induce the formation of cytoplasmic inclusions (Negri bodies in lyssavirus) that are mini-factories containing all the machinery (N, P, M, G, L) and cellular proteins required for viral replication.
*round, eosinophillic, perikarion, 0.3-20 mcm
* mainly in the Purkinje cells, brainstem nuclei neurons, pyramidal cells of the hippocampus (Ammons horn), and sometimes SC
* only around 50% of animals develop Negri bodies
Name the prion diseases affecting humans and domestic animals
1) sheep and goats (scrapie),
2) cattle (bovine spongiform encephalopathy [BSE]),
3) cervidae (chronic wasting disease),
4) mink (transmissible mink encephalopathy),
5) cats (feline spongiform encephalopathy),
5) human beings (kuru, Creutzfeldt Jakob disease, and others)
Which TSE was found to cross species barriers?
BSE (bovine spongiform encephalopathy)
How to distinguish MG from polymyositis?
Predisposing factor for congenital sensorineural deafness in purebred kittens?
white kittens with 1 or 2 blue irises
Causes of and findings in BAER with animals with conductive deafness?
see image +
pseudo-conductive deafness (although also conductive deafness in a way)
- dirty ear canals
- stenotic ear canals
which genes are associated with sensorineural deafness in dogs and cats?
Dogs: recessive alleles of the piebald (s) gene or the dominant allele of the merle (M)gene
Cats: dominant allele of the white (W) gene
Classification of deafness in dogs?
Prevalence of epilepsy in general dog population?
estimated to be 0.6–0.75 % in the general dog population.
Epidemiological population prevalence studies in specific breeds with idiopathic epilepsy has been conducted in the Labrador retriever (3.1 %), Belgian shepherd (9.4 %) and petit Basset Griffon vendeen (8.9 %), and pedigree studies in the Boxer, Irish wolfhound, English Springer spaniel, Vizsla, Bernese mountain dog, Standard poodle, Belgian shepherd, Border collie, Australian shepherd and Border terrier among others, and these have provided evidence for inherited epilepsy
Most common seizure semiology in dogs?
Focal epileptic seizures evolving into generalized epileptic seizures
Most coman prodromal signs in dogs with epilepsy?
- hours or days of restlessness, anxiousness, appear as being irritated (e.g. with uncharacteristic aggression towards other pets), or
- attention-seeking behaviour which is known to the owner as a long-term marker of a forthcoming seizure episode.
Types of motor seizers in dogs as per consensus?
1) tonic (versive and dystonic),
2) myoclonic (clonic),
3) tonic-clonic,
4) atonic
5) automatism (oroalimentary, pedal)
Non-motor seizures as per consensus in dogs?
1) Aura (best not be used) - A ‘subjective’ ictal phenomenon that, in a given patient, may precede an observable seizure; if alone, constitutes a sensory seizure. This can result in behavioral changes such as fear, aggression, searching behaviour, attention, body sensation.
2) autonomic (cardiovascular, gastrointestinal, sudomotor, vasomotor and thermoregulatory functions. In companion animals, salivation, mydriasis, urination and/or defecation may commonly be observed.)
Difference between reactive and reflex epileptic seizures?
Provocative factor: Transient and sporadic endogenous or exogenous element capable of augmenting seizure incidence in the patient with chronic epilepsy and evoking seizures in susceptible non-epileptic individuals.
1) Reactive:
A reactive seizure is a seizure occurring as a natural response from the normal brain to a transient disturbance in function (metabolic or toxic in nature)—which is reversible when the cause or disturbance is rectified. A provoked seizure can be considered as being synonymous with a reactive seizure.
2) Reflex:
Objectively and consistently demonstrated to be evoked by a specific afferent stimulus or by activity of the patient. Afferent stimuli can be: elementary, i.e. unstructured (light flashes, startle, a monotone sound) or elaborate i.e. structured, (a symphony). Activity may be elementary, e.g. motor (a movement).
What are TODD’S (or bravias) phenomena?
Lateralising (TODD‘S (or bravais’)) phenomenon - Any unilateral postictal dysfunction relating to motor, somatosensory and/or integrative functions including visual, auditory or somatosensory.
vs.
Non-lateralising phenomenon (behavioural changes like fear, aggression, polyphagia etc.)
Most common causes of reactive seizures?
intoxications (39 %, 37/96 of dogs) and hypoglycaemia (32 %, 31/96 of dogs)
Hypocalcaemia was the most frequent electrolyte disorder causing reactive seizures (5%)
Which percentage of dogs with structural epilepsy have neurological signs?
- 47 % of dogs with lateralised structural cerebral lesions had asymmetrical neurological deficits and
- 55 % of dogs with symmetrical structural brain lesions had symmetrical neurological deficits identified on neurological examination
Which percentage of dogs with structural epilepsy have a normal inter-ictal exam?
23 % (34/146) of dogs with structural epilepsy had a normal neurological examination in the inter-ictal period.
Minimum data-base (MDB) for Tier I epilepsy as per consensus?
1) complete blood cell count (CBC),
2) serum biochemistry profile (sodium, potassium, chloride, calcium, phosphate, alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin, urea, creatinine, total protein, albumin, glucose, cholesterol, triglycerides, and fasting bile acids and/or ammonia).
3) Urinalysis includes specific gravity, protein, glucose, pH, and sediment cytology.
A family history of IE further supports the diagnosis.
When should a re-MRI be performed if abnormalities found are presumed to be seizure-associated? What about CSF?
after a 16 week seizure free interval (whenever possible)
If CSF abnormalities are present but the results of investigations for infectious disorders on CSF and serum are negative and brain MRI is unremarkable or shows post-ictal changes, then the CSF analysis should be repeated following a seizure free interval of at least 6 weeks.
*Consensus
Percentage of dogs with identified underlying CNS structural disease, whose first seizure occurred ≥7 years of age and had an unremarkable inter-ictal exam.
59%
Which percentage of dogs with SE as first manifestation of seizures have IE, SE or reactive seizures?
45.1 % had structural epilepsy,
31.4 % had reactive seizures and
23.5 % had IE
Recommendations to perform MRI/CSF in dogs with epilepsy (after exclusion of reactive seizures) based on the Consensus?
- age at epileptic seizure onset <6 months or >6 years
- interictal neurological abnormalities consistent with intracranial neurolocalisation
- status epilepticus or cluster seizure
- a previous presumptive diagnosis of IE and drug-resistance with a single AED titrated to the highest tolerable dose.
Dog breed least likely to achieve seizure remission?
Border collie
Factor associated with reduced survival time/poor response to therapy in Australian Shepherds and Border Collies (Consensus)
young age at sezure onset <2y
Which gene variant may be associated with DRE in Border Collies?
ABCB1-polymorphism( (T > G variant) was detected in a later Japanese study with a frequency of 9.8 % among a Japanese Border Collie population. In contrast to a known “loss of function” for the nt230 (del4) mutation, the T > G variation is hypothesised to have an ABCB1 drug transporter”gain of function” and therefore potentially might contribute to drug resistance.
*ABCB1, also known as multi-drug resistance protein 1 (MDRP1), is one of forty-nine putative members in the superfamily of human adenosine triphosphate (ATP)-binding cassette (ABC) transporters that encode transporter and channel proteins that function as efflux pumps.
Typical onset, remission and gene variant in benign jouvenile epilepsy of Lagotto Romagnolo?
mean onset - 6.3 weeks of age (with most puppies being affected by 1–2 month of age).
spontaneous seizure remission by 8 to 13 weeks of age
LGl2 gene variant
*the epileptic seizures manifest with episodic stiffness, generalised tremor and a predominantly preserved consciousness. Although this seizure semiology is a rather uncommon presentation for epileptic seizures, epileptiform EEG activity was detected in affected puppies. Puppies that were severely affected also suffered from interictal ataxia and hypermetria.
Which gene variant is associated with neonatal encephalopathy with seizures (NEWS) in the Standard Poodle?
ATF2
NEWS manifests immediately after birth with ataxia, tremors and generalised tonic-clonic seizures. As a rule, affected puppies die within the first two months of life
Which dog breed is associated with polymicrogyria?
Standard (and Miniature) Poodle
Affected dogs experience cortical blindness and other neurologic abnormalities including abnormal (hypermetria) gait and behavioural changes. Neurological signs predominantly start at a very young age (<4 months). MRI examination is consistent with multiple disorganized gyri, which especially may be seen on T2-weighted dorsal plane images. EEG-examination of 1 dog revealed epileptiform discharges, including both spike and spike and wave discharges with voltage maximum potentials over the parietal/occipital region, which supported the repetitive behaviour as focal seizures
4 criteria, as per IVETF to start ASM?
1) Interictal period of ≤ 6 months (i.e. 2 or more epileptic seizures within a 6 month period)
2) Status epilepticus or cluster seizures
3) The postictal signs are considered especially severe (e.g. aggression, blindness) or last longer than 24 hours
4) The epileptic seizure frequency and/or duration is increasing and/or seizure severity is deteriorating over 3 interictal periods
Factors associated with a poor ASM response in canine epilepsy?
- cluster seizures,
- male sex
Canine breeds with severe and less levere forms of epilepsy?
1) moderate to severe clinical course:
Australian Shepherds, Border Collies, Italian Spinoni, German Shepherds, Staffordshire and Bull Terriers
2) less severe form:
Collies (mainly rough coated), Labrador Retrievers, Belgian Shepherds
*IVETF Consensus
Which common human ASM is not used in dogs and why?
1) too short elimination half-life: phenytoin, carbamazepine, valproic acid, and ethosuximide
2) toxic in dogs: lamotrigine (the metabolite is cardiotoxic) and vigabatrin (associated with neurotoxicity and haemolytic anemia)
*IVETF consensus
Efficacy of PB in decreasing seizure frequency in dogs?
60−93 % of dogs with idiopathic epilepsy when plasma concentrations are maintained within the therapeutic range of 25−35 mg/l
85 % of dogs administered PB became seizure-free for 6 months compared with 52 % of dogs administered Bromide
*IVETF consensus
Pharmacokinetics of PB in dogs?
Bioavailability 90%.
Peak serum conc. 4-8 h after PO administration.
Half-life 37-73 h.
Plasma protein binding 45%.
Crosses placenta and is teratogenic.
Metabolised in liver, excreted 25% unchanged via urine.
Which drugs inhibit the cytochrome P450 and thus can cause PB toxicity?
cimetidine,
omeprazole,
chloramphenicol,
trimethoprim,
fluoroquinolones,
tetracyclines,
ketoconazole, fluconazole, itraconazole, fluoxetine,
felbamate
topiramate
Common, uncommon adverse-effects and idiosyncratic reactions with PB?
PB mechanism of action?
allosteric modulator of GABAa receptor
Phenobarbital acts as an allosteric modulator which extends the amount of time the chloride ion channel is open by interacting with GABAA receptor subunits. Through this action, phenobarbital increases the flow of chloride ions into the neuron which decreases the excitability of the post-synaptic neuron. Hyperpolarizing this post-synaptic membrane leads to a decrease in the general excitatory aspects of the post-synaptic neuron. By making it harder to depolarize the neuron, the threshold for the action potential of the post-synaptic neuron will be increased.[42]
Direct blockade of glutamatergic AMPA and kainate receptors are also believed to contribute to the hypnotic/anticonvulsant effect that is observed with phenobarbital
Mechanism of action for imepitoin?
partial agonist of the benzodiazepine site of the GABAa receptor
also dose-dependently blocks voltage-gated calcium channel
Common, uncommon adverse-effects and idiosyncratic reactions with imepitoin?
How do you calculate the dose of NaBr in comparison to KBr?
The sodium salt form (NaBr) contains more Br per gram of compound, therefore, the dose should be approximately 15 % less than that calculated for KBr
*consensus
Mechanism of action for bromide salts?
may affect neuronal chloride ion channels, causing hyperpolarization of neuronal membranes and raising the seizure threshold. By changing the chloride conductance in neuronal membranes, it may stabilize epileptic foci in the brain.
Pharmacokinetics of Br salts?
- bioavailability 46%
- elimination half-life 25-46 days
- ## not metabolised by the liver, excreted unchangen in the urine
which drugs may enhance KBr elimination by blocking KBr reabsorption through renal tubular chloride channels?
Loop diuretics
Adverse effects of KBr?
KBr loading protocols?
Oral loading can be performed by administering KBr at a dose of 625 mg/kg given over 48h and divided into eight or more doses.
A more gradual loading can be accomplished giving 125 mg/kg/day divided in three to four daily administrations for 5 consecutive days.
LEV mechanism of action?
- interaction with the synaptic vesicle protein 2A (SV2A) whereby it seems to modulate the release of neurotransmitters
Elimination half-life of LEV in dogs?
3-6 h
ASM with proven “honeymoon effect” for epilepsy in dogs?
LEV and zonisamide
Mechanism of action for zonisamide?
The exact mechanism of action is unknown, however, blockage of calcium channels, enhancement of GABA release, inhibition of glutamate release, and inhibition of voltage-gated sodium channels might contribute to its anticonvulsant properties
Factors associated with seizure remission or likelihood of achieving a ≥50 % reduction in seizure frequency on therapy?
Which breeds go least likely into remission or 50% reduction of seizure frequency?
- female sex
- neutered,
- no previous experience of cluster seizures
- an older age at onset of seizures
The breed least likely to go into remission or have an ≥50 % reduction in seizure frequency was the Border Collie (0 and 40 %, respectively), the German Shepherd (11 and 35 %, respectively) and Staffordshire Bull Terrier (0 and 57 %, respectively)
Which areas/cells of the brain are most affected by postictal changes?
grey matter of the forebrain
+
Purkinjne cells (laden with glutamatergic synapses)
*consensus
Youngest reported onset of MG?
6 Mo onwards
Lowrie et al 2020
Currently reported Congential myasthenic syndromes (CMSs) in dogs and cats including the affected neuromuscular compartment, the mechanism of failure of neuromuscular transmission, the affected protein, and the underlying mutated gene?
Recently CMSs have been characterized in both dogs and cats with specific mutations identified in the genes encoding:
1) the nicotinic epsilon subunit of the AChR (CHRNE)
2) choline acetyltransferase (CHAT)
3) the collagen-like tail subunit of the asymmetric acetylcholinesterase (COLQ)
Which receptors can be targeted in dogs and cats with MG?
nicotinic acetylcholine receptor (AChR) and
muscle specific kinase (MUSK) in dogs
in cats only AChR
Classification of MG in dogs and cats?
Focal MG is defined as weakness in ≥1 focal skeletal muscle group that does not involve the appendicular skeletal muscles. These focal skeletal muscle groups are the facial, esophageal, pharyngeal, and laryngeal skeletal muscles.
Generalized MG is defined as appendicular skeletal muscle weakness, which can range from mild to severe, with or without facial, esophageal, pharyngeal, or laryngeal skeletal muscle involvement.
Acute fulminant MG is defined as an acute, rapidly progressive and very severe form of generalized MG frequently but not necessarily causing respiratory failure and death.
Targeted protein in thymoma- and nonthymoma associated MG?
AChR
but
striational autoantibodies against titin and the ryanodine receptor also are reported in some dogs
Percentage of dogs with seronegative MG?
2% in the generalised MG
Gold standard of diagnosing MG?
measurement of AChR autoantibody concentration using radioimmunoassay
The incidence of a concurrent cranial mediastinal mass in dogs and cats with MG?
3.4% of dogs
52% of cats
Most frequent cause of death in patients with MG?
aspiration pneumonia with resp. failure
The 1-year mortality rate for the disease including all subgroups together is 40% to 60% in dogs and 15% in cats
Definitions of remission in MG?
Clinical remission is defined by the resolution of clinical signs of MG.
Immune remission is defined by the resolution of clinical signs in conjunction with discontinuation of treatment and normalization of serum AChR autoantibody concentration.
Percentage of dogs that go into remission, have a reponse or no improvement in ME?
ca 30% clinical remission
ca 40% clinical response or improvement
ca. 30% no clinical improvement
relapse only in 3% of dogs
Factors negatively associated with clinical remission in MG in dogs?
- older age
- regurgitation
- high initial AChR Ab concentration
*presence of endocrine disease may be a positive associated factor for remission
Positive prognostic facors in dogs with MG?
- Younger age,
- absence of regurgitation,
- the presence of comorbid endocrine disease, and
- lower initial concentration of AChR Ab
Percentage of dogs that have megaoesophagus in MG?
70-90% depending on study
Breeds of cats predisposed for acquired MG?
Abyssinians and related Somali breeds
The reported incidence of
megaoesophagus in diagnosed feline acquired myasthenia gravis?
37–50%
Classification of congential myasthenic syndromes in dogs and cats?
1) Presynaptic:
Defect in ACh synthesis -
ChAT (choline acetyltransferase) protein (CHAT gene)
Dogs: Old Danish Pointing dog
2) Synaptic:
AChE deficiency
COLQ protein and gene (COLQ)
Dogs: Labrador Retriever, Golden Retriever
Cats: Sphynx, Devon Rex
3) Postsynaptic
AChR deficiency
AChR ε subunit protein (CHRNE gene)
Dogs: Jack Russell Terrier, Heideterrier
What does the COLQ protein do?
collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) anchors acetylcholinesterase (AChE) to the basal lamina of the NMJ
What does the aplication of AChE inhibitors do to animals with different types of CMSs?
Presynaptic: no effect
Synaptic: worsens muscle weakness or has no effect for retrievers. In cats it may temporarily improve signs of weakness.
Postsynaptic: my shortly improve muscle weakness
Treatment possibilities for dogs/cats with synaptic CMSs?
Administration of albuterol, however, can result in a temporary improvement of clinical signs in the COLQ-associated CMS reported in Golden Retrievers. Similarly, COLQ-associated CMSs in humans respond positively to β2-adrenergic receptor agonists such as albuterol and ephedrine, which are thought to stabilize the NMJ and decrease dispersion of AChRs.
Acetylcholinesterase inhibitors or 3,4-DAP however are contraindicated in COLQ-associated CMSs in humans because they generally result in exacerbation of clinical signs
Which brain nuclei are most commonly grouped into the basal nuclei in the veterinary literature?
caudate nucleus, putamen, endopeduncular nucleus (EPN), globus pallidus(GP), claustrum, and amygdala
Direct pathway of the basal nuclei (consensus)?
dopaminergic innervation of the caudate/putamen from the SNc increases inhibition of the SNr (and EPN not shown) by activating D1R on GABAergic medium spiny neurons (MSN). This releases the thalamus from tonic inhibition of these nuclei.
Loss of this inhibition increases the excitatory feedback from the thalamus to the motor cortex and caudate/putamen, thus promoting movement.
Indirect pathway of the basal nuclei (consensus)?
Medium spiny neurons (MSN) inhibit GABAergic neurons in the globus pallidus (GP). This releases the subthalamic nucleus from tonic inhibition, increasing excitation of the SNr/EPN, and in turn inhibition of the thalamus. Decreased thalamic excitation of the motor cortex and caudate/putamen inhibits movement. Dopamine inhibits MSN in the indirect pathway through the D2R (c).
Thus dopamine promotes movement by increasing activity of the direct pathway (A) and decreasing activity in the indirect pathway (C)
How is dystonia explained on a physiological level?
Cocontraction of agonist and antagonist muscles with spread from the origin to extraneous muscles.
Electromyographic (EMG) recording during an episode would be needed to demonstrate this feature.
Definition: A sustained, slow, involuntary contraction of agonist and antagonist muscles of a body region producing abnormal postures and/or involuntary movement of portions of the body along a longitudinal axis. May appear as a twisted posture of the limbs, trunk, or neck
Tremor appearance in association with sleep/wake cycles?
Tremors should only be observed when awake and cease during sleep.
Which characteristic distinguishes tremors from other involuntary muscle contractions?
its rhythmical character
The keyword in identification is “rhythmicity,” that is, cycles of regular muscle contractions.
Tremors are involuntary, rhythmic oscillatory movements of a body part with symmetric velocity in both directions of movement (i.e.sinusoidal), around a joint axis
Classification of tremors as per consensus?
1) resting tremors - observed when muscles are not active (not reported in vet. med.)
2) action tremors - observed when the muscles are active/supporting body against gravity
a) postural/orthostatic - whilst standing (dissipates on activity or upon lying down) –> ORTHOSTATIC TREMOR, IDIOPATHIC HEAD TREMOR
b) kinetic - whilst moving –> CEREBELLAR DISEASE
Classification of peripheral nerve hyper-excitability as per consensus?
1) fasciculations,
2) myokymia,
3) neuromyotonia,
4) cramps,
5) tetany,
6) tetanus
Causes of peripheral nerve hyperexcitability?
can be caused by a wide variety of central and peripheral nervous system disorders,
but is particularly related to ion channel dysfunction
Causes include:
- hereditary channelopathies (VGKC mutation)
- immune-mediated channelopathies (VGKC Ab)
- paraneoplastic (VGKC Ab)
- polyneuropathies
- MND (VGKC dysfunction)
- neurodegenerative disease (VGKC dysfunction)
- metabolic disease (prolonged depolarisation)
- toxicities
- benign (stress, exercise)
Definition of muscle fasciculations as per consensus?
A brief spontaneous contraction resulting from the spontaneous activation of a small number of muscle fibers, often causing a flicker/vermicular movement under the skin.
Definition of myokymia as per consensus?
A focal or generalized continuous contraction of facial or limb myofibers, often exhibiting an undulation/vermicular movement of the skin overlying the affected muscle (ie, as if worms were crawling under the skin)
Causes of myokymia?
- benign/stress related
- brain disorders (myokymia of the head muscles)
- generalised myokymia/neuromyotonia in Jack Russell terriers
Difference between myokymia and neuromyotonia?
Electromyogram segregates myokymia from neuromyotonia due to the higher frequency discharges of neuromyotonia and their waning nature.
Myokymic discharges 5-150Hz
Neuromyotonic disharges 150-300 Hz
Definition of neuromyotonia?
A more severe form of myokymia, seen as persistent muscle stiffness and delayed muscle relaxation due to abnormal electrical discharges of motor nerves. Distinguished from myokymia in that it results in generalized muscle stiffness with delayed relaxation, often resulting in collapse. Both may occur simultaneously. Clinically results in noticeable muscle rippling. May be precipitated by stress and/or excitement
Definition of myotonia as per consensus?
- A disturbance in muscle relaxation after voluntary contraction or percussion.
- Is most noticeable after a period of rest, and improves with continued activity.
- Frequently results in noticeable hypertrophy of the affected muscles and may lead to diminished joint flexion when walking (ie, “stiffness” in the limbs)
Myokimia/neuromyotonia appearance in association with sleep/wake cycles?
persists during sleep and general anesthesia
(although can be blocked by neuromuscular blocking agents).
Definition of cramps as per consensus?
A sudden, severe, and involuntary muscle contraction or over-shortening that is generally temporary and benign. Can cause mild-to-excruciating pain, and immobility of the affected muscle(s). Onset is usually sudden, and resolves on its own over a period of several seconds, minutes, or hours.
Clinical classification of myoclonus as per consensus?
1) epileptic
- Lafora disease,
- Neuronal ceroid lipofuscinosis
- Feline audiogenic reflex seizures (FARS)
- Juvenile myoclonic epilepsy in Rhodesian Ridgebacks
2) non-epileptic
- Canine distemper virus
- Startle disease
- Hemifacial spasm
Classification of PxD as per consensus?
Inherited vs. acquired
Known genetic mutations for canine movement disorders?
PxD for which a known gene variant is noted?
- CKCS - BCAN (autosomal recessive)
- SCWT - PIGN (autosomal recessive)
- Shetland Sheepdog - PCK2 (dominant)
- Markiesje (Dutch Tulip Hound) - SOD1 (autosomal recessive)
- Weimaraner dogs - TNR (autosomal recessive)
Non-intentional head tremors in dogs can be associated with which intracranial lesion of which brain region?
Most commonly pituitary mass/lesions of the thalamic region
Which factors point to a structural cause in dogs with non-intention head tremor (as opposed to the idiopathic head tremor disease)?
1) presence of additional neurological signs
2) older age
may indicate an underlying structural cause for episodic (nonintentional) head tremor involving the mesencephalic aqueduct, third ventricle, interthalamic adhesion or some combination of these.
Name the glycoproteinoses in dogs/cats
Name the oligosaccharidoses in dogs/cats
Name the sphingolipidoses in dogs/cats
Name the mucopolysaccharidoses in dogs/cats
Name the proteinoses of dogs/cats
Most common MRI finding in dogs with hepatic encephalopathy?
Brain atrophy (forebrain + cerebellum)
- reduced volume of the brain (15/20), which showed variable degrees of forebrain atrophy alone (3/20) or in combination with cerebellar atrophy (12/16). The degrees of atrophy were mild in seven cases and moderate in the other 11 patients.
- T2W and FLAIR hyperintensity of the centrum semiovale and internal capsule (15/23)
*no cases had the T1W hyperintensities of lentiform nuclei noted
MRI findings in cats with hepatic encephalopathy?
Magnetic resonance imaging evaluation showed normal brain volume (2/3) or evidence of mild forebrain atrophy (1/3). Similar to dogs, changes of the white matter were most common at the centrum semiovale and corona radiata (2/3), with changes also visible at the internal capsule (1/3). The grey matter was also affected, including the cerebellar nuclei (2/3) as described in dogs, and also the medial longitudinal fasciculus and reticular formation (1/3)
Most prominent MRI feature in dogs with myelinolysis/osmotic demyelination syndrome?
T2W/FLAIR hyper-, T1W hypointensities of the thalamus and internal capsule (superior longiudinal fasciculus)
Most prominent MRI findings in dogs with thiamine deficiency?
Bilateral, symmetric intra-axial lesions were seen affecting the
- grey matter of the oculomotor nuclei (2/2),
- caudal colliculi (2/2),
- red nuclei (1/2),
- vestibular nuclei (1/2) and
- cerebellar nodulus (1/2).
These lesions were T2W and FLAIR hyperintense, T1W isointense to grey matter with mild contrast enhancement
Most prominent MRI findings in cats with thiamine deficiency?
Bilateral, symmetric intra-axial lesions were seen affecting the deep grey matter structures in all cases. The locations included:
- lateral geniculate nuclei (7/7),
- vestibular nuclei (6/7),
- facial nuclei (5/7),
- caudal colliculi (5/7),
- cerebellar nodulus (4/7),
- red nuclei (1/7),
- rostral colliculi (1/7) and
- periaqueductal grey matter (1/7).
Additional anatomical regions were the oculomotor nuclei (1/7), thalamic nuclei (1/7), subthalamus (1/7) and cerebellar nuclei (1/7).
All the intra-axial lesions were T2W and FLAIR hyperintense, T1W isointense to grey matter and some of them showed mild contrast enhancement (3/7)
Most prominent MRI feature of hypertensive encephalopathy in dogs?
bilateral and symmetric intra-axial lesions affecting the white matter of the forebrain
None of these changes were associated to mass effect and the brain volume was judged as normal. The lesions were homogeneous, ill-defined, hyperintense in T2W and FLAIR, isointense in T1W and without contrast enhancement. DWI and ADC map were available in two cases, showing no evidence of restricted diffusion, being hyperintense on both images
Most prominent MRI feature of hypertensive encephalopathy in cats?
More dramatic involvement of the white matter with a diffuse involvement of the corona radiata from the frontal to occipital lobes + grey matter of the thalamus in one cat + mass effect
MRI of exogenous intoxications - key points
Metro intox - normal brain volume, no white matter lesions, bil. symm. hyperint. of red, vestibular, and cerebellar nuclei
Cycas revoluta, ethylene glycol and bromethalin intoxication - increased forebrain/cerebellum volume, involvement of the white matter of forebrain/cerebellum
MRI characteristics of dogs and cats w/ NCL?
- severe atrophy of the forebrain and cerebellum (11/11)
- thinning of the cortical grey matter (11/11)
- T2W and FLAIR hyperintensity of the white matter resulting in a decreased grey matter/white matter definition (11/11)
- corpus calosum isointense to grey matter (6/11)
- diffuse pachymeningeal enhancement postcontr. (2/11)
MRI characteristics of dogs and cats w/ GM1 and GM2 gangliosidosis/fucosidosis?
- normal brain volume > mild forebrain/cerebellar atrophy
- diffuse T2W/FLAIR hyperintensities of the white matter (mostly internal capsule/corona radiata)
- loss of gre/white matter distinction
MRI characteristics of dogs/cats with L-2-hydroxyglutaric aciduria?
- increased forebrain/cerebellum volume (11/11)
- diffuse T2W/FLAIR hyperintensity of cortical grey matter
- bilateral symmetric focal intra-axial lesions affecting the grey matter at the following locations: thalamus (13/13), subthalamus (10/13), rostral colliculi (12/13), caudal colliculi (13/13), cerebellar nuclei (11/13), oculomotor (12/13), vestibular nuclei (12/13), red nuclei (9/13), lateral lemniscus (6/13), medial geniculate nuclei (5/13), lateral geniculate nuclei (2/13), globus pallidus and putamen (7/14).
- subcortical white matter hyperintensity (5/13)
MRI findings in Lafora disease?
- mild forbrain/cerebellar atrophy (6/11)
MRI findings in cerebellar cortical degeneration in dogs/cats?
- cerebellar atrophy with no other lesions
Radiographic-myelographic criteria to diagnose IVDE and differentiate from IVDP?
(1) thinning and deviation of the contrast columns,
(2) thinning of the contrast columns is mild to severe or contrast columns are discontinuous,
(3) thinning of the contrast columns is diffuse and beyond the boundaries of the affected disc,
(4) asymmetrical distribution of contrast column thinning cranial or caudal to the affected disc
in protrusion the deviation of the contrast column is usually mild and is centred over the affected disc spaces and distribution of contrast thinning is cranio-caudally symmetrical over the disc spaces.
Three different distinguishable groups of CT patterns in IVD herniation?
1) acute mineralised extrusion - mineralized nucleus is visible as heterogenous, hyperattenuating (mean 219 HU) extradural masses causing severe spinal cord compression
2) acute extrusion of nucleus pulpsosu with haemorrhage - material causing less compression, extending over multiple vertebral spaces, and that was only slightly distinguishable from the spinal cord (mean 59 HU)
3) chronic mineralised extrusion - extruded material extremely hyperattenuating (mean 745 HU) and more homogenous
Sensitivity of non-contrast CT vs CT myelography for diagnossi of IVDE?
81.8% for CT and 83.6% for myelography, though CT was better for chronically affected dogs
Which grading system is used in humans to grade IVD on sagittal T2W images ?
Pfirrmann system
it is based on a system for grading gross pathological changes in IVDs proposed by Thompson et al., which is the most commonly used criterion-referenced standard in human medicine.
The Pfirrmann system has been validated in dogs, showing good correlation with age and chondrodystrophic breeds, as well as the Thompson macroscopic grading scheme for disc degeneration
Extruded nucleus pulposus is typically identified as a ____________ (which signal intensity?) mass within the epidural space on T1W and T2W images in dogs with IVDE?
hypointense
MRI features of PMM?
- severe spinal cord swelling (more easily appreciated in the heavily T2 sequences HASTE/ myelo-MRI),
- diffuse parenchymal hyperintensity on T2W images over several spinal cord segments
- on transverse T2W images, the hyperintensity is centered in the gray matter.
*
dogs can develop PMM without the presence of spinal cord hyperintensity on MRI
MRI criteria for differentiating IVDP vs. IVDE?
- Midline instead of lateralized intervertebral disc herniation was associated with a diagnosis of IVDP
- Partial instead of complete loss of the hyperintense signal of the nucleus pulposus was associated with a diagnosis of IVDP
- The presence of a single intervertebral disc herniation instead of multiple intervertebral disc herniations was associated with IVDE
- Herniated material dispersed beyond the boundaries of the intervertebral disc space was associated with a diagnosis of IVDE.
Prognosis for acute TL-IVDE based on presenting grade of injury and treatment choice?
Outcomes (ambulation, continence) of dogs with ANNPE and FCE?
Overall percent of dogs achieving independent ambulation based on presenting injury severity
MRI characteristics of extra-axial masses
- broad-based meningeal contact,
- mass that forms an obtuse angle with the surface of the adjacent brain,
- may widen the subarachnoid space, and display a “dural tail sign” on post-contrast
MRI characteristics of intra-axial masses?
- mass forms an acute angle with the surface of the adjacent brain
- absence of adjacent meningeal enhancement.
- normal brain is typically evident between the lesion and the neurocranium.
- “claw sign,” defined as occurring when an expansile lesion within an organ creates
thinning of the surrounding parenchyma generating a “claw-like” appearance
Histiocytic sarcoma and meningioma share many MRI features.
Which features are helpful in differentiating the two?
Meningiomas more commonly had
- a broad based appearance toward the neurocranium,
- cyst-like changes,
- osseous changes such as sclerosis/thickening of the adjacent neurocranium, and
- perilesional and pachymeningeal enhancement compared to HS.
Histiocytic sarcoma tended to have
- more extensive edema and
- more often had combined perilesional and distant meningeal enhancement affecting both the pachymeninges and leptomeninges.
- HS may display T2w isointensity or hypointensity more commonly than meningiomas.
The T2w FLAIR mismatch signal is specific for which canine brain neoplasia?
oligodendroglioma (most commonly low grade)
The T2w FLAIR mismatch signal, described as lesions characterized by homogeneous T2w hyperintense signal that are T2w FLAIR hypointense (null signal) with a T2w FLAIR hyperintense peripheral rim, has been identified as an imaging marker for oligodendrogliomas in dogs. The T2w FLAIR mismatch signal is uncommon in dogs with gliomas with a low sensitivity of 16%; however, when it is present, it has a reported 100% specificity for the detection of oligodendrogliomas and is significantly
associated with non-enhancing low-grade oligodendrogliomas.
High-grade gliomas can infiltrate across the corpus callosum resulting in bihemispheric lesions that may have a symmetric, wing like appearance, termed _____________
“butterfly” glioma
Main imaging criterion for diagnosis of gliomatosis cerebri?
Signal abnormalities of the cerebral white and gray matter in at least 3 contiguous cerebral lobes with involvement of the thalamus and structures in the caudal fossa are suggestive of diffuse glioma with a gliomatosis cerebri growth pattern in dogs.
What is allodinia?
Pain provoked by a stimulus that does usually not cause pain
Most common clinical signs in L-2-hydroxyglutaric aciduria of Staffordshire Terriers?
Prognosis?
- Gait abnormalities (stif gait, kyphosis, wide base stance)
- Behavioural changes (dementia, seizure like episodes, staring into space, loss of training)
Prognosis: progressive disease, but dogs can live their normal life span
MRI changes in dogs with L-2-hydroxyglutaric aciduria?
Extensive, bilaterally symmetrical increased signal is present, particularly affecting the :
cerebral cortex,
cerebral white matter (white arrowheads),
thalamus (closed white arrow),
caudal colliculi (open white arrow),
dorsomedian tegmentum (open white arrowhead)
and the cerebellar nuclei (black arrow), including the dentate nucleus.
The central region of the internal capsule (small black arrowhead) and the corpus callosum retained the normal white-matter signal.
Negative prognostic factors in dogs with Nerve sheet tumours?
Compression of the brain and SC
Most common location to be affected by NST in dogs?
Brachial plexus
Among the cranial nerves: CN V
Gene variants associated with muscular dystrophies in dogs?
1) DMD - Dystrophin Deficient Muscular Dystrophy (x-linked): Golden + Lab ret., Rottweiler, Jack Russell Terrier, CKCS, Pembroke Welsh Corgi, Mini Poodle, Brittany Spaniel …
2) Limb girdle muscular dustrophy - SGCD and SGCA gene (autosomal recessive): Boston terrier and Miniature Dachshund
3) Congenital Muscular Dustrophy: COL6A1, COL6A3, LAMA2 and LARGE1 genes: Landseer Newfoundlender, Labrador retriever, Amstaff, Italian Greyhound, Staffordshire Bull Terrier, Labrador retriver
Prognosis for FIP cats treated with nucleoside analogues?
- Overall, 75–100% response; if survive first 48 hours, 80–90% survival
- CNS form carries a worse prognosis; dry form may have slightly lower response rate
Risk factors associated with developing the neuro form of distemper?
- Younger dogs
- Shih Tzu and Lhasa Apso
Most of the CDV-infected dogs showed multifocal (10/17) and associated extra-neural signs (16/17).
The most common neurological sign was motor deficit (13/17), and only one-third (6/17) showed myoclonia.
Prevalence, mortality, and lethality were 4,72%, 2,22%, and 47,05%, respectively.
True or false:
epileptic dogs receiving AEDs are statistically less active and have better sleep quality compared to age and breed matched controles?
True
BAER findings in cats with Niemann-Pick type C?
- significantly greater (p < 0.05) central conduction time at 16 and 24 wk of age compared with wild type cats
- significantly lower (p < 0.05) wave V/I amplitude ratio at 16 and 24 wk of age compared with WT cats
- Central conduction time was defined as the time between the first and the fifth peak. Wave V/I amplitude was determined by dividing the amplitude of the fifth wave by the amplitude of the first wave and multiplying by 100; amplitude was measured from peak to peak
Clinicopathological findings in cats with Niemann-Pick type C?
- increased activity of AST, ALT, AP
- decreased albumin
- increased cholesterol
- increased bilirubin
Gene variant and acumulated substance in Nieman-Pick type C?
NPC1 missense variant
Niemann-Pick type C (NP-C) disease is a neurovisceral lysosomal storage disease characterized biochemically by the endosomal/lysosomal accumulation of unesterified cholesterol, sphingomyelin, and other glycolipids, and clinically by hepatosplenomegaly, progressive neurologic dysfunction, and early death
Which material is accumulated in globid cell leukodystrophy (Krabbe’s disease)?
Deficiency of β-D-Galactocerebrosidase leads to acumulation of galactosylsphingosine (psychosine) within Schwann cells and oligodendrocytes
Typical hystology changes in globoid cell leukodystrophy?
- bilaterally symmetrical white matter demyelination and striking perivascular hypercellularity characterized by numerous plump globoid macrophages.
- The centrum semiovale, corona radiate, corpus callosum, optic tract, and cerebellar medullare are most severely affected.
- Peripheral subpial areas are the most commonly affected portion of the spinal cord.
- The intracytoplasmic material within macrophages is typically PAS positive, non-metachromatic, and non-sudanophilic.
- Leukocyte immunohistochemical markers such as CD18 or MAC1 can be used to confirm globoid cells are of macrophage/microglial origin
Source: Joint Pathology Center
Veterinary Pathology Services
Wednesday Slide Conference
2017-2018
Conference 3
September 6th, 2017
Known breeds and gene variants for globoid cell leukodystrophy?
galactosylceramidase (GALC) gene
- West Highland White
- Cairn Terriers
- Irish Setters
- mix breed dogs of Collie descent
Staging system of feline temporal lobe epileptic seizures?
Presence of which neural autoantibodies is associated with temporal lobe epilepsy in cats?
LGI-1 autoantibodies
MRI changes in feline hippocampal sclerosis and necrosis?
- increased signal of the hippocampus +/- piriform lobe on T2W and FLAIR
- swelling (necrosis) or shrinkageage (sclerosis) of the hippocampi
- Hippocampal asymmetry
- homogenous or heterogenous, mild to severe hippocampal contrast enhancement (h. necrosis)
Pathohistological changes in feline temporal lobe epilepsy?
- selective subtotal loss of hippocampal neurons together with astrogliosis.
- lesions predominantly localised in the CA3and CA4 segments in monosegmental types and within CA3 and CA4 in multisegmental distributed cases
- dentate gyrus pathology comprises blurring of the granule cell layer–molecular layer boundary, individual or clusters of ectopic granule cells, gaps of the granule cell layer and bilamination.
Fig. 4. Cat brain with hippocampal sclerosis. Segmental extensive loss of pyramidal neurons in the cornu ammonis (asterisks) together with astrogliosis, and proliferation of microglia (arrows) and capillary. Hematoxylin-Eosin. Bar = 160 µm.
Source: Pakozdy et al 2023 Temporal lobe epilepsuy in cats
Factors influencing mortality in “bottom hung window” syndrome?
- severity of neurological grade on admission, with the majority of cats having a neurological grade of 5 (paraplegia with loss of deep pain perception) at admission dying (11/31) rather than undergoing euthanasia on admission at the owner’s request (6/31).
- In the survivors’ group, loss of deep pain perception was not a negative prognostic factor for regaining motor function although it was associated with mortality.
Factors associated with mortality in “window entrapment syndrome”?
- Of the 70 cats that met the inclusion criteria, only seven (10%) died or were euthanased during hospitalisation.
- Cats lacking tail sensation, motor function and/or tonus were more likely to die
- cats with severe hypothermia or an absent femoral pulse were less likely to survive
Feline coronavirus (FCoV) is a DNA or RNA virus?
ubiquitous RNA virus present in many cat populations around the world
All coronavirus infections in cats cause FIP, true or false?
false
Coronaviral genomes possess a high level of genetic variation due to the error rate of RNA polymerase, leading to multiple mutations. Although FCoV infections can undergo a systemic phase within monocytes in healthy cats, mutations occurring in an individual cat are believed to allow a switch of cell tropism from enterocytes to monocytes to enable the subsequent development of highly pathogenic FIP-inducing FCoV
Typical signalment for FIP?
- pedigree cats
- younger than 2 yrs
- in some studies, males were more likely to develop FIP than females.
The FCoV is very resistant to desinfection, true or false?
false
Being an enveloped virus, FCoV is readily inactivated by most disinfectants, steam, and washing at 60 °C. It has been suggested it might preserve its infectivity for days to a few weeks, depending on environmental conditions and protection by faecal matter.
The FCoV is made of the following elements: a single-stranded (ss) RNA and the structural proteins; spike, envelope, membrane and nucleocapsid proteins.
Mutations in different genes, including the S gene, have been postulated to be associated with the switch to a more virulent FCoV pathotype. True or false?
true
The S protein is a particular focus of attention as it mediates entry into feline host cells and has both receptor-binding and fusion functions. Specific mutations in the S gene have been postulated to be associated with FIP-associated FCoV but the definitive genes and mutations involved in the FCoV virulence genetic shift are still unknown.
FCoV is divided into types ___ and _____, based on growth in vitro, genomic properties, and antigenicity
I and II
- Most laboratory research has focused on type II FCoV strains since they, unlike type I FCoV, can be readily propagated in vitro (facilitating experimental studies), despite most field infections being type I FCoV.
Two pathotypes of FCov?
feline enteric coronavirus (FECV), which mainly replicates in the enteric epithelial cells, and feline infectious peritonitis virus (FIPV),
Main route of transmission for FCoV?
Faeces are the main source of FCoV infection and most transmission is faecal-oral in nature.
Which percentage of FCoV cats usually develop FIP?
< 10%
FCoV is then found in the _________ (which part of the GIT?), which is the main site of viral replication alongside the _________.
colon
ileum
Cats resistant to FIP are known to have strong _________ immunity , which can be measured by high levels of the cytokine ____________ in the serum.
cell-mediated immunity (CMI)
interferon gamma (IFN-γ)
A study, which described the clinical features of FIP, documented fever in____% of FIP cases. Fever was shown to be more common in cats with ______ (which form of FIP?)
56%
effusion than in cats without effusion
FIP is a very common diagnosis in cats with pleural effusion, true or false?
FIP was only diagnosed in 9% of cats, while cardiac disease was the most common aetiology (35%), followed by neoplasia (31%), pyothorax (9%) and chylothorax (5%).
Cats with FIP were significantly younger than those with cardiac disease and neoplasia, and cats with cardiac disease had a significantly lower body temperature, higher serum alanine aminotransferase and alkaline phosphatase activity, and lower protein concentrations and nucleated cell counts in the effusion than cats with FIP
Which percentage of cats with FIP show neuro signs?
- up to 30%
- sometimes, cats present only with neuro signs
Most common neurological syndromes (neuro-localisations) in cats with neuro FIP?
In a study of 24 cats:
- 14/24 had multifocal CNS disease,
- 7/24 had central vestibular syndrome
- 3/24 had a T3-L3 myelopathy
Fever was less common in cats with neurological FIP compared to those without neurological signs, true or false?
true
Common neuro signs in FIP?
- ataxia (with varying degrees of tetra- or paraparesis),
- hyperaesthesia,
- nystagmus,
- seizures,
- behavioural and
- mental state changes,
- cranial nerve deficits (central vestibular disease)
Common CBC changes in FIP?
- lymphopenia,
- neutrophilia, sometimes with a left shift,
- mild-to-moderate normocytic, normochromic anaemia.
Common biochemistry changes in FIP?
- hyperglobulinaemia,
- hypoalbuminaemia
- a low albumin to globulin (A:G) ratio of less than 0.4 (an A:G ratio of greater than 0.8 makes FIP very unlikely).
- Increased bilirubin levels in the absence of haemolysis
- elevations of liver enzyme activity
- elevated α1-acid glycoprotein (AGP),
- elevated serum amyloid A
Which tests can be done on cavity effusions to help diagnose FIP?
- protein: highly proteinaceous, with a total protein concentration greater than 35 g/L consistent with an exudate,
- cell count: often low cell counts of less than 5 × 109/L cells, more consistent with a modified transudate; however, sometimes, cell counts rise to 20 × 109/L.
- Cytology: pyogranulomatous, with macrophages, non-degenerate neutrophils and few lymphocytes. Thick eosinophilic (pink-red) proteinaceous backgrounds on cytology slides are often described. If cytology reveals a septic neutrophilia (typically with degenerate neutrophils containing bacteria), neoplastic cells or a marked lymphocyte population, other diseases are more likely.
- The Rivalta’s test is a crude point-of-care assay to identify proteinaceous inflammatory exudates, which occur with FIP, but also septic peritonitis and lymphoma. If positive, effusion cytology can be helpful to discriminate between these causes. A negative Rivalta’s test, however, is more helpful to rule out FIP.
CSF changes in cats with FIP?
- elevated protein concentrations (of greater than 0.30 g/L [greater than 30 mg/dL] in cisternal samples, and greater than 0.46 g/L [greater than 46 mg/dL] in lumbar samples
** occasionally, marked elevations of protein occur (greater than 20 g/L [200 mg/dL]). - increased cell count (greater than 0.008 × 109/L [greater than 8 cells/µL] in either lumbar and/or cisternal samples; reference range less than or equal to 0.008 × 109/L [less than or equal to 8 cells/µL]);
** occasionally this pleocytosis is extremely marked in cats with FIP (cell counts of greater than 1 × 109/L [greater than 1000 cells/µL]). - pleocytosis is predominantly neutrophilic, mononuclear, mixed, or pyogranulomatous
- sometimes unremarkable CSF
Common MRI findings in cats with FIP?
- obstructive hydrocephalus,
- syringomyelia
- foramen magnum herniation and the
- marked contrast enhancement of the meninges, third ventricle, mesencephalic aqueduct and brainstem
(MRI may be normal in some cats)
Which histopathologic findings are consistent with FIP?
- Pyogranulomas on one or more serosal surfaces;
- Granulomas with or without necrotic areas;
- Lymphocytic and plasmacytic infiltrates in specific sites (e.g., band-like infiltrate in serosal surfaces, perivascular infiltrate in meninges and CNS);
- Granulomatous to necrotising vasculitis and fibrinous serositis.
Definitive diagnosis of FIP relies on ______________________________________?
consistent histopathological changes in affected tissues in addition to FCoV antigen immunostaining by IHC.
S-gene analysis after RT-PCR is very good in diagnosing FIP?
- Such techniques are only successful at determining the FCoV sequence present when high loads of FCoV RNA are present, so successful S-gene-mutation analysis at least suggests that the sample contained high levels of FCoV RNA, which is highly supportive of a diagnosis of FIP.
- However, research has shown great variability in results when detecting S-gene mutations using the different methods, making it difficult to rely on S-gene-mutation analysis as being confirmative for FIP, especially when the commercially available allelic discrimination assay is used.
Serum FCoV antibody tests, performed on blood, like: enzyme-linked immunosorbent assays (ELISA), indirect immunofluorescence antibody tests or rapid immunomigration tests, are very helpful in diagnosing FIP?
- A positive FCoV antibody test indicates that the cat has been infected with FCoV and has developed antibodies.
- Although cats with FIP tend to have higher FCoV antibody titres than cats without FIP, there is much overlap, so there is little value in an individual cat undergoing serum FCoV antibody testing.
- negative serum-FCoV antibody results cannot rule out FIP, as cats with confirmed FIP can be FCoV antibody-negative.
Which CSF FCoV antibody titre may be helpful in diagnosing FIP?
> 1:640
Horizontal transmission of FIP, via an FIP-associated FCoV strain, is a very likely occurrence, true or false?
false, horisontal transmission of the mutated FIP virus is unlikely
It is likely safe to take a cat that has been diagnosed with FIP back into a household with cats that have already been in contact with it, as these cats are likely to be already FCoV-infected following exposure to the same FCoV isolate that originally infected the FIP cat.
There is no need to keep cats with FIP in infectious disease isolation wards.
Disease progression in untreated FIP seems to be quicker in younger cats and cats with effusions than in older cats and cats without effusions, true or false?
true
Success rates for cats treated with the nucleoside analogue GS-441524 for FIP?
81% to 100%
How long does the usual treatment for FIP with nucleoside analogues last?
84 days
but shorter courses might be also effective.
Predictors of survival with nucleoside analogues in FIP?
- a good appetite and/or activity level,
- a higher temperature,
- a lower bilirubin concentration and
- fast normalisation of α1-acid glycoprotein (AGP)
- weight gain
A 5 YO mix-breed dog is presented to you with generalised neuromuscular signs. Electromyography identified spontaneous electric activity with positive sharp waves and fibrillation potentials were detected in the pelvic limb muscles and one muscle was biopsied.
What is shown in the image?
What is the most likely diagnosis?
Which further histologic diagnostics could you perform to confirm?
Longitudinal section of skeletal muscle. Within the sarcolemma of 1 myofiber there is a strongly basophilic parasitic cyst of several μm in length containing numerous bradyzoites (arrows).
Further test:
- Immunohistochemistry
- In situ hybridization
Serology is a very reliable method for diagnosing canine neosporosis, true or false?
false
(see paper)
