Lit Neuromuscular, MSK Flashcards
- What was the incidence of persistent fontanelles (PF) in Chihuhahuas?
- What are the predilection sites for PFs?
- Was there an association between PFs and chiari-like malformation/ syringomyelia-related clinical signs?
- PFs were associated with which individual characteristics and CNS structural abnormalities (name 4)?
Kiviranta JVIM 2021 (Parts I & II)
1. 92% with >/=1 PF.
2. Dorsal (48%), lateral (14%), caudal (37%) cranial surfaces.
3. Chihuahuas with CM/SM-related clinical signs have more numerous & larger PFs.
4. Small size, SM, ventriculomegaly, craniocervical junction overcrowding.
- Tumor type and/or grade of canine gliomas were strongly associated between clin path findings and survival. (T/F)
- Which MRI characteristics were found to be useful in:
a) refining diagnosis of tumor type & grade?
b) predicting shorter survival?
José-López JVIM 2021
1. False - no association identified.
2. a) Oligodendrogliomas associated with smooth margins & T1W hypointensity (vs astrocytomas & undefined gliomas), and more commonly in contact with ventricles (vs astrocytomas). Tumor spread to neighbouring brain structures was associated with high-grade glioma.
2. b) Irregular/poorly defined margins, T2W heterogeneous signal, drop metastases (seizures = lower risk factor)
What is the diagnostic utility of arterial spin labelling (ASL) in dogs & cats undergoing brain MRI?
Hoffmann JVIM 2021
Non-invasive technique that allows quantification of cerebral blood flow (CBF), can be useful to characterise various brain diseases.
What was the major adverse effect noted in dogs undergoing implantable vagus nerve stimulation (VNS) for treatment of epilepsy, and what is the mechanism behind this?
Harcourt-Brown JVIM 2021
Coughing which is generally well tolerated, esp if current is increased slowly & other stimulation parameters are adapted for effect.
Vagus nerve contains large efferent myelinated A fibers & small, unmyelinated C fibers –> fibre depolarisation causes adverse effects (dysphonia, dysphagia, cough, dyspnea, paresthesia, headache, pain)
List the dog breeds affected by hereditary sensory and autonomic neuropathies (HSANs), and the associated genetic variants.
Gutierrez-Quintana JVIM 2021
3 variants identified to date.
1. Inversion in RETREG1 (reticulophagy regulator 1) - encodes Golgi protein. Border Collies & BC crosses.
2. Point variant in GDNF gene - encodes glial cell-derived neurotrophic
factor. Pointer, English Springer Spaniel & French Spaniel.
3. RETREG1 - family of mixed breed dogs (all homozygotes). CSx severe acral
mutilation & progressive HL gait abnormalities.
In dogs with acquired MG, what was the:
a) clinical remission (CR) rate
b) immunological remission (IR) rate
c) factors negatively correlated with CR
d) factors positively correlated with CR
Forgash JVIM 2021
a) 31% (no CSx 4wks after stopping tx)
b) 59% (all IR dogs also achieved CR)
c) older dogs, regurgitation at presentation, high initial [AChR Ab]
d) Younger dogs, dogs with co-morbid endocrine dz
- What is the causal gene mutation identified in Golden Retrievers with congenital myasthenia gravis?
- Gene mutations in other dog breeds & modes of inheritance?
Differences in clinical presentation between congenital vs acquired MG?
Tsai JVIM 2020
1. Point mutation in COLQ gene that predicts an AA substitution (G294R). COLQ encodes the collagenous tail of AChE (enzyme responsible for termination of skeletal muscle contraction by clearing ACh at the NMJ)
- Danish Pointers - missense mutation in the gene encoding choline acetyltransferase
Labs - non-synonymous mutation in COLQ gene (encoding the collagen-like tail of the asymmetric acetylcholinesterase)
JRTs - deletion & non-synonymous mutation in the CHRNE gene (encodes the epsilon subunit of the nicotinic ACh receptor)
Congenital MG also reported in Smooth fox terriers & Eng Springer Spaniels (mutations not yet described) - Congenital MG - megaO is not a common clinical feature. CSx usually begin at weaning with progressive muscle weakness that is exacerbated by exercise.
In cats with acquired MG without a cranial mediastinal mass (CMM), what were the most consistent clinical abnormalities?
What was the clinical progression and long term prognosis of acquired MG w/o CMM in cats?
Mignan JVIM 2020
1) Skeletal muscle weakness. 2) Fatigability induced or exacerbated by the wheelbarrow exercise stress test.
Frequently achieve immune remission (within 6mths of diagnosis); can be spontaneous. Excellent long-term outcome - so impt to differentiate from cats with CMM.
What is serum high-mobility group box 1 (HMGB1) an indicator of in dogs?
Rank the serum [HMGB1]s in the following groups of dogs (from highest to lowest) and approximate [ ].
- Epilepsy course <3mths
- Healthy dogs
- Epileptic dogs
- Epilepsy course >3mths
Mediator of neuroinflammation.
- Epilepsy course >3mths (0.87ng/mL)
- Epileptic dogs (0.41ng/mL)
- Epilepsy <3mths (0.26ng/mL)
- Healthy dogs (0.12ng/mL)
No sig diff between dogs with non-epileptic brain dz & healthy dogs. Potentially useful biomarker of epilepsy.
What proportion of dogs
a) Developed post-encephalitic epilepsy (PEE) after MUO?
b) Developed drug-resistant epilepsy?
c) Clinical features (list 2) & d) risk factors (list 2) for PEE development after MUO in dogs?
Kaczmarska JVIM 2020
a) 23%
b) 21%
c) Clinical features - younger, significant shorter survival times
d) Risk factors - presence of acute symptomatic seizures (ASS; OR = 4.76) & MRI hippocampal lesions.
What proportion of dogs had effective seizure control with midazolam CRI:
- Dogs with cluster seizures (CS)
- Dogs with status epilepticus (SE)
- Overall (includes above + structural/reactive/idiopathic epilepsy)
Duration taken to achieve seizure control with midazolam CRI?
What was the incidence & type of adverse effects observed?
Bray JVIM 2020
CS - 81%
SE - 67%
Overall - 77.4%
~25hrs
22.6% AE, all mild (sedation, V+ or D+, hyperexcitability, ataxia, polyphagia)
Describe the following associated with seizures triggered by eating (STE) in dogs:
- Clinical feature
- Predominant seizure type
- Most common breed identified
- Associated with structural disease in which regions of the brain
Brocal JVIM 2020
- >50% of seizures related to eating
- Focal seizures becoming generalised
- Retrievers (4/10)
- Parietal, temporal, and frontal cortex (perisylvian region)
Repetitive transcranial magnetic stimulation (rTMS) to treat dogs drug-resistant IE:
- Define technique?
- Effect on seizure frequency?
- Duration of effect?
Charalambous JVIM 2020
- Non-invasive neurostimulation technique. May have potential long-lasting neuromodulatory effects on the brain - disrupts networks related to cortical hyperexcitability.
- Significantly reduced Monthly seizure frequency (MSF) & monthly seizure day frequency (MSDF)
- Overall effect of rTMS lasted 4 months (proportion of MSF post-TMS to pre-TMS <1).
- What was the causal gene & mode of inheritance identified in Mini Schnauzers with demyelinating polyneuropathy?
- Describe
a) Presenting signs
b) Age of disease onset & clinical presentation
c) Treatment strategies
d) Disease progression & prognosis
Mariné JVIM 2020
1. MTRM13/SBF2, autosomal recessive.
- a) Hallmark CSx - regurgitation + megaO & aphonic bark. +/- obvious neuromuscular weakness despite EMG evidence of appendicular DMP.
b) Age of onset = 3-18mths, clinical presentation = 4-96 mths
c) Preventive feeding measures & symptomatic tx to control aspiration pneumonia (meds, elevated feeding).
d) Disease tends to remain stable long-term - occ asp pneumonia (rarely cause of death). Overall good px with medical management.
Novel motor polyneuropathy in Siberian cats:
- Probable mode of inheritance
- Presenting signs
- Prognosis
Crawford JVIM 2020
a) Autosomal recessive
b) CSx – progressive or waxing/waning neuromuscular weakness (100%), normal sensory function (100%), variably decreased withdrawal reflexes (75%).
c) Good overall. Episodes self-limiting (usually within 1-4wks), recurrence (1 or more episodes) common but full recovery typical.
What is the prevalence of seizures in:
- Dogs & cats with idiopathic internal hydrocephalus
- Post-ventriculoperitoneal shunting for internal hydrocephalus?
Farke JVIM 2020
1.7%
None observed in study population (98 dogs, 23 cats)
Canine mucopolysaccharidosis type I (MPS-I) - describe:
a) Pathogenesis
b) Causal gene
c) Clinical presentation
d) 1 drug which may be useful in managing this disease.
Faller JVIM 2020
a) Lysosomal storage disorder. Caused by α-L-iduronidase enzyme deficiency –> accumulation of undegraded dermatan and heparan sulfates in cells –> secondary multiorgan dysfunction.
b) IDUA gene
c) Variable; dysmorphic appearance, MSK, ocular and cardiac defects. Can survive to adulthood.
d) Pentosan polyphosphate - improved CSx until euthanasia at 4.5yrs.
Prevalence of post-ictal MRI changes in dogs?
These changes were most commonly associated with:
- Which CNS regions?
- Which seizure types?
- Seizure frequency
- What timing of MRI wrt last seizure activity
Maeso JAVMA 2021
~12%
Locations - piriform lobe, hippocampus, temporal neocortex, cingulate gyrus.
Idiopathic > structural epilepsy (but can occur with both)
Cluster seizures or status epilepticus (vs self-limiting seizures)
Shorter time between MRI & last seizure
Define myoclonus & its classifications. What gene mutation is this associated with in dogs?
Lowrie JVIM 2017 (Review)
Sudden brief, involuntary muscle jerk. Epileptic vs non-epileptic in origin.
CLCN1 (skeletal muscle voltage-gated chloride) mutation
Non-epileptic myoclonic activity can occur with which infection in dogs? Pathogenesis? How does this present clinically?
Lowrie JVIM 2017 (Review)
Canine distemper virus.
Constant repetitive myoclonus occurs due to focal lesions causing pathological changes to the LMN of the spinal cord & cranial nerve nuclei - results in pacemaker - rhythmic muscle contractions.
Usually affects 1+ limb +/- facial muscle twitches;
What signalment is typical for cats affected by feline audiogenic reflex seizures (FARS)?
Clinical manifestation?
Prognosis?
What drug is effective (or ineffective) in the treatment of FARS?
Lowrie JFMS 2017 & 2018
Older cats (median 15yo at onset).
Birmans overrepresented (31%).
Seizures mostly triggered by high-frequency sounds, up to 20% spontaneous.
Generally non-progressive, but owner-perceived declining QOL with seizures >2yrs (not jumping, HL weakness, weight loss, less responsive).
Levetiracetam effective (decreased myoclonic seizure frequency by
>50%), whereas phenobarbital had minimal effect.
List some conditions associated with progressive myoclonic epilepsy (PME) in cats & dogs.
Lowrie JVIM 2017 (Review)
- Part of a degenerative encephalopathy.
a) Lafora disease (dogs) - usually occur in response to auditory & visual stimuli. Sudden muscular twitches ranging from jerky head mvts to generalized muscle fasciculations.
b) Neuronal ceroid lipofuscinosis (NCL) i.e. lysosomal storage disorder (dogs). - Unidentified aetiology (feline audiogenic reflex seizures)
What is Niemann-Pick type C disease NPC) that has been described in a cat? Mode of inheritance & causal mutation? Clinical manifesations?
Mauler JVIM 2017
Autosomal recessive. Neurovisceral lysosomal storage disorder - results in defective intracellular transport of cholesterol.
Missense mutation in NPC1 gene.
Neuro signs - cerebellar & vestibular signs as early as 6wks old. Progressive ataxia impairing ambulation - typically euthanised by 6mths.
What % of dogs/cats with supratentorial herniation had no direct clinical signs of herniation? What did the presence of a transtentorial line to the rostroventral aspect of the cerebellum (TTX) on MRI indicate?
Lewis JVIM 2016
75%
More severe caudal transtentorial herniation, worst 24hr survival.
What is a minimally invasive method of detecting high ICP in dogs?
Sasaoka JVIM 2018
Transcranial doppler ultrasound. Increased ratio of systolic to diastolic mean velocity of the basilar artery was associated with MRI findings of increased ICP.
What was the agreement between stereotactic brain biopsy vs traditional surgical resection or necropsy to diagnose intracranial neoplasia in dogs?
Kani JVIM 2019
High agreement for tumor type (kappa = 0.95), of which 100% concordance for meningiomas.
But grade agreement for gliomas was only k = 0.47, where SBB underrepresented glioma grade.
SBB had 81% diagnostic accuracy, worst with smaller tumors & fewer samples obtained.
(2 papers)
Apart from chiari malformation/syringomyelia, what other structural difference can CKCS dogs have in their spinal cords? What clinical implications does this difference have?
Sparks JVIM 2019
Spinal cord in CKCS terminates more caudally at sacrum (vs L7 in controls). Dural sac also terminates more caudally (associated with subsequent T-L syringomyelia).
Sparks JVIM 2021
Found that painful CKCS without SM have decreased distance between the SC termination
& dural sac, suggesting a shorter filum terminale length (band of fibrovascular and neuronal tissue). More caudal SC termination is associated with development of lumbar SM.
(2 papers)
What were the most common signs reported by owners of CKCS with/without SM based on a questionnaire?
What are some signs seen more commonly in CKCS with large syrinxes, vs dogs with chiari-like malformation (CM) that may not have synrinxes or have smaller ones?
Sparks JVIM 2018
Most common CSx = crying out when lifted.
Owner-reported findings were not significantly associated with presence or severity of SM, or neuro exam findings. Owner-reported lateralization of signs was significantly associated with SM lateralization.
Rusbridge JVIM 2019
* Phantom scratching (ipsilateral), scoliosis leading to torticollis if dorsal horn of SC is involved (ipsilateral shoulder deviation + contralateral head tilt), sensory & motor signs (weakness & postural deficits) only seen in dogs with wide syrinxes 4mm+.
* Vocalisation, spinal pain & other signs of pain (reduced activity/ jumping ability, touch aversion, altered emotional state, sleep disturbance) could be seen in even dogs without syrinxes.
(2 papers)
In a longitudinal study, did craniocervical junction (CCJ) anomalies in CKCS predict future development of syringomyelia? Where there differences in medical vs surgical treatment in determining clinical progression?
In what other breed are SM & CCJ abnormalities overrepresented, and were there any distinct features from those recognized in CKCS?
Cerda-Gonzalez JVIM 2016
No, not in this cohort. Study also looked at atlantooccipital overlapping but concluded larger studies needed to assess impact.
32% of asymptomatic dogs developed CSx at re-evaluation within 71mths.
No.
Kiviranta JVIM 2017
Chihuahuas.
CM present in 100% & SM present in 38% of study population.
Similarly dogs w/o syrinxes developed CM/SM-related signs, likely due to CCJ abnormalities.
What is mechanical testing potentially useful for when evaluated in CKCS with/ without craniocervical pain?
Sparks JVIM 2018
Mechanical sensitivity was not associated with presence of syringomyelia in this study, but did related to the presence of pain & CSx in CKCS - so may be useful to assess sensory abnormalities.
(2 papers)
What are the most common complications post ventriculoperitoneal shunt placement in dogs and cats with internal hydrocephalus respectively? When were these complications most likely to occur?
Post VPS placement, what was the association between decreased ventricular volume & clinical status?
Gradner JVIM 2019
Dogs - shunt obstruction (10%), pain (5.5%), shunt infection (4.1%), disconnection (4.1%), excessive shunting (2.7%), kinking (1.6%).
Cats - shunt coiling (15%), kinking (7.7%), obstruction (7.7%).
Most common in 1st 6 months post-placement.
Schmidt JVIM 2019
The extent of decrease in ventricular volume & increase in brain parenchyma after VPS are associated with improvement in CSx (resolution of ataxia & obtundation).
When is ventriculoperitoneal shunting considered an effective palliative option in dogs?
Orlandi JVIM 2020
Dogs with obstructive (hypertensive) hydrocephalus caused by tumors located within the third ventricle. VP shunting of the most dilated lateral ventricule resulted in rapid resolution of intracranial hypertension, and excellent clinical improvement post-op. Some dogs required 2nd VPS in the contralateral lateral ventricle.
Nova Scotia Duck Tolling retrievers can get what sort of brain disease associated with rapid eye movement (REM) sleep behaviour?
Barker JVIM 2016
Degenerative encephalopathy, autosomal recessive. Gray matter degeneration (necrosis/malacia) affecting the caudate nuclei & brainstem/spinal cord axons.
CSx start between 2mths-5yrs & are progressive. Px guarded, minimally responsive to tx.
In what canine breed has neuronal vacuolation and spinocerebellar degeneration (NVSD) been identified as a hereditary condition? What is the causal gene mutation?
What similar condition has been identified and in what 2 breeds?
Mhlanga-Mutangadura JVIM 2016
Rottweilers.
Homozygotes for RAB3GAP1 allele (asymptomatic heterozygous carriers identified).
Ataxia & weakness most common CSx.
**Polyneuropathy with ocular abnormalities & neuronal vacuolation (POANV). **
* Black Russian Terriers. Mutations in RAB3GAP1 gene which codes for a protein involved in membrane trafficking. Present with juvenile onset laryngeal paralysis & polyneuropathy.
* Alaskan Huskies - SINE insertion in RAB3GAP1 gene.
Disruption of membrane trafficking could lead to neuronal vacuolation seen in NVSD & other spongiform encephalopathies.
In a UK dog population, what breed was strongly predisposed to vestibular disease? What was the clinical response rate & median time to see improvement?
What is the proposed clinical benefit of propentofylline in dogs with vestibular disease?
Maria Radulescu JVIM 2020
French Bulldogs, Bulldogs, King Charles Spaniels, CKCS, Springer Spaniels.
41.8% dogs improved after ~4 days.
Propentofylline may speed up the brain’s ability to compensate after unilateral vestibular damage (tx course 1mth+)
What gene region was found to be associated with hereditary ataxia in Scottish terriers?
Urkasemsin JVIM 2017
CFA X
Mode of inheritance not yet identified.
What are the features of paroxysmal dyskinesia in Border terriers?
Stassen JVIM 2017
Dystonia, muscle fasciculations & falling over.
67% responded to AED, 100% response to hypoallergenic gluten-free diet when trialled.
Likely complex mode of inheritance, specific gene mutation not detected in this study.
(2 papers)
What is Lafora disease? What breeds can be affected? What are the CSx?
What brain metabolite deranagements were identified in a dog with Lafora disease using brain proton magnetic resonance spectroscopy?
Flegel JVIM 2021
Lysosomal storage disease. Lafora protein absent, leading to branched precipitous glycogen.
Beagles (also Basset Hounds, Wire-haired Dachs).
NHLRC1 (Malin) gene mutation.
Autosomal recessive.
CSx: Myoclonus, seizures, behavioural changes (increased photosensitivity, staring into space, reduced stress resistance, increased noise sensitivity & separation anxiety), mental decline.
- Also common: coordination deficits, impaired vision & hearing (develop later).
Usually a normal life span, onset of CSx in middle aged (8yo).
Alisauskaite JVIM 2020
Decreased amounts of N-acetyl-aspartate (NAA) & glutamate-glutamine complex; increased
total choline & phosphoethanolamine
What is the most common cause of unilateral MM atrophy in dogs?
What is the MST?
What was a negative prognostic indicator?
Milodowski JVIM 2019
Trigeminal NST in 47.6%. Other mass lesions accounted for 20.6%. Idiopathic 28% (no MRI lesions).
MST 5mths
Dogs with mass lesions more likely euthanised or had neuro deterioration.
Name a dog breed to have a described juvenile degenerative polyneuropathy associated with laryngeal paralysis & megaO. What were the treatments administered & clinical response?
What hereditary adult onset neuropathy has been described in this breed?
Vandenberghe JVIM 2018
American staffies. Autosomal recessive.
Generalised sensory + motor nerve involvement.
Lar par common (71%; 10/14 dogs), megaesophagus (7%; 1/14 dogs).
Surgery for larpar improved QOL. Slowly progressive disease in most dogs; post-op lifespan was then similar to normal dogs apart from locomotor disturbances.
Adult onset: cerebellar degeneration secondary to ceroid lipofuscinosis.
What population variables (sex/weight/breed) were associated with risk of seizures in a UK prevalence study?
Erlen JVIM 2018
Males, BW 40kg+, Labradors & Pugs (Boxers, Basset Hounds, Border Terrier, Border Collies)
(2 papers)
What factors can predict in-hospital seizures for dogs presented for seizure evaluation?
What additional seizure-precipitating factors were identified in dogs with IE?
Kwiatkowska JVIM 2018
50% of dogs seized in this paper, within mean 7hrs. IE dogs had the highest seizure recurrence rate (53%).
Predictive factors:
- All dogs (IE + structural + reactive epilepsy): clusters/SE in the 72hrs before presentation & abnormal neurological exam.
- IE dogs: post-ictal prosencephalic signs also predictive
Prosencephalic signs: mentation changes, visual deficits.
Forsgård JVIM 2019
Prevalence of seizure-precipitating factors = 74% in this study.
Stressful situations, sleep deprivation, weather & hormonal factors.
In dogs with focal seizures, no. of precipitating factors was 1.9x higher vs dogs with generalized seizures.
What was the impact of of oral cannabidiol (CBD) in conjunction with AEDs on seizure control in a placebo controlled trial in dogs?
McGrath JAVMA 2019
CBD 2.5mg/kg PO BID x12wks.
Reduction in seizure frequency by 33% (plasma [CBD] correlated with reduction in seizure freq). But no difference in response vs control groups (defined as 50+% reduction in seizures) - possible that higher dose may benefit.
Tx dogs had increased ALKP activity.
What was the impact of a MCT-enriched diet supplementation on seizure control in dogs with idiopathic epilepsy?
Berk JVIM 2020
Included dogs with 3+ seizure in 3 months.
9% ME-based amt of MCT.
Significantly reduced seizure frequency & seizure-day frequency.
Variable improvements (2/28 seizure-free, 3/28 50+% reduction, 12/28 <50% reduction, 11/28 no change).
Study also noted MCT supp improved tolerability of AED (less ataxia). MCT oil & metabolites may affect phenobarbitone absorption & excretion rates due to common metabolism by cytochrome p450 enzymes»_space; sig lower serum [ ] though clinically did not manifest as more seizures.
What impact do AEDs have on activity levels & sleep scores in dogs with IE?
Barry JVIM 2021
IE dogs receiving AEDs have 18% lower baseline activity; greatest decrease with phenobarb + KBr combo (28%). No difference in sleep scores.
What were distinct clinical characteristics associated with focal epilepsy in a litter of Boerboel dogs?
Stassen JVIM 2019
Paroxysmal fear behaviours.
All dogs also had autonomic or motor signs.
Histo - moderate #s of single large vacuoles in the perikaryon of neurons throughout the brain (specifically deep cerebral cortex).
