Neuromuscular, MSK Flashcards
Kernicterus - definition, neuro effects?
Kernicterus = uncommon complication of hyperBIL (rarely reported in dogs).
Bilirubin causes neuronal necrosis of selected brain nuclei –> acute neuro signs including seizures,
opisthotonus, abnormalities in muscle tone, decreased feeding, lethargy. If TBIL [ ] not decreased –> permanent impairments in muscle
tone, hearing & oculomotor function.
Canine degenerative myelopathy (DM) - pathogenesis & disease stages?
Late-onset progressive neurodegenerative disease affecting many pure and mixed-breed dogs. Homogenous clinical spectrum within and across breeds. 4 stages of disease progression (see table).
CSx - multisystem neurodegeneration, resulting from progressive axonal
degeneration of the central and peripheral NS. Superoxide dismutase 1 gene (SOD1) mutations (SOD1:c.118A, SOD1: c.52T) are risk factors for DM, mostly autosomal recessive inheritance. Note SOD1 mutations are incompletely penetrant, so genetic screening is insufficient for diagnosis - ideally need spinal cord histopath.
Paroxysmal dyskinesia (PD) - definition & classifications?
Green JVIM 2021
Group of movement disorders (MDs) characterized by recurring episodes of involuntary hyperkinetic movements, ballism, dystonia, athetosis, or chorea. Irregular
muscle movements typically involve the limbs, trunk, neck and/or
face, last minutes to several hours, and occur without a loss of consciousness.
3 main types:
1) Paroxysmal
kinesigenic dyskinesia (PKD) - episode is induced by an abrupt, voluntary physical movement
2) Paroxysmal non-kinesigenic dyskinesia - episodes not preceded by sudden movement or
exercise
3) Paroxysmal exertion-induced dyskinesia (PED) - episodes triggered by prolonged exercise.
Can be difficult to distinguish from focal epileptic seizures.
Define Lafora disease, its causal gene mutation and affected dog breeds.
Flegel JVIM 2021
Lafora disease is a neurological storage disease caused by an autosomal recessive genetic defect resulting in myoclonus, focal and generalized seizures.
CSx – spontaneous and myoclonic events triggered by noises or visual stimuli, hypnic myoclonus as well as generalized tonic-clonic seizures. Usually develop in dogs 6-9yo.
Defect in canine NHLRC1 (EPM2B) gene – encodes proteins laforin (carbohydrate binding phosphatase) and malin (ubiquitine ligase) –> absence of either protein results in poorly branched, hyperphosphorylated glycogen, which precipitates, aggregates and accumulates into Lafora bodies in neurons of all brain regions, reaching the highest densities in the substantia nigra, dentate nucleus and thalamic nuclei, causing neuronal malfunction –> myoclonic epilepsy. (info based on human studies)
Breeds - Wirehaired Dachshunds & Beagles (gene mutation identified). Also Basset hound, Chihuahua, French bulldog, Pointer, Miniature poodle, Welsh corgi.
Tremor ddx
Idiopathic head tremor:
a) Definition
b) Predisposed breeds
a) Idiopathic paroxysmal movement disorder. Sudden onset of short episodes with horizontal or vertical
rhythmical tremor-like movements of the head without loss of responsiveness; usually episodes can be interrupted by distractors (e.g. food). Stress can exacerbate episodes.
b) Dobers (early-onset familial + late-onset sporadic forms), Bulldogs, Boxers, Labs
Edrophonium
a) MOA
b) Indications
c) AE
d) Drugs with similar MOA
a) Short-acting anticholinesterase agent. Inhibits AChE by reversible electrostatic attachment to the enzyme, thereby blocking its hydrolytic activity on ACh –> ACh accumulates in the synaptic cleft to prolong cholinergic stimulation.
b)
- Presumptive MG (Tensilon response test). *NB for focal MG e.g. facial twitching - assess palpebral reflex after giving drug.
- Reversal of non-depolarizing neuromuscular blocking agents
c) Cholinergic signs (salivation, lacrimation, urination, defecation, GI distress, emesis aka “SLUDGE”). Have atropine 0.02 – 0.04 mg/kg IV on hand, some recommend to give it immediately before edrophonium.
*Cholinergic crisis:
- Respiratory effects (increased bronchial secretions, bronchospasm, pulmonary edema, respiratory paralysis)
- Ophthalmic effects (miosis, blurred vision, lacrimation)
- CVS effects (bradycardia or tachycardia, hypotension, cardiac arrest)
- Muscle cramps, weakness.
d)
- Pyridostigmine PO - directly competes with ACh for attachment to AchE. Vs neostigmine - 4.4x less potent, slower onset & longer DOA, fewer adverse GI effects.
- Neostigmine SQ/IV - competes with ACh for AchE binding –> forms a carbamyl-ester complex that is hydrolyzed at a slower rate than that of an Ach-AchE complex –> ACh accumulation with a resultant exaggeration & prolongation of its effects.
a) List 3 brain MRI features which can aid in identifying dogs with intracranial hypertension.
b) A direct ICP threshold of …..mmHg had 90% sens & 69% spec for predicting intracranial hypertension.
Giannasi JVIM 2020
a) MRI features - brain herniation (structural anatomical shift), mass effect (larger tumor size) & optic nerve size (larger optic nerve sheath diameter).
b) 15 mmHg
What is diffusion weighted imaging (DWI)?
Which 2 parameters were assessed on DWI to help detect microstructural spinal cord lesions in dogs with degenerative myelopathy?
What DWI changes were observed with DM dogs?
Johnson JVIM 2020
DWI = MRI method of signal contrast generation based on the differences in Brownian motion (of water molecules). Useful in identifying acute ischemic brain lesions.
Fractional anisotropy (FA) & mean diffusivity (MD).
*Decreased FA indicates disrupted fiber tracts and demyelination - more sensitive in the early detection of white matter microstructural changes.
Significant decreases in FA within SC regions with most severe lesions. FA decrease correlated with disease severity & neurological grade.
Name the patterns of clinical presentation seen with dogs with muscle cramps (MCs).
Main clinical feature of MC in dogs?
What were the main causes of MCs identified in dogs?
Gagliardo JVIM 2020
3 patterns.
1) Migrating pattern (stiffness/abduction of FL, followed by sustained HL flexion & fall in lateral recumbency)
2) Pelvic limbs pattern (HL flexion, prolonged muscle contraction, no FL involvement)
3) Single-limb pattern
Episodes triggered by prompting movement. Variably painful (58% dogs painful with 42% mild discomfort).
Hypocalcemia (79% dogs). Most commonly 2’ to primary hypoPTH > intestinal LSA & PLE.
Unknown cause in 21% dogs (all GSDs) - ddx idiopathic, paroxysmal dyskinesia
Effects of sex hormones on epileptic activity?
Oestrogen is pro-convulsant. Progesterone is anti-convulsant
2015 study found a pattern of seizure onset during heat & at end of diestrus (when P4 starts to decline to basal levels).
Excitatory or inhibitory neurotransmitters?
- Glutamate
- Glutamine
- Glycine
- GABA
Glutamate & glutamine (precursor) = excitatory
- Glutamate binds AMPA & NDMA
GABA, Glycine = inhibitory
- GABA channels are only permeable to Cl- –> hyperpolarises membrane
What are the proposed indications for immunosuppressive therapy in acquired myasthenia gravis in dogs?
Dogs with persistently increased AChR antibody titres despite time & supportive care
Dogs poorly responsive or poorly tolerant of anti-cholinesterase tx
Dogs with positive AChR Ab titres but negative edrophonium challenge tests - may respond poorly to other anticholinesterase drugs
Which antibiotics may worsen NM blockade in dogs with acquired MG?
Aminoglycosides, ampicillin, ciprofloxacin, erythromycin, imipenem
List breeds affected by primary/inherited paroxysmal dyskinesia?
ACVIM consensus
CKCS (episodic hypertonicity), Border Terriers (gluten-sensitive), Scottish Terriers (Scotty cramp), SCWTs, Chinooks, Doberman, SGP, Labs & JRTs
A hypokinetic paroxysmal dyskinesia has been described in which 2 dog breeds? Causal gene mutation?
Canine multiple system degeneration
Kerry Blue Terriers & Chinese crested dogs
SERAC1 mutation
