PNS, NMJ, myopathy dz Flashcards

Question

Comparative incidence of thymic mass in MG dogs vs caats

Answer 1

3% vs 52% in cats

Answer 2

ACh esterase inhibitors - narrow therapeutic index Neostigmine - given IV and rapid onset of action , almost 100% excreted by 24h Edrophonium - given parenterally and has onset of effects within 10 minutes Pyridostigmine - slower onset of action and can be given orally. Metabolised in liver

Answer 3

Cholinergic symptoms: Bradycardia --> sinus arrest SLUD Vomiting Paradoxical exacerbation of muscle weakness and fatiguability. Cholinergic crisis: GI upset, respiratory distress (from increased secretions and bronchospasm); miosis, altered HR, cardiospasm, sweating, cramps. Generally seen with overdose Can reverse with atropine or glycopyrrolate Cats reported to have increased susceptibility to side effects

Answer 4

Normal EMG and evoked CMAP But decremental decrease in CMAP with repetitive nerve stimulation

Answer 5

Trials with MM, cyclosporine, azathioprine have not reported success Use of corticosteroids considered risky due to their exacerbation of muscular weakness and potentially to increase risk of adverse effects should aspiration occur secondary to megaO. --> recommended to start at anti-inflammatory dose and titrate up. Cats may be more tolerant of adverse effects than dogs. Also reported to have more of a response compared to dogs. TPE reported in one dog in addition to corticosteroids and had clinical remission and is used in humans with all acquired MG forms.

Answer 6

Supportive care - avoid GA as this can worsen symptoms dramatically Prevention of aspiration and management if it occurs - ABx, O2, coupage, Start pyridostigmine then add corticosteroids at anti-inflammatory doses in dogs. Cats - start with steroids s more tolerant to AEs and more likely to have benefit. More prone to pyridostigmine AEs so need to titrate carefully.

Answer 7

Thymectomy required to achieve complete remission --> NB anaesthesia carries high risk in MG patients and can see clinically relevant post-op exacerbation

Answer 8

Spontaneous remission reported in cats without any interventions, though some require ongoing Tx 1y mortality in dogs is 40-60% regardless of type vs 15% in cats Recent JVIM study reported death in 35% of dogs. And that remission less likely in older dogs and those presenting with regurgitation or high ACh R Ab titres JVIM 2020 long term outcome in cats reported excellent outcome in all even 4 that did not receive any treatment --> in dogs that go into remission (and dont have thymoma) then prognosis is excellent long term.

Answer 9

Normalisation of AChR antibody titres, correlates well with clinical resolution of symptoms. More likely to occur in dogs with focal or generalised forms not associated with thymoma

Answer 10

Presynaptic = ACh synthesis defect (CHAT protein); Normal AChR. Reported in Old Danish Pointing Dogs Onset is 12 - 16 weeks of age, and a period of exercise is required before observation of skeletal muscle weakness and fatigability Decremental response on repetitive nerve stimulation No response to AChEi. Guanidine can result in electrophysiological improvement Response to albuterol (BAdr thought to stabilise the NMJ) Synaptic = defect in AChE (COLQ gene) Onset is 2-8 (up to 23 in cats) weeks of age. Known breed mutations in Labrador, Golden Retriever, Sphynx and Devon Rex cats. Genetic testing available Normal EMG (decremental response on RNS) , biopsy, negative Ab, Pyridostigmine makes fatagaility and muscle weakness worse. Post-synaptic = deficiency of postsynaptic nic AChR (CHRNE mutation) Reported in JRT and Heideterrier breeds, genetic testing available Normal EMG, decremental RNS, Administration of AChE-inhibitor results in electrophysiologic as well as temporary clinical improvement.

Answer 11

Genetic tests: Labrador and Gold Ret and cats with COLQ gene mutation JRT with CHRNE mutation Ultrastructural identification of ACh R deficiency Consistent clinical signs and development at young age Negative AChR-Ab testing Decremental response to RNS on electrodiagnostics with function otherwise normal on MNC and EMG. Edrophonium challenge test - improvement in post-synaptic disease, but can worsen synaptic disease or cause cholinergic crisis

Answer 12

Synaptic - worsen with AChEi but can improve with B2 adrenergic agonists --> thought to stabilise NMJ membrane and decrease dispersion of ACh R Post-synaptic - responde to pyridostigmine but generally transient benefit as drug resistance develops Most reported CMSs in dogs and cats have an unfavourable out-come and are fatal. However certain Jack Russell terriers and DevonRexes respectively affected by CHRNE- and COLQ-associated CMS cansurvive for years,

Answer 13

Inhibitors of ACh Esterase --> accumulation of ACh in synaptic cleft (organophosphates are irreversible inhibitors, carbamates are reversible) --> ongoing muscle stimulation and cholinergic effects --> tremors, weakness, CNS dysfunction, SLUD Can use atropine to antagonise ACh effects

Answer 14

Strenuous exercise or increased temperature --> hyperventilation, collapse with paretic and ataxic pelvic limbs and reduced pelvic reflexes Recover within 10-30mins but severe episodes can result in death Thought to be caused by defect in NT recycling (endocytosis process) Genetic test available Presentation at 2-24 months Reduce frequency of events with diazepam and phenobarbitone EMG, muscle bx and pyruvate levels are normal.

Answer 15

weakness, exercise intolerance, stiff stilted gait. Myotactic reflexes usually will stay intact but patellar reflexes can be lost in select myopathies Atrophy, focal or generalised is a frequent finding as well as myalgia. Voice change, dyspnoea, dysphagia, megaoesophagus may develop with muscles of the tongue, larynx, pharynx, or oesophagus.

Answer 16

CK Persistent elevation of four to five times normal values indicating ongoing muscle damage. ALT and AST may also be elevated. Lactate, pyruvate and carnitine levels may be abnormal at rest or after exercise. This may be more useful in mitochondrial and lipid storage myopathies. Infectious agents, 2M antibodies, genetic testing Electromyography might be able to confirm muscle or nerve disease. Muscle biopsy indicated in most cases

Answer 17

Immune mediated polymyositis (Boxers, Vizsla, Newfoundland, GSD) --> look for SLE MMM Extraocular myositis Dermatomyositis Infectious - Toxo, Neo, Lepto, Clostridial, FIV (Hepatozoonosis, Leishmaniasis, Borrelia)

Answer 18

result in progressive muscle degeneration, repeated cycles of regeneration and progressive weakness Dystrophin mutations most common --> cytoskeletal protein that deficiency of causes altered membrane permeability --> cycles of degeneration and regeneration X-linked inheritance, variable pentrace. Golden Rets, Tibetan Spaniel, Rotti, GSP, Cocker Spaniel. Also reported in cats May affect cardiac muscle as well Progression of signs is variable, can be severe and fatal in young pups to later onset especially in cats. May cause megaoesophagus. Sarcoglycan deficiency - autosomal disease in Devon Rex and Boston Terrier --> does not cause CK elevation --> membrane instability leads to cellular apoptosis Laminin alpha 2 deficiency

Answer 19

1 - slow twitch, long aerobic activities have more mitochondria, more Mgb for O2 storage. More prominent in anti-gravity muscles 2 - fast twitch: short fast bursts of activity Higher glycogen content,

Answer 20

HAC - alters muscle metabolism reducing protein synthesis and increasing catabolism, predominantly affecting type 2 myofibres --> weakness and pseudomyotonia with chronicity HypoTH --> type 2 myofibre atrophy with chronicity that is responsive to Tx

Answer 21

The result of a mutation in NaCl transporter in DCT --> K+ wasting through alterations in electrolyte exchange Persistent hypokalemia --> hyperpolarisation of muscle cells and elevation in CK/AST --> generalised weakness manifesting as ventroflexion, head bob Genetic test available and can supplement to Tx affected individuals Consider looking for aldosterone excess in older animals

Answer 22

Glycogen storage disease --> hypoglycaemia and glycogen accumulation in myofibres Lipid STORAGE dISEASE - LIPID DROPLETS IN MYOFIBRES Mitochondrial disorders - have concurrent neurological signs in many and elevated lactate PFK defect in English Springer spaniel results in haemolytic anaemia as well Congenital Myotonia of Min Schnauzers due to K channel defet Periodic paralysis due to hypokalaemia in cats

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PNS, NMJ, myopathy dz Flashcards

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