Canine & Feline Epilepsy Flashcards
What is the main cause of seizures?
neuronal excitability
- inadequate inhibition - high GABA
- excessive excitation - high glutamate
- neuronal synchronization
- genetic factors influencing ionic gradients
What cells are responsible for maintaining the resting potential and ionic charges of neurons?
glial cells control action at Na/K ATPase and the effect of excessive discharge on other cells
What is resting membrane potential?
at equilibrium, electrical gradients counteract the concentration gradients for K+
What is the Nernst equation?
calculates the membrane potential at which specific ions will be at equilibrium on both sides of a membrane
- K+ = -80 mV
- Na+ = 62 mV
- resting potential = -70 to -90 mV = cell is a K+ battery
What causes local currents created by neurons?
ATPase is activated, causing 2 Na+ molecules to move into the cell (depolarizing it) and K+ moves out
What are EPSP and IPSP?
fluctuations in membrane potential around resting potential average
- EPSP = excitatory post-synaptic potential = depolarization
- IPSP = inhibitor post-synaptic potential = hyperpolarization
What makes up the BBB? What is its function?
capillary endothelial tight junctions and astrocytic perivascular end-feet on endothelium
limits the entry of large molecules into the brain, acting as a transcellular transport system using P-gp, coded by ABCB1 (MDR1) gene
What are 5 causes of increasing seizure activity over time?
- kindling and mirroring
- neuronal plasticity
- formation of recurrent circuits by axonal sprouting
- calcium currents
- gliosis in epileptic foci, causing the loss of K+ buffering capacity
What is the most common genetic cause of epilepsy?
polygenic mutations identified in dogs
- MDR1 gene mutation in Border Collies
What is the difference between focal and generalized seizures?
FOCAL = affect part of the brain, resulting in convulsions in one side of the body, difficult to control
GENERALIZED = affect the entire brain, resulting in entire body convulsions; typically have a focal component that is not observed
Is there a test for epilepsy?
NO
- r/o extracranial causes
- history and signalment are key
- neurologic examination
- imaging (not commonly done, $$$)
What age is most commonly affected by idiopathic epilepsy?
1-5 years old
- not absolute: juvenile and late-onset epilepsy exist
When do most dogs with idiopathic epilepsy seizure?
while at rest - morning and evenings most common
- typically are normal between episodes (may be anxious0
How do seizures change with no/inadequate therapy?
commonly increase in frequency and duration
What imaging modality is preferred for diagnosing epilepsy? Why?
MRI - provides superior soft tissue detail
- CT gives details on the bone. acute hemorrhage, and post-operative implant assessment
Is CSF collection indicated in patients with epilepsy?
no - typically unremarkable with variety depending on time from last seizure
What are the goals to treating idiopathic epilepsy?
- eliminate seizures
- minimize drug side effects
- be financially responsible - imagining is expensive and do not commonly give much other information
What are 3 causes of dogs becoming refractory to drug treatment of idiopathic epilepsy?
- problems with drug targets (channel disorders)
- problems with drug delivery to targets (drug transporters)
- problems with neuronal network changes
What is considered one of the first choice anticonvulsants for dogs? Why must it be used carefully?
Phenobarbital - pro-GABA, anti-glutamate
hepatic problems arise with serum levels >35 ug/mL
What are some side effects associated with Phenobarbital usage? What rechecks are required?
- sedation
- ataxia
- PU/PD
- polyphagia with weight gain
- bone marrow suppression
check levels in 2-3 weeks and if they are normal perform blood work and bile acids q 6 months
How is the long elimination half-life of bromide addressed? What side effects are associated?
high loading dose is given to animals currently experiencing seizure episodes —> may seem groggy
- sedation
- pelvic limb stiffness, ataxia
- vomiting
- PU/PD
- polyphagia with weight gain
How does the use of bromide commonly affect chemistry profiles? How does it compare to phenobarbital?
spuriously high chloride readings - similar size
- worthwhile to give with food to avoid GI upset
- not as effective as a sole anti-seizure drug
How does gabapentin work as an anti-seizure medication?
- moderately effective in dogs with anecdotal efficacy in cats
- TID dosing required
- weakest of the new drugs
How does felbamate work as an anti-seizure medication? What side effects are associated?
very effective in dogs - TID or BID
- hepatic signs
- blood dyscrasias
How does levetiracetam (Keppra) compare to other anti-seizure medications?
- often no side effects, extended-release form available
- no hepatic metabolism
- interacts with antidepressants, antiepileptics (carbamazepine, phenytoin), and benzodiazepines
How id levetiracetam (Keppra) most commonly used?
not effective as a sole drug and commonly has a honeymoon effect where it appears effective early on
What is considered the most effective new anti-seizure drug? How does it work?
Zonisamide
works well as a sole drug with a small probability of causing hepatic toxicity
What is pregabalin? How does it work?
next generation gabapentin
binds to alpha-2-delta subunit of neuronal voltage-gated calcium channels, resulting in decreased calcium influx and release of neurotransmitters
What are the major side effects associated with the use of topiramate?
sedation and ataxia —> not common
(several proposed mechanisms of action)
How does imepitoin (Pexion) work as an anti-seizure medication? How does it compare to other medications?
partial agonist at GABA A receptors
- comparable to phenobarbital
- no hepatic enzyme elevations
- only available in Europe
What side effects are associated with imepitoin (Pexion)?
- sedation
- PU/PD
- increased appetite
- transient hyperactivity
What are 4 non-drug options for seizure control?
- CBD
- omega-3 fatty acids
- medium chain triglycerides (MCTs)
- Chinese herbal formulas - Di Tan Tang
What is are cluster seizures? Status epilepticus?
2 or more seizures occurring in a 24 hour period
prolonged seizure activity the requires intervention to stop
What is the goal of at home therapy of cluster seizures? What 3 administrations and drugs are recommended?
decrease number of seizures/clusters to avoid emergency trips
- extra-oral drug dosages of maintenance drugs
- rectal administration of levetiracetam or diazepam
- pulsed administration of oral clorazepate (1-2 mg/lg q 6-8 hrs)
What are the 5 major ways of intervening during status epilepticus?
- intranasal midazolam - syringe and atomizer
- IV ketamine
- rectal diazepam
- IV levetiracetam
- IV barbiturates or propofol
How are parasiticides related to seizure activity? Which ones should be avoided in epileptics?
Isoxazolines decrease seizure threshold
- Credelio
- Simparica Trio
- Bravecto
- NexGard
- Revolution Plus
