Epilepsy Flashcards
What percentage of cats with seizures have suspected idiopathic epilepsy
Approx 1/3
What are possible vascular causes of epilepsy in cats?
Hypertensive encephalopathy Feline ischemic encephalopathy Thromboembolic diseases Polycythemia Coagulopathy
What inflammatory conditions are associated with epilepsy in cats?
Meningoencephalitis of unknown origin Cuterebriasis, dirofilariasis Rabies, pseudorabies Feline immunodeficiency virus‐infection Feline leukemia virus‐infection Feline infectious peritonitis Cryptococcosis, blastomycosis Toxoplasmosis
What are the main metabolic causes of seizures in ccats?
Hyperthyroidism Renal encephalopathy Thiamin deficiency Hepatic encephalopathy Hypoglycemia Hypocalcemia Electrolyte imbalance
What are the 4 stages of a seizure?
prodrome, aura, ictus, and postictal stages.
What are feline seizures typically like?
frequently complex focal seizures with or without secondary generalization. The ictal signs frequently include drooling, facial twitching, tremor, rapid running, mydriasis, hypersalivation, urination, and defecation. During focal seizure, a cat can remain in sternal recumbency or can show running or climbing activity. Seizures might be particularly violent
What are the main differential diagnoses for a seizure in cats (things that are not epilpsy)
behavioral changes, obsessive‐compulsive disorder, movement disorders, narcolepsy/cataplexy, sleep disorders, increased intracranial pressure, pain‐associated behavior, tremor syndromes, syncope, feline orofacial pain syndrome, vestibular or neuromuscular disorder, and other encephalopathies
How responsive are cats to epilepsy tx?
40% of cats with IE become seizure‐free, 40% show decreases of over 50% in frequency of seizure, and 20% are resistant to treatment
What is epilepsy?
not a single disease but a collection of conditions with a wide range of underlying aetiologies and pathologies resulting in recurrent seizures
What do you need to check in the hx?
- description, duration and frequency. V short or v long make a fit unlikely
- time of the day (normally at rest)
- postictal effects (disorientation, ataxia and polyphagia)
- behaviour between seizures
What signs are typical of a seizure?
more common at rest
prodrome - restlessness, anxiety
ictus - consciousness may be impared; autonomic signs (salivation, urination and defaecation)
postictal signs - confusion, blindness, ataxia
What is a focal seizure?
due to activation of only one part of one cerebral hemisphere;
called complex when there is alteration of awareness
What is a generalised seizure?
due to initial activation of both cerebral hemispheres simultaneously;
consciousness may be impaired and motor manifestations are bilateral
What stimulates narcolepsy?
Excitement
What is an audiogenic reflex seizure?
Fits in cats triggered by high pitched noises
Leviteracetam more useful than pheno for tx
What are the main classifications of seizures
- Reactive seizures
response from normal brain to transient disturbance in function from metabolic disorders or intoxication
reversible - Idiopathic Epilepsy
genetic (e.g. Lagotto Romagnolo)
suspected genetic (high breed prevalence)
of unknown cause - Structural Epilepsy
seizures provoked by intracranial pathology
vascular, inflammatory/infectious, traumatic,
anomalous, neoplastic, degenerative
Outline idiopathic epilepsy
presumed to be of genetic origin
channelopathies (mutations of genes that encode either voltagegated or ligand-gated ion channels) or other genetic diseases
most common in purebred dogs, between 6m-6y (3m-10y), normal in interictal period
What are the main ddx for structural epilepsy?
- Vascular (stroke)
- Infectious/inflammatory (viral, protozoal, bacterial; immune- mediated – MUOs)
- Traumatic (TBI)
- Anomalous (porencephaly, hydranencephaly, hydrocephalus, lissencephaly…)
- M
- I
- Neoplasia (primary or metastatic)
- Degenerative (storage diseases, CDS)
What are the main work ups of reactive seizures?
- hepatic
- electrolyte imbalance (Na, Ca)
- hypoglycaemia
- hypoxemia
- thiamine deficiency
- renal
- toxins and drugs
~10% of all seizures
~40% intoxications, 30% hypoglycemia in dogs
~40% present in SE
What are the indications for advanced investigations?
MRI and CSF
age at seizure onset ˂6m or ˃6y
interictal neurological abnormalities
Status or clusters
presumptive diagnosis of IE but drug‐resistance
to 1 AED titrated to highest tolerated dose
Cats?
What are the criteria for the diagnosis of idiopathic epilepsy?
- Tier I confidence level
CBC, biochem, urinalysis
age at seizure onset ˃6m and ˂ 6y
normal neurological examination
- Tier II confidence level Tier I + BA stimulation MRI CSF
- Tier III confidence level
Tier I + II +
EEG abnormalities
What are the aims for treating epilepsy?
- improve frequency and severity of seizures
- without causing significant side effects
- rarely can stop seizures altogether
- some breeds trickier (e.g. Border Collie)
- clusters hard to stop
How are border collies harder to tx for epilepsy?
Prone to clusters
Poor tolerance of phenobarb
What are the main treatment options for dogs?
Phenobarbital
Potassium bromide
Imepitoin
If refractory: Levetiracetam Zonizamide Gabapentin and Pregabalin Topiramate and Felbamate
What are the main treatment options for cats?
Phenobarbital Levetiracetam Gabapentin No diazepam - fulminant hepatotoxicity No potassium bromide - allergic pneumonitis No imepitoin?
Outline the mechanism of phenobarb and the dose
prolongs opening of the chloride channel at the GABAA receptor; effective in 60-80% of dogs with IE
auto-induction usually results in the need for increases in dose to maintain therapeutical levels
initial dose 3mg/kg BID in dog and 2mg/kg in cat; therapeutical serum concentration 15-40µg/ml (aim for 25-30µg/ml)
steady-state 10-14d, ideally measure trough levels
loading dose: 3mg/kg slow IV q30-60min for a total of up to 20mg/kg
What are the s/e of phenobarb and how do you monitor it?
sedation (worse after starting therapy or increase of dose), ataxia,
PU/PD, polyphagia
mild to moderate increases in ALP and ALT
main adverse effects (usually reversible):
1. potential for hepatotoxicity (check BAs, biochemistry)
2. blood dyscrasias (probably idiosynchratic)
• neutropaenia, anaemia, thrombocypaenia
check serum concentrations, biochemistry and haematology
2 weeks
3 months
q6 months
How does imepitoin work?
partial agonist at the benzodiazepine site of the GABA receptor, weak Ca channel blocker
anxiolytic effects – useful?
immediate effect?
10-30mg/kg BID; start 10-15mg/kg and increase if necessary
no need to do serum levels, just increase to effect but no improvement in seizure control above 30mg/kg…
Outline the s/e of imepitoin
side-effects less common and short-lived
hyperactivity, polyphagia, polyuria, polydipsia, sedation, hypersalivation, vomiting, ataxia, change in behaviour, anorexia, diarrhoea
routine bloods? – at 4 weeks and then q6m…
no data for cats
useful for clusters? Last study says not so good…
no IV formulation so cannot use in status
Outline the pharmacokinetics of KBr
filtered by glomerulus then reabsorbed by kidneys in competition with Cl-
competes with Cl- for renal elimination – ↑ Cl- intake increases bromide elimination - NO DIET CHANGES!!
20-30mg/kg SID with food, therapeutical serum concentration 1-2 mg/ml (with PB) or 1-3mg/ml alone
steady-state at 2.5-3m, measure at any time of day (1-3m)
loading dose if in a hurry (40mg/kg TID for 3-5d) – NOT EASY…
What are the s/e of KBr
sedation, ataxia, weakness, PU/PD, polyphagia
nausea, vomiting (direct gastric irritation)
- liquid form and with food
- divide into BID
- increased risk of pancreatitis
coughing and allergic pneumonitis in cats
Bromism: stupor or coma, disorientation, ataxia, paresis, blindness, dysphagia
stop bromide, in severe cases administer NaCl slowly
Outline the use of leviteracetam
initial dose 20-25mg/kg TID (possibly higher dose if on PB)
70% to 90% excreted unchanged in urine; remainder hydrolyzed in serum and other organs
IV loading dose 60mg/kg
very few side-effects, transient sedation
1. myoclonic seizures, possibly also focal
2. patients with hepatic problems (e.g. PSS)
3. cats (mild sedation and decreased appetite uncommon)
4. possibly used as pulse therapy in CS?
5. SE as IV formulation
6. potential antiepileptogenic effect
Outline the use of zonisamide
initial dose 5mg/kg BID (10mg/kg if on PB)
metabolised by liver
steady-state in 3-4 days
transient sedation, anorexia
hepatotoxicity and haematological changes (neutropaenia)
possibly useful in cats
very expensive
When should AEDs be monitored?
- steady-state after starting treatment or after loading
- if seizure frequency worsens
- if there are signs of toxicity
- q6-12m to check if changes in pharmacokinetics have affected
blood concentrations - mainly phenobarbital and potassium bromide – not just within range but at appropriate level for seizure frequency!
What is refractory epilepsy
therapeutical levels of 2 medications but less than 50% reduction in seizures ~30% of cases with epilepsy Look for: diagnostic errors: 1. non-epileptic paroxysmal event 2. symptomatic epilepsy ineffective drugs incorrect dosing, timing, diet poor owner compliance
What are the main theories behind what causes refractor epilepsy?
altered expression of drug transporters in brain, which pump AEDs away
changing drug targets in patients with recurrent seizures, making them resistant to AEDs
What should you do with refractory epilepsy?
start with most appropriate AED or if unknown the one you have the most experience with
measure levels when appropriate and increase dose if still seizures and no significant side-effects; keep repeating
add 2nd AED (aim for monotherapy if possible)
add 3rd AED if necessary; if not working, try a different 3rd AED and keep rotating
diet?
look for mistakes
What are the stages of status/ cluster fits?
1st stage - ↑ autonomic activity:
hypertension, hyperglycaemia, hyperthermia, ↑CBF
2nd stage (after ~30min):
hypotension, hypoglycaemia, ↓CBF
excessive electrical activity starts causing brain damage
What are clusters/ status?
SE – seizure lasting at least 5min or ≥2 seizures without full recovery of consciousness
CS – multiple seizures over a short period of time with recovery of consciousness between them
How do you deal with multiple seizures at home?
rectal diazepam (1-2 mg/kg) can use levetiracetam as pulse in case of cluster seizures (20mg/kg TID for 48-72h)
How do you deal with clusters/ status in hosp?
IV or rectal diazepam or midazolam up to 3x
load IV with PB or continue q12h
Diazepam (0.5-1mg/kg IV or 1-2mg/kg PR) or Midazolam (0.2mg/kg IV) repeat up to 3 times while loading with PB (3mg/kg slow IV q15m-4h up to a
total of 20mg/kg in 24h in dogs and 15mg/kg in cats; then 3mg/kg BID)
If this fails, can use levetiracetam • loading dose 60mg/kg IV (slowly) • 20mg/kg TID IV or PO • 40mg/kg rectal (solution through urinary catheter) can load on KBr • rectally if cannot swallow or orally • 30-40mg/kg TID for 3-5 days • significant sedation, ataxia, confusion for a few weeks
What are the 4 stages of status epilepticus?
early - ongoing seizure due to failure of mechanisms responsible for seizure termination
established – SE that persists after treatment with benzodiazepines
refractory – SE that fails to abort after a first line (usually a benzodiazepine) and a second-line antiseizure drug
super-refractory – SE that continues or recurs 24 h or more after onset of anaesthetic therapy
Outline the use of benzodiazepines
enhance GABA effect at GABAa receptor
not good as maintenance therapy:
1. short half-life
2. development of tolerance over a few weeks
3. cross-tolerance: won’t work in an emergency!!!
diazepam (0.5mg/kg/h) or midazolam CRI (0.3mg/kg/h), taper over 18- 24h
++ strong anti-epileptic action
– tendency for rapid and acute tolerance to develop, risks of hepatic and renal impairment, milder respiratory and cardiac depressant
Outline the use of propofol
direct activation of the c-aminobutyric receptor–chloride ionophore complex and by inhibiting NMDA glutamate receptors
may be more suited in cases with hepatic encephalopathy, established SE and some intoxications
care with possibility of Heinz body anaemia in cats -
2-8mg/kg bolus, then 4-12mg/kg/h and slowly taper over 18-24h
if using infusion – use preservative free formulation (≥ 40ml/kg)
++ very rapid onset and recovery even after prolonged infusion, responsiveness allows greater control of the level of anaesthesia no serious drug–drug interactions
– mild hypotension or cardiocirculatory depression, risk of misinterpreting common drug-induced involuntary movements as seizures
What are the aims of monitoring AED therapy?
(i) Determine effective drug concentrations after initiation of successful treatment (as appropriate);
(ii) Determine if drug failure is because of pharmacokinetic factors so as to focus on a change
in dose (metabolic tolerance) or pharmacodynamic factors so as to focus on a change of drugs (functional tolerance);
(iii) Determine if treatment failure is caused by poor compliance or an inadequate or changed drug concentration;
(iv) Prevent toxic effects; and
(v) Aid with individualization of treatment
When should phenobarb testing be done
Ideally in the am prior to eating or getting meds
How does phenobarb affect other drugs?
increase clearance of several other AEDs, including levetiracetam, zonisamide and clorazepate
When are KBr measurements recommended to be taken?
recommended at the first steady-state concentration point between 6 and 12 weeks then on an
annual basis or if > 3 seizures occur before the next
scheduled evaluation, or if signs of toxicity are suspected. Because of the long elimination half-life, samples can be collected at any time point >2 h after
dosing to avoid any peak effect variability
What are the 4 types of adverse events?
Type I: Predictable and directly related to pharmacologic effects in a dose-dependent fashion
Type II: Unpredictable (idiosyncratic) and potentially life-threatening
Type III: Cumulative with long-term treatment and
potentially life-threatening
Type IV: Delayed (carcinogenic or teratogenic) and
life-threatening
