Epilepsy

Question 1

A seizure is…?

An epileptic seizure is…?

A reactive seizure is…?

Answer 1

A seizure is any sudden, brief and transient
attack of illness.

Epileptic seizure is the clinical manifestation of
episodic excessive and asynchronous electrical
activity in the brain.

Reactive seizure is caused by an exctracranial
metabolic or toxic cause.

Question 2

Epilepsy is…?

Status epilepticus (status epilepticus) is…?

A cluster seizure is…?

Answer 2

Epilepsy is a condition in which two or more
epileptic seizures occur >24 hours apart.

Status epilepticus (status epilepticus) is either
* a single seizure lasting >5min
or
* two or more consecutive seizures lasting 5
min. or longer, and in the meantime the
animal does not regain consciousness.

A cluster seizure is
* two or more seizures within 24h, animal
regains consciousness in the meantime.

Status epilepticus and cluster seizures always need emergency treatment!

Question 3

Broad Classification of epilepsy.

Answer 3

Idiopathic epilepsy (IE)
or
Structural epilepsy

Question 4

Describe Idiopathic epilepsy (IE)

Answer 4

IE is a functional disease of the brain:
* confirmed genetic cause
* suspected genetic cause, due to a high
occurrence in the pedigree
* or unknown reason

NB! Condition is normal between episodes!

Question 5

Describe Structural epilepsy.

Answer 5

Structural brain-related cause:
* inflammatory
* neoplasia
* trauma
* anomalies

NB! Neurological deficits present between the
episodes!

Question 6

In case of a patient with seizures, you’re main consideration should be…

Answer 6

whether it is a reactive seizure with underlying extracranial cause?
* metabolic
* toxic

Or, is there an intracranial cause?
* functional disease (like idiopathic epilepsy)
* structural cause (inflammatory, neoplasia, trauma, anomaly)

Question 7

Prevalence of epilepsy in dogs. (6)

Answer 7

• one of the most common neurological diseases
• Idiopathic Epilepsy prevalence 0,6-0,75% of the general dog population.
• dogs aged 6 months to 6 years have a higher
  prevalence of idiopathic epilepsy.
• suspected inflammatory brain disease is more
  common in smaller breeds.
• more extra-axial tumours in large dogs.
• 11,8 % of dogs with structural epilepsy are normal completely between episodes! The odd seizure may be the only sign for a while when usually there will be CN deficits with structural issues.

Question 8

Prevalence of epilepsy in cats.

Answer 8

• less often in cats than in dogs.
• IE prevalence 22-57% of cats with recurrent seizure disorders.
• > 7 year old cats are more likely to have structural epilepsy
• 12,2% cats with structural epilepsy are normal
  between episodes (no discernible CN deficits).

Question 9

Describe focal seizures. (6)

Answer 9

• one cerebral hemisphere is involved
• consciousness normal or altered (confused, doesn’t recognize owner) - difficult to assess objectively though!
• twitching of facial muscles, rhythmic blinking of the eyes, twitching head or movement of one limb
• mydriasis, salivation, vomiting, vocalisation
• anxiety, restlessness, seeking closeness
• can become a generalized seizure

Question 10

Describe generalized epileptic seizures. (4)

Answer 10

• both cerebral hemispheres are involved
• abnormal consciousness, loss of consciousness
• movements can be tonic, clonic, tonic-clonic, atonic
• salivation, urination, defecation

Tonic seizures cause a stiffening of muscles while clonic seizures are characterized by jerking or twitching.

Question 11

Epileptic seizure phases (4)

Answer 11

prodromal phase
aura
ictus
postictal phase

Question 12

Describe epileptic seizure prodromal phase.

Answer 12

Duration from min-days.

Question 13

Describe epileptic seizure aura phase.

Answer 13

Lasts seconds before induction of ictus phase.

Question 14

Describe epileptic seizure ictus phase.

Answer 14

The actual seizing phase.

If it lasts over 5 min, its called status epilepticus.

Question 15

Describe epileptic seizure postictal phase.

Answer 15

The disoriented post phase that can even last days!

Question 16

What happens during a seizure? (4)

Answer 16

• A seizure lasting longer than 30 minutes
  causes histopathologically detectable
  lesions!
• Primary and secondary brain damage
  occurs!
• The longer the seizure lasts, the harder it
  is to control!
• Some owners become so accustomed to seizures that they “forget” the harm they can cause. Explain to the owner why seizures are really bad and need to be prevented!

Question 17

Decribe the primary brain damage that can occur during seizures. (5)

Answer 17

• locally increased metabolism
• Activation of NMDA receptors results in an
  excessive inflow of Ca-ions, may lead to
  active cell death-excitotoxicity.
• Accumulation of neurotoxic substances
  (aspartate, free radicals and their metabolites, nitrites, nitrates).
• Cell membrane and mitochondrial damage.
• Apoptosis and necrosis, cerebral oedema, may even be followed by brain herniation. (rare)

Question 18

Secondary brain damage that can occur during seizures. (6)

Answer 18

• seizures have an effect on the whole body
• in the first 30 min. the sympathetic nervous
  system is strongly activated; hypertension,
  hypoxemia, hypercapnia, hyperglycemia
  occur.
• 60-90 min. blood pressure drops, blood
  supply to the brain decreases, hyperthermia and hypoglycemia due to increased muscle activity, cardiac arrhythmias, hyperkalemia sometimes.
• All the above can lead to multiple organ failure.
• Decreased cerebral blood flow, hypoxemia,
  hypoglycemia and hyperthermia leading to
  secondary brain injury.
• Certain parts of the brain are very sensitive
  to primary and secondary brain damage (f.ex.hippocampus), changes can be shown
  by MRI.

Question 19

Conditions that may look similar to an epileptic seizure: (6)

Answer 19

• syncope
• cataplexy (sudden muscle tone loss), narcolepsy
• neuromuscular weakness
• vestibular episode
• idiopathic tremor
• paroxysmal dyskinesia (movement disorder manifesting as abnormal involuntary movements that recur episodically and last only a brief time - can be very difficult to differentiate from an epileptic seizure)

Question 20

ANAMNESIS of a seizure patient.

Answer 20

It’s a good idea to recommend the use of a seizure diary and videos to the owner in order to document frequency and nature of the episodes.

Question 21

Paroxysmal dyskinesia can be differentiated from epilepsy based on

Answer 21

presence of autonomic signs such as salivation, urination, defecation. Epilepsy has autonomic signs, paroxysmal dyskinesia does not.

Paroxysmal dyskinesia is a movement disorder manifesting as abnormal involuntary movements that recur episodically and last only a brief time - can be very difficult to differentiate from an epileptic seizure.

Question 22

VITAMIND in a seizure patient

Answer 22

Question 23

Name 4 non-infectious inflammatory causes of seizures.

Answer 23

GME - Granulomatous meningoencephalomyelitis
NME - Necrotizing meningoencephalitis
NLE - Necrotizing leukoencephalitis
MUO (immune-mediated) - Meningoencephaltis of unknown origin

All of the above tend to cause seizures in your tiny dog breeds like chihuahua, yorkie, pug, pomeranian, maltese.

Question 24

Seizure Differential diagnoses according to age (dog):
what etiology is more likely for animals under 6 months old?

Answer 24

metabolic (like liver shunt, urea cycle disorders etc.), anomaly (hydrocephalus, lysosomal storage disorders etc.)

then; inflammatory, toxic, trauma

Question 25

Seizure Differential diagnoses according to age (dog): what etiology is more likely for animals 6 months old- 6 years old?

Answer 25

idiopathic epilepdy is most likely next is inflammatory, metabolic, toxic, trauma, neoplasia

Question 26

Seizure Differential diagnoses according to age (dog): what etiology is more likely for animals over 6 years old?

Answer 26

neoplasia is most likely but also, inflammatory idiopathic (late onset) metabolic

Question 27

ADVANCED DIAGNOSTICS TESTS for seizure cases (3)

Answer 27

* MRI/(CT) * CSF * EEG ## Footnote EEG = electroencephalography

Question 28

Tx goals for a seizure patient. (4)

Answer 28

* achieve a seizure-free state or reduce the frequency and severity of seizures * reduce the possibility of life-threatening conditions (cluster seizures, status epilepticus) * improve the quality of life for the patient and the owner Find out the underlying cause of seizures! * antiepileptic drugs are used for idiopathic epilepsy. * other specific drugs are needed for reactive epilepsy, structural epilepsy. Sometimes a combination of the above drugs are used.

Question 29

Idiopathic epilepsy is the most common form of epilepsy in dogs, a lifelong chronic condition. It is most seen in what type of individuals?

Answer 29

* breed predispositions exist, also in mixed breeds though * occurs in cats as well * typical age of of onset: 6 months- 6 years * there is also late-onset IE (> 6 years) * the animal is normal between episodes * causes of reactive seizures and structural epilepsy must be ruled out in order to call it idiopathic epilepsy.

Question 30

When do you start idiopethic epilepsy treatment? The rules for starting a permanent treatment: (5)

Answer 30

* if status epilepticus, then start perm. tx * if cluster seizures, same as above * if two or more seizures within 6 months then we also start seizure tx * if severe postictal symptoms (aggression, blindness) or if the phase lasts longer than 24h * if the frequency and/or severity of the seizures increases (e.g. focal to generalized) Starting treatment earlier will ensure a better outcome! * 20-40% of dogs with IE are seizure-free with treatment * 60-80% of dogs with IE have reduced seizures with treatment * 20-30% of patients have refractory IE (drug resistant)

Question 31

Idiopathic epilepsy tx. Antiepileptic drugs act on what part of the NS?

Answer 31

They act by stimulating GABA (gamma-aminobutyric acid). * GABA is the most important inhibitory neurotransmitter in the brain. * Veterinary antiepileptic drugs modulate GABAergic neurotransmission.

Question 32

Name the 3 main antiepileptic drugs.

Answer 32

* phenobarbital * imepitoin * potassium bromide ## Footnote but also levetiracetam

Question 33

Describe Phenobarbital as an antiepileptic drug.

Answer 33

* one of the oldest veterinary antiepileptic drugs * effective, reduces seizure frequency in 60- 93% of dogs with IE, when plasma concentrations are within the therapeutic range * steady state: 2 weeks * dose: 2-3mg/kg, BID, loading ## Footnote Do NOT use phenobarbital with liver disease as its metabolized through the liver.

Question 34

Describe Phenobarbital side effects. (8+)

Answer 34

Side effects are strongest during the initial 2-3 weeks after which they level out/resolve. * sedation, restlessness * ataxia * polyphagia * polydipsia/polyuria * liver toxicity * pancreatitis * superficial necrolytic dermatitis * blood: anemia, neutropenia (Viljo!), thrombocytopenia, elevated liver enzymes ## Footnote Do NOT use phenobarbital with liver disease as its metabolized through the liver.

Question 35

Describe monitoring when using phenobarbital. (4)

Answer 35

* blood test: after 14 days of initial treatment, after 3 months, every 6 months, and if seizure free then every 12 months. * run haematology, biochemistry * plus check serum drug concentration (is it in therapeutic range?) If blood concentrations are below the therapeutic range but seizures are clinically controlled, there is no need to increase the dose! treat the animal not the blood result.

Question 36

Describe imepitoin as an antiepileptic drug.

Answer 36

* for recurrent single generalized epileptic seizures, efficacy 50-70% * efficacy has not been proven in cluster seizures or in status epilepticus * steady state reached immediately * dose: 10-30 mg/kg, BID * monotherapy or combination therapy with phenobarbital * Not available in Estonia, licensed in Finland though.

Question 37

Describe imepitoin side effects. (4)

Answer 37

* polyphagia (often permanent) * apathy, drowsiness, hyperactivity * polyuria, polydipsia * urination, vomiting, diarrhoea

Question 38

Describe monitoring when imepitoin in use for seizures. (4)

Answer 38

* no significant changes occur in the blood tests * blood test before starting treatment, and every 6 months * if seizure-free, then only control 1x per year * the drug concentration in the serum cannot be determined with this drug.

Question 39

Describe potassium bromide as an antiepileptic drug.

Answer 39

* recommended for use as a combination therapy with other antiepileptic drugs. * synergistic effect with phenobarbital, efficacy 55-80% * less effective and less tolerated as monotherapy than phenobarbital. * steady state reached in about 3 months * dose: 15mg/kg BID (comb. therapy), 20 mg/kg BID (monotherapy), loading * do not use with kidney disease! * NB diet: salt content in food may affect the serum level of the drug.

Question 40

Potassium bromide side effects. (6)

Answer 40

* sedation, irritability, hyperactivity * ataxia * polydipsia, polyuria * polyphagia * nausea, vomiting, diarrhoea * pancreatitis

Question 41

Monitoring when potasssium bromide in use. (6)

Answer 41

* blood test: pre-treatment haematology, biochemistry, electrolytes * 3 months after the start of treatment or after dose change - chceck blood drug concentration * otherwise every 6 months * if seizure-free though, then 1 x per year * consider pseudohyperchloraemia (Many laboratory analyzers can’t distinguish between chloride ions (Cl⁻) and bromide ions (Br⁻).) * consider cPLI (If a dog on KBr develops GI symptoms, a vet might run a cPLI test to rule out pancreatitis.)

Question 42

Describe levetiracetam for seizures.

Answer 42

Not licensed for use in dogs but used anyway. * 57% of dogs with drug-resistant epilepsy responded to treatment with levetiracetam, then treatment response weakened (honeymoon effect). * dose: 20 mg/kg TID * Can be used as pulse therapy for cluster seizures. * do not use with kidney disease! * suitable for liver shunt patients ## Footnote Good drug option but NOT first choice.

Question 43

Side effects of levetiracetam. (4)

Answer 43

* sedation * ataxia * loss of appetite * vomiting

Question 44

Monitoring with levetiracetam use.

Answer 44

* blood test before starting treatment, after 6 months, and then 1x per year * the concentration of the drug in blood cannot be determined with this one.

Question 45

Monotherapy drugs, and combination therapy for tx of seizure activity.

Answer 45

When a single drug isn't enough to keep the seizures under control. Monotherapy drugs: * phenobarbital * imepitoin * (potassium bromide) Combination therapy suitable drugs: * phenobarbital * potassium bromide * levetiracetam And these ones even though these aren't technically antiepileptic: * zonisamide (epilepsy & parkinson's drug) * felbamate (human anticonvulsant) * topiramate (epilepsy & migraine drug) * gabapentin * pregabalin (anxiolytic, this is Lyrica)

Question 46

If you have to Switch to combination therapy (dog) follow these guidelines. (3)

Answer 46

1. Seizures not controlled even though phenobarbital levels are within therapeutic range? * < 1 seizure in 2-3 weeks, start with KBr at a maintenance dose of 15mg/kg, measure drug concentration after 3 months * > 1 seizure in 2-3 weeks, start KBr loading dose, measure blood concentration after 1 month 2. If seizures are not controlled and KBr drug levels are not within therapeutic range, increase dose with further monitoring. 3. If the KBr level is within the therapeutic range but the seizures are not controlled, add the next antiepileptic drug.

Question 47

Is there anything more you can do if already tried to use combination of antiepileptic drugs? (4)

Answer 47

* epilepsy surgery (only in case of brain neoplasia) * electrical stimulation of the vagus nerve affects the thalamus and hippocampus area, 30% reduction in seizures after 3 months (but not available in many places) * prescription diet: medium-chain triglycerides, may reduce seizures, no harm in trying * CBD oil: no convincing results, only anecdotal tales but no harm in trying

Question 48

Cats and epilepsy treatment.

Answer 48

We don't have as many good options for cats. Mostly we use phenobarbital and levetiracetam in them, beginning to use imepitoin as well (very limited studies but is safe). Do not use potassium bromide (KBr) in cats! It causes: * cough * dyspnoe * eosinophilic bronchitis

Question 49

Cats and epilepsy treatment. Phenobarbital in cats:

Answer 49

* first choice * up to 93% respond to the treatment if the drug concentration is within the therapeutic range * dose: 1,5-2,5 mg/kg * steady state reached in 2 weeks * adverse reactions: drowsiness, ataxia, polyphagia, polydipsia, polyuria, weight gain, less commonly thrombocytopenia, neutropenia, lymphadenopathy, skin lesions * monitoring: blood test after 14 days, after 6 months, then once a year (liver enzymes generally not elevated) * do not use with liver disease!

Question 50

Cats and epilepsy treatment. Levetiracetam in cats:

Answer 50

* monotherapy or, combination therapy with phenobarbital * efficiency: 7/10 cats good treatment response * well tolerated * dose: 20mg/kg, TID * side effects: salivation, drowsiness, ataxia * do not use with kidney disease!

Question 51

What is a good treatment response?

Answer 51

The interval between seizures is prolonged (up to 3x the longest pre-seizure interval and min. 3 months) also counts as a very good tx response! ## Footnote Make sure your diagnosis is confirmed!

Question 52

Reasons for Discontinuation of antiepileptic treatment.

Answer 52

* sometimes the owner's wish if the dog has been seizure-free for a long time * life-threatening side effects of antiepileptic drugs Treatment for idiopathic epilepsy is lifelong! When treatment is stopped, there is a risk of relapse of seizures which later may not respond to treatment anymore. ## Footnote ONLY levetiracetam can be discontinued cold turkey, all the others require tapering.

Question 53

Discontinuation of phenobarbital antiepileptic treatment.

Answer 53

slow dosage reduction, one third of the dose for several weeks over a total period of 3-6 months.

Question 54

Discontinuation of potassium bromide antiepileptic treatment.

Answer 54

relatively quick tapering possible, within a few weeks, in case of intoxication taper within days.

Question 55

Discontinuation of imepitoin antiepileptic treatment.

Answer 55

relatively rapid tapering within 2-3 weeks.

Question 56

Status epilepticus and cluster seizures are both...?

Answer 56

* Life-threatening conditions! * Immediate emergency treatment and hospitalisation required! * First stabilise the patient, then take the anamnesis!

Question 57

Differential diagnoses for status epilepticus? Prognosis for status epilepticus?

Answer 57

* neoplasia * encephalitis * head trauma * metabolic diseases * toxication * idiopathic epilepsy Prognosis for status epilepticus. * mortality rate: 29-38% * recurrence rate: ca 27% * prognosis is worse in structural epilepsy and if seizures are not controlled within 6h

Question 58

First aid for status epilepticus. (6)

Answer 58

* stabilisation (IV cathether, ABC), general and neurological examination as quickly as you can. * identify/treat underlying diseases (diagnostics) * stop seizures (with antiepileptic drugs) * At the same time, do the diagnostics! * Don't forget the pet owner, the costs! * The initial anamnesis can be taken by a student or assistant.

Question 59

ABC stabilization for status epilepticus.

Answer 59

Correct hypoxia. Support through hypotonia. - fluid therapy 0,9% NaCl (!), 10 ml/kg/h Reverse hyperthermia. - Stop cooling at 38-39'C. Provide sedation/anesthesia support. ## Footnote Because diazepam precipitates in Ringer's, we use NaCl for hypotension in seizing animals!

Question 60

ACVIM, status epilepticus, dog drug guidelines.

Answer 60

A-E categories Your first choice should be IV midazolam, diazepam, propofol, ketamine or phenobarbital.

Question 61

ACVIM, status epilepticus, cat drug guidelines.

Answer 61

A-E categories There is currently no good first choice option for cats. Use IV midazolam, diazepam, levetiracetam, phenobarbital or inhalant anesthetics. Propofol and ketamine are NOT recommended in cats like they are in dogs (unless no other choices of course).

Question 62

Goal Time-line for the stabilization of status epilepticus.

Answer 62

Midazolam given in the first 5-10 min.

Question 63

Treatment of status epilepticus using diazepam.

Answer 63

Dosage higher if the dog has been on phenobarbital! REC = rectally ## Footnote Because diazepam precipitates in Ringer's, we use NaCl for hypotension in seizing animals!

Question 64

Treatment of status epilepticus using midazolam.

Answer 64

You should favor midazolam over diazepam cause its faster. ## Footnote IN = intranasal

Question 65

Why do we use NaCl for hypotension in seizing animals?

Answer 65

Because diazepam precipitates in Ringer's, we use NaCl for hypotension in seizing animals!

Question 66

Treatment of status epilepticus using phenobarbital loading dose.

Answer 66

Only use if 2 x benzodiazepines havenät worked.

Question 67

Treatment of status epilepticus using potassium bromide loading dose.

Answer 67

NOT a first line option but in case of necessity... There is no injectable option of potassium bromide. It's either oral tablets or rectal solution. NOT for cats! You might resort to this when you're maximum loaded on phenobarbital and need something else.

Question 68

Treatment of status epilepticus using levetiracetam.

Answer 68

If neither phenobarbital nor potassium bromide helped, you can try this.

Question 69

Treatment of status epilepticus using ketamine.

Answer 69

Question 70

Treatment of status epilepticus using dexmedetomidine.

Answer 70

Question 71

Treatment of status epilepticus using propofol.

Answer 71

Only when ketamine and dexmedetomidine haven't helped.

Question 72

Treatment of status epilepticus using isoflurane.

Answer 72