Not a Seizure Vestibular event Head-bobbers Involuntary movement disorders
What is a Seizure? Stereotypical Involuntary Abnormal EEG during the event
Stages of a Seizure Prodrome: hours to days prior Restlessness, vocalizing Aura: seconds to minutes prior (the start of the SZ) Hide, clingy, agitated, vomit Ictus Postictus: minutes to days after Disoriented, restless, ataxic, blind, deaf
Idiopathic Age at onset: Breed: Neuro exam: Type of SZ:
Idiopathic criteria Age at onset: 1 to 6 years Breed: Purebreed (genetic) Neuro exam: Normal interictal exam Type of SZ: Generalized or Partial
Idiopathic criteria No medical history (toxin, travel, systemic health, medications) Greater than 6 months of SZ as the only clinical sign Younger dogs with severe seizures Older dogs with mild seizures
Goals of Treatment Stop seizures Decrease seizure frequency Decrease seizure severity
When to start treatment? Any episode of status epilepticus SZ > 5minutes 2 or more SZ without full recovery of consciousness between them Many seizures in a short period of time Underlying progressive disorder causing seizures
When NOT to start treatment? Single seizure Infrequent seizures Provoked seizure?
Treatment of status epilepticus Stop the seizure Systemic support After the seizure stops…
Treatment of status Stop the Seizure Diazepam 0.25 to 0.5 mg/kg IV or 1 to 2 mg/kg PR Midazolam 0.2 to 0.4 mg/kg IV or IM Can be repeated up to 3 times Higher doses are needed for dogs on Phenobarbital Propofol to effect (4 to 6mg/kg) slowly!
Treatment of status epilepticus Systemic support A-B-Cs Flow-by oxygen Treat hyperthermia down to 102 deg F
After the seizure stops… Prevent the next ones: Phenobarbital Levetiracetam Diazepam CRI
After the seizure stops… Phenobarbital is the best bet for prolonged seizure prevention 3 to 4 mg/kg doses IV Loading dose is 12-16 mg/kg in 24 hours Considered background therapy
After the seizure stops… Levetiracetam Single injection of 60mg/kg Undiluted over 5 minutes Extravasation does not cause tissue damage 56% of dogs will be seizure free for 24 hours Hardy BT, Patterson EE, Cloyd JM, Hardy RM, Leppik IE. Double-masked, placebo-controlled study of intravenous levetiracetam for the treatment of status epilepticus and acute repetitive seizures in dogs. J Vet Intern Med 2012; 26(2): 334-40.
After the seizure stops… Choose the dose that worked and set that as the hourly rate 0.5 to 2 mg/kg/hr diluted in D5W or 0.9% NaCl Run for about 6 hours then reduce rate Can use midazolam with same guidelines This is short-term prevention only
Refractory Status Epilepticus Repeat phenobarbital injections Maximum 24 mg/kg in 24 hours May get respiratory depression Propofol to effect (4 to 8 mg/kg slowly) Give through a 25 gauge needle If seizures return when awake, it’s time for anesthesia
Refractory Status Epilepticus Phenobarbital infusion 2-4 mg/kg/hr Maximum 24 mg/kg in 24 hours Propofol to effect (4 to 8 mg/kg slowly) Give through a 25 gauge needle If seizures return when awake, it’s time for anesthesia
Anesthetizing the status patient Must be intubated! Propofol CRI (6 to 12 mg/kg/hr) Isoflurane (stay at or below 1% MAC to minimize cerebral vasodilation) Taper dose q2h (to effect) Remember to continue background phenobarbital
Causes of Status Epilepticus Idiopathic Extracranial Intracranial
Causes of Status Epilepticus 10% of idiopathic epileptics will have status epilepticus at some point in their life
Phenobarbital Side Effects Transient Ataxia and weakness Sedation if loaded Predictable PU/PD/PPPantingWeight gain Dose related SedationHepatotoxicity Idiosyncratic CytopeniasDyskinesia Superficial necrolytic dermatitis
Phenobarbital Monitoring CBC and chemistry 3 months after starting Every 6 months thereafter ALP will rise, don’t freak out Keep ALT < 200 If you are confused, a bile acids challenge is the most sensitive test for liver damage
Phenobarbital Monitoring Serum levels Keep <30 to avoid sedation Keep <35 to avoid hepatotoxicity Not needed if well controlled and mild side effects Useful if difficult to control and worry about giving too much Check at least 2.5 weeks after a dose increase Do not use serum-separator tubes Sample at same # of hours after dosing each time
Bromide Efficacy as Add-on Dose of KBr: 22-40 mg/kg/d Decrease dose by 15% to use NaBr Efficacy as add-on: ~70% of dogs Therapeutic range: 1000-3000 mcg/ml About 50% can or discontinue PB Aim for [Br] > 2000 mcg/ml 56 Trepanier, L. A., A. Van Schoick, et al. (1998). "Therapeutic serum drug concentrations in epileptic dogs treated with potassium bromide alone or in combination with other anticonvulsants: 122 cases (1992- 1996)." J Am Vet Med Assoc 213(10): 1449-53.
Bromide Very long half-life (25 days) 3 weeks to get clinical effect More rapid effect with loading dose 5 months to reach steady state Loading dose is 400 to 600mg/kg Give over 5 days Will cause sedation and ataxia Cheap
Bromide Side Effects Vomiting Very salty, squirt in bread Transient sedation PU/PD/PP Ataxia and sedation Usually the dose limiting side effects Can become stuporous or demented 58 Constipation Muscle pain and anisocoria One report Pancreatitis >30 times the rate if on KBr+PB vs. PB alone
Zonisamide 80% response rate in difficult to control epileptics on phenobarbital 60 to 80% seizure reduction in responders Possible loss of response long-term Can use as a first line drug Dose: 5 to 10 mg/kg BID as first line drug 10 mg/kg BID if on phenobarbital
Levetiracetam 50% response rate in resistant epileptic dogs 70% seizure reduction in responders Most responders lose benefit after 4 to 8 months Good adjunct to phenobarbital in cats 70% response rate
Levetiracetam Don’t use as a daily anticonvulsant in dogs Use instead to prevent additional seizures in dogs known to cluster 20mg/kg TID for 3 days Give first dose after recovery from first seizure May cause sedation Can use similarly in dogs with a detectable prodromal period
Levetiracetam Can be used as a first line drug in cats 10 to 30 mg/kg TID (BID is acceptable)