Workup and treatment of
SEIZURES
Topic Rounds, 8/21/12
Dharshan Neravanda, DVM, Diplomate ACVIM (Neurology)
Definition
 Excessive or hypersynchronous activity in the
cerebrum
 Focal/partial seizures involve a select group
of neurons
 Generalized seizures involve the entire
cerebrum
Neurons are Excitable Cells
 A seizure focus is a hyperexcitable area
 Inhibitory neurotransmitters
 GABA (gamma aminobutyric acid)
 Glycine
 Excitatory neurotransmitters
 Glutamate
 Aspartate
Generalized Seizure
 Tonic: sustained muscle contraction
 Loss of consciousness (usually)
 Opisthotonus and extensor rigidity
 Salivation, urination, defecation
 Breathing is affected
 Clonic: paddling, jerking, chewing
Focal Seizures (simple)
 Rhythmic contraction of facial
muscles
 Fly biting, tail chasing (sensory SZ)
 Licking or chewing at body part
 Autonomic signs (salivation,
vomit, diarrhea, abdominal pain)
Focal Seizure (complex)
 Impaired consciousness
 Bizarre behavior (limbic system)
 Aggression
 Extreme fear
Not a Seizure
 Narcolepsy/cataplexy
 Syncope
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
Causes of Seizures
V
I
T
A
M
I
N
D
Extracranial
Intracranial
• Vascular
• Infectious
inflammatory
• Anomaly
• Idiopathic
• Neoplasia
• Toxic
• Metabolic
Vascular
 Stroke- a sudden interruption of blood supply
 Hemorrhagic
 Ischemic
Infectious
 Bacterial
 Viral
 Rickettsial
 Fungal
 Protozoal
 Parasitic
Inflammatory (autoimmune)
 Small breed dogs
 Poodle, Maltese, Pug, Yorkie, Shih-Tzu, Lhasa
 1-7 years old
 Can be multifocal localization
 Seizures
 Vestibular
Inflammatory (autoimmune)
 Diagnosis based on CSF tap
 Diagnosis can be masked by steroids
 Evidence usually persists on MRI
Inflammatory (autoimmune)
 GME
 Pug dog encephalitis
 Necrotizing encephalitis of Yorkshire Terriers
Trauma
 Current trauma can cause seizures by direct
concussive damage
 Can cause hemorrhage
 Can set up a focus for seizures in the future
Toxins
 Lead
 Ethylene glycol
 Metaldehyde
Anomalous
 Consider age
 Hydrocephalus
 Lissencephaly
 Cortical dysplasia
 Cyst
 Many other oddball malformations
Metabolic
 Hypoglycemia
 1.
 2.
 3.
 4.
 5.
 6.
 7.
Metabolic
 Hypoglycemia
 1.Paraneoplastic
 1.
 2.
 3.
 4.
Metabolic
 Hypoglycemia
 1.Paraneoplastic
 1. Insulinoma
 2. Leiomyosarcoma
 3. Giant hepatoma
 4. Lymphoma
Metabolic
 Hypoglycemia
 1. Paraneoplastic
 2.
 3.
 4.
 5.
 6.
 7.
Metabolic
 Hypoglycemia
 1. Paraneoplastic
 2. Insulin overdose
 3. Young anorexic toy breed
 4. Liver failure
 5. Addisons
 6. Hunting dog
 7. Sepsis
Metabolic
 Hypoglycemia
 Hepatic encephalopathy
 Hyper/hypo- natremia
 Hyper/hypo- calcemia
 Uremia
 Increased viscosity (triglycerides, RBC)
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
Neoplasia
Primary
Metastatic
• Meningioma
• Glioma
• Lymphoma
• Histiocytic sarcoma
• Choroid plexus tumor
• Hemangiosarcoma
• Prostatic
• Mammary gland
Diagnostics
 CBC
 Chemistry panel
 Urinalysis
 Chest radiographs
 MRI
 CSF analysis
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?
Status epilepticus
 Increased autonomic discharge
 Tachycardia, hypertension, hyperglycemia
 Skeletal muscle contractions
 Hypoxia, lactic acidosis, hyperthermia
 Physiologic deterioration after 30 minutes
 Hypotension, hypoglycemia, hyperthermia,
hypoxia, myocardial damage
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
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
Intracranial
Idiopathic
Extracranial
Causes of Status Epilepticus
 10% of idiopathic epileptics will have status
epilepticus at some point in their life
Treatment of idiopathic
epilepsy
 Phenobarbital
 Bromide
 Levetiracetam
 Zonisamide
 Gabapentin
 Pregabalin
 Felbamate
--
+
Cl
Na
Ca
K
C. J. Landmark (2007). "Targets for antiepileptic drugs in the synapse." Med Sci Monit 13(1): RA1-7 49
Phenobarbital
 80% success (n=15)
 40% seizure free for at least 6 months
 40% had at least 50% decreased SZ frequency
 20% refractory
Phenobarbital
 Starting dose 2-4 mg/kg BID
 Takes 2-3 weeks to reach steady state
 Therapeutic blood levels 15- 45 mcg/ml
(n=42)
 Keep below 35 to avoid toxicity
Phenobarbital Side Effects
Transient
Predictable
Dose related
Idiosyncratic
Ataxia and
weakness
PU/PD/PP
Sedation
Cytopenias
Sedation if
loaded
Panting
Hepatotoxicity
Dyskinesia
Weight gain
Superficial
necrolytic
dermatitis
Phenobarbital Side Effects
 PU/PD, polyphagia
 Inhibit ADH release
 Suppress satiety ctr.
 Sedation/ataxia 1-2 weeks
 Occasional hyperexcitability
 Liver effects
 Enzyme induction
 Functional disturbances
 Cirrhosis and failure
 CNS depression likely
when [PB]>40 mcg/ml
 Respiratory depression
 Liver damage likely when
[PB]>35 mcg/ml
 Cytopenias
 Superficial necrolytic
dermatitis
 Dyskinesia
53
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
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 (19921996)." J Am Vet Med Assoc 213(10): 1449-53.
56
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
 Constipation
 Muscle pain and
anisocoria
 One report
 Pancreatitis
 Ataxia and sedation
 >30 times the rate if on
 Usually the dose
KBr+PB vs. PB alone
limiting side effects
 Can become stuporous
or demented
58
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
Zonisamide side effects
 Mild ataxia or paraparesis
 Transient vomiting
 Lethargy
 Apathy
 Anxiety, panting, restless (n=1)
 KCS (n=1)
 Polyarthropathy (n=1)
 Hepatic necrosis (n=1; idiosyncratic)
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)
Questions