Workup and treatment of Topic Rounds, 8/21/12 Dharshan Neravanda, DVM, Diplomate ACVIM (Neurology)
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Transcript of Workup and treatment of Topic Rounds, 8/21/12 Dharshan Neravanda, DVM, Diplomate ACVIM (Neurology)
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SEIZURESWorkup and treatment of
Topic Rounds, 8/21/12Dharshan Neravanda, DVM, Diplomate ACVIM (Neurology)
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Definition
Excessive or hypersynchronous activity in the cerebrum
Focal/partial seizures involve a select group of neurons
Generalized seizures involve the entire cerebrum
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Neurons are Excitable Cells A seizure focus is a hyperexcitable
area Inhibitory neurotransmitters
GABA (gamma aminobutyric acid) Glycine
Excitatory neurotransmitters Glutamate Aspartate
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Generalized Seizure
Tonic: sustained muscle contraction Loss of consciousness (usually) Opisthotonus and extensor rigidity Salivation, urination, defecation Breathing is affected
Clonic: paddling, jerking, chewing
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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)
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Focal Seizure (complex)
Impaired consciousness Bizarre behavior (limbic system)
Aggression Extreme fear
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Not a Seizure
Narcolepsy/cataplexy Syncope
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Not a Seizure
Vestibular event Head-bobbers Involuntary
movement disorders
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What is a Seizure?
Stereotypical Involuntary Abnormal EEG during the event
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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
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Causes of Seizures
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Vascular
Stroke- a sudden interruption of blood supply Hemorrhagic Ischemic
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Infectious
Bacterial Viral Rickettsial Fungal Protozoal Parasitic
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Inflammatory (autoimmune)
Small breed dogs Poodle, Maltese, Pug, Yorkie, Shih-Tzu,
Lhasa 1-7 years old Can be multifocal localization
Seizures Vestibular
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Inflammatory (autoimmune)
Diagnosis based on CSF tap Diagnosis can be masked by steroids Evidence usually persists on MRI
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Inflammatory (autoimmune)
GME Pug dog encephalitis Necrotizing encephalitis of Yorkshire
Terriers
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Trauma
Current trauma can cause seizures by direct concussive damage
Can cause hemorrhage Can set up a focus for seizures in the
future
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Toxins
Lead Ethylene glycol Metaldehyde
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Anomalous
Consider age Hydrocephalus Lissencephaly Cortical dysplasia Cyst Many other oddball malformations
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Metabolic
Hypoglycemia 1. 2. 3. 4. 5. 6. 7.
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Metabolic
Hypoglycemia 1.Paraneoplastic
1. 2. 3. 4.
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Metabolic
Hypoglycemia 1.Paraneoplastic
1. Insulinoma 2. Leiomyosarcoma 3. Giant hepatoma 4. Lymphoma
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Metabolic
Hypoglycemia 1. Paraneoplastic 2. 3. 4. 5. 6. 7.
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Metabolic
Hypoglycemia 1. Paraneoplastic 2. Insulin overdose 3. Young anorexic toy breed 4. Liver failure 5. Addisons 6. Hunting dog 7. Sepsis
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Metabolic
Hypoglycemia Hepatic encephalopathy Hyper/hypo- natremia Hyper/hypo- calcemia Uremia Increased viscosity (triglycerides,
RBC)
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Idiopathic
Age at onset: Breed: Neuro exam: Type of SZ:
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Idiopathic criteria
Age at onset: 1 to 6 years Breed: Purebreed (genetic) Neuro exam: Normal interictal
exam Type of SZ: Generalized or Partial
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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
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Neoplasia
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Diagnostics
CBC Chemistry panel Urinalysis Chest radiographs MRI CSF analysis
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Goals of Treatment
Stop seizures Decrease seizure frequency Decrease seizure severity
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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
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When NOT to start treatment? Single seizure Infrequent seizures Provoked seizure?
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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
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Treatment of status epilepticus Stop the seizure Systemic support After the seizure stops…
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Treatment of statusStop 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!
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Treatment of status epilepticusSystemic support
A-B-Cs Flow-by oxygen Treat hyperthermia down to 102 deg F
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After the seizure stops…
Prevent the next ones: Phenobarbital Levetiracetam Diazepam CRI
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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
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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.
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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
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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
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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
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Causes of Status Epilepticus
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Causes of Status Epilepticus 10% of idiopathic epileptics will have
status epilepticus at some point in their life
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Treatment of idiopathic epilepsy Phenobarbital Bromide Levetiracetam Zonisamide Gabapentin Pregabalin Felbamate
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49C. J. Landmark (2007). "Targets for antiepileptic drugs in the synapse." Med Sci Monit 13(1): RA1-7
--
KNaCl Ca
+
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Phenobarbital
80% success (n=15) 40% seizure free for at least 6 months 40% had at least 50% decreased SZ
frequency 20% refractory
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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
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Phenobarbital Side Effects
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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 Dyskinesia53
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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
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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
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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.
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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
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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
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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
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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)
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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
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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
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Levetiracetam
Can be used as a first line drug in cats 10 to 30 mg/kg TID (BID is acceptable)
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Questions