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Define seizures
unusual electrical activity in brain resulting in abnormal movement or behavior
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define convulsion
paroxysm of involuntary muscular contractions and relaxations
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Define Epilepsy
A group of related disorders characterized by a tendency for unpredictable recurrent seizures which vary widely in severity, appearance, cause, consequence and management (chronic)
- - Chronic disorder of recurrent seizures
- - 2 or more seizures not provoked by other illnesses or circumstances.
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Define Epilepsy Syndromes
collections of different seizure types, patterns of onset and family hx (often strongly assoc with mental retardation)
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2 types of defective synaptic function that may trigger seizures
- 1. reduction of inhibition (GABA is inhibitory)
- 2. enhancement of excitatory activity (glutamate, aspartate, acetylcholine, norepi, etc)
imbalances between these main NTs
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What issues with instability of neuronal membranes may be involved in seizure pathophys?
- abnormality with K+ conduction
- defect in voltage sensitive ion channels
- deficiency in membrane ATPase linked to ion transport
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What are the 2 main pathophysiological groups seizures are classified into and how is it decided?
Based on EEG and clinical symptoms
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Name the categories and subcategories Partial (or Focal) Seizures are broken down into.
- Simple (seizures begin locally) (no LOC)
- - with motor sx
- - with special sensory or somatosensory sx
- - with psychic sx
- - autonomic
- Complex (with impairment of consciousness)
- - simple partial onset followed by impairment of
- consciousness - w/ or w/o automatisms
- - Impaired consciousness at onset - w/ or w/o
- automatisms
- Secondarily generalized (partial onset evolving to generalized tonic-clonic seizures)
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Name the categories generalized seizures are broken down into.
- Tonic, Clonic, or Tonic-clonic (grand mal)Absence (petit mal) (no convulsions)
- Lennox-Gastaut syndrome
- Myoclonic
- Atonic (astatic, akinetic)
- Infantile spasms (West syndrome)
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Beside partial and generalized, name two other categories of epileptic seizures
- Unclassified
- Status epilepticus
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Special Epileptic syndromes
- Myoclonus and myoclonic seizures
- Reflex epilepsy
- Acquired aphasia with convulsive disorder
- Febrile and other seizures of infancy and childhood
- Hysterical seizures
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Define myoclonic jerks
Brief shock-like muscular contractions of the face, trunk, and extremities
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What is an atonic seizure?
A sudden loss of muscle tone
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What are the diagnostic laboratory tests for epilepsy?
There aren't any
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Tonic-Clonic seizure (Grand mal)
Age of onset: <35 yoa
Onset: Immediate (LOC, falling)
Description: 5 phases - Flexion, Extension, Tremor, Tonic/clonic, Postictal
Postictal: confused and lethargic (minutes to hours)
Comments: preceded by aura, seizures last 2-5 min, amnesia of seizure
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Absence seizure (Petit mal)
Age of onset: 4-12 yoa
Onset: Rapid onset, short duration
Description: Brief LOC, brief staring into space, seizures last 3-30 sec, can occur >100 x per day
Postictal: Regains consciousness quickly, alert, able to resume activity
Comments: Amnesia of seizure
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Myoclonic seizure
Age of Onset: usually infants and young children
Onset: immediate
Description: Brief jerking movements of face and upper or whole body, may become tonic-clonic
Comments: consciousness is usually preserved
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Simple Partial seizure
Age of onset: any
Onset: Motor and sensory changes autonomic
Description: no LOC, twitches
Postictal: Todd's paralysis - weakness in body part involved
Comments: Last +/- 90 sec, may become generalized
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Complex partial seizure
Age of onset: adults
Onset: Aura, anxiety, automatisms, psychiatric features, sharp EEG waves
Description: LOC, rigid posturing of head/eyes, automatisms
Postictal: Variable period of confusion, Todd's paralysis, aura/confusion
Comments: last 2-5 min, may become generalized, amnesia of seizure
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Conditions that may provoke seizures, but are not epilepsy
- uremia
- hypoglycemia
- hyperglycemia
- hepatic failure
- nutritional deficiencies
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Medications that may provoke seizures (toxicity)
- Antibiotics (esp with renal impairment)
- FQs
- B-lactams
- Carbapenems (Imipenem - less with Meropenem)
- Psych meds
- Antidepressants
- - Bupropion
- - Maprotiline
- Antipsychotics
- Other Meds
- - Analgesics (meperidine, tramadol)
- - Cyclosporin
- - Acyclovir
- - Lidocaine
- - Camphor
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What can EEG findings tell us in regard to seizures?
- Whether a seizure is focal or generalized.
- Can't rule epilepsy in or out
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Goals of Antiepileptic therapy
- Early effective control (total elimination or reduction in seizure frequency and severity)
- Minimize SEs of drugs used
- Improve QOL
- Address co-morbidities
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Which AEDs did the FDA put out an advisory for, and what is the advisory about?
Increased risk of suicidal thoughts and actions
Carbamazepine, Felbamate, Gabapentin, Lamotrigine, Levetiracetam, Oxcarbazepine, Pregabalin, Tiagabine, Topiramate, Valproate, and Zonisamide
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How much does treatment with AED reduce the risk of seizures?
30-60%
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When beginning monotherapy, what is the general rule?
Start with low doses - 1/4 to 1/3 of the anticipated maintenance dose (25-50% less in elderly)
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Over what period of time should we titrate AED?
3-4 weeks
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How many times should we attempt monotherapy with AEDs before going to the next option?
2-3 times
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What must we be sure to do when crossing over drugs?
keep the concentration of one of them therapeutic
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What is a good combo for refractory partial or generalized seizures?
Valproate and lamotrigine or levetiracetam
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What is a good combo for refractory complex partial seizures?
Carbamazepine and valproate
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What is a good combo for refractory partial seizures?
Vigabatrin and lamotrigine or tiagabine
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What is a good combo for refractory seizures of numerous types?
Topiramate and lamotrigine or levetiracetam
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What is a good combo for refractory generalized absence seizures?
Valproate and ethosuximide
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1st line for Absence seizures
- Valproic acid
- Ethosuximide
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First line for Myoclonic seizures
Valproic acid
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first line for tonic-clonic seizures
- Valproic acid
- Carbamazepine
- Oxcarbazepine
- Lamotrigine
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Avoid/may worsen Absence and/or Myoclonic seizures
- CBZ
- Phenytoin
- Gabepentin
- Vigabatrin
- Pregabalin (absence)
- Lamotrigine (myoclonic)
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1st line drug for any primary generalized seizure
VPA
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First Line drugs for Partial seizures
- CBZ
- Gabapentin
- Lamotrigine
- Levetiracetam
- Oxcarbazepine
- Topiramate
- VPA
- Zonisamide
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1st line for Childhood-onset absence seizures
Ethosuximide
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1st line for benign rolandic seizures
- CBZ
- Gabapentin
- Oxcarbazepine
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1st line for Juvenile myoclonic seizures
VPA
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1st line for adolescent-onset absence seizures
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1st line for infantile spasms (West)
- Corticotropin
- ACTH
- Vigabatrin
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1st line for Lennox-Gastaut seizures
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Avoid/may worsen Childhood-onset and Adolescent-onset absence seizures and juvenile myoclonic seizures
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Factors favoring successful withdrawal of AEDs
- a seizure-free period of 2 to 4 years
- complete seizure control within 1 year of onset
- an onset of seizures after age 2 but before age 35
- a normal neurologic examination and EEG
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When should we consider d/c of treatment with AEDs?
After a 2-year seizure-free period
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Over how long should AED therapy be tapered when discontinuation of the med is the goal?
3-6 months (reduce by 1/3 each month for 3 months, OR by 25% every 2-4 weeks)
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MOA of most AEDs
- Effects on ion channels (Na+ and Ca+2)
- Augmentation of inhibitory neurotransmission (increasing GABA)
Modulation of excitatory neurotransmission (decrease/antagonize glutamate and aspartate neurotransmission)
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Broad-spectrum AEDs
- VPA
- Phenobarbital
- Lamotrigine
- Topiramate
- Levetiracetam
- Zonisamide
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What is the narrowest spectrum AED and what type of seizures is it best for?
Ethosuximide, absence seizures
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Neurotoxic adverse effects of AEDs
- sedation
- dizziness
- blurred or double vision
- difficulty with concentration
- ataxia
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Rare but serious ideosyncratic SEs of AEDs
- hepatitis
- blood dyscrasias
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Potential long-term AE of AED treatment
give supplemental Vitamin D and Calcium
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Is hepatic dysfunction a CI of AEDs?
No, usually can be righted with dosage adjustments
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How much elevation in hepatic enzymes is ok with AEDs?
up to 2x normal - be sure to monitor
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What blood cell issue might valproate cause?
thrombocytopenia
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Which blood cells might CBZ decrease?
White blood cells (leukopenia)
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Which AEDs may lead to loss of bone density?
- Phenytoin
- Phenobarbital
- CBZ
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Major SEs of CBZ
- rashes
- bone marrow suppression
- reduced WBC count
- heart block
- aggravation of sick sinus syndrome
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Which AEDs are weight neutral or cause weight loss?
- Topiramate
- Lamotrigine
- Zonisamide
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Which AEDs cause modest weight gain (5-10 lb)?
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Which anticonvulsants cause substantial weight gain (10-50 lb)?
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Which AEDs prolong the QT interval?
(avoid in pts taking methadone or other agents that prolong the QT interval)
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Which AED causes gingival hyperplasia?
Phenytoin
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Which AEDs may cause rashes?
- CBZ
- phenytoin
- oxcarbazepine
- phenobarbital
- primidone
- Lamotrigine (titrate slowly to avoid)
- ethosuximide
- zonisamide
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Which AEDs have less likelihood of causing rashes?
- VPA
- gabapentin
- topiramate
- levetiracetam
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Which AED may cause target lesions?
phenobarbital
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Which AEDs cause the lowest degree of cognitive impairment?
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Which AED inhibits hepatic metabolism?
Valproate
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Which AEDs induce hepatic metabolism?
- Phenytoin
- Phenobarbital
- Primidone (metabolized to phenobarb)
- CBZ (metabolized to pyrimate and oxcarbazepine)
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Which AED can self induce its own metabolism?
CBZ
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Avoid inducers in patients receiving these therapies
- Antiretroviral
- Organ transplant anti-rejection
- Chemotherapy
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Which AEDs are highly plasma protein bound and what effect does this have?
VPA and phenytoin
If pt has low albumin, then there would be high level of free drug which increases the concentration
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Which AEDs have the lowest potential for drug interactions?
- Gabapentin
- Tiagabine
- Levetiracetam
- Zonisamide
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Nonpharmacologic treatments for epilepsy
- Ketogenic diet
- Herbs and botanicals
- Vagal nerve stimulation
- Surgery
- Limit alcohol
- Regular sleep
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How would we treat alcohol withdrawal seizures
benzodiazepines
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Which agent should be used for seizures d/t head trauma, neurosurgery, post-stroke?
phenytoin
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What effect does estrogen have on seizures?
Activating effect
- - inhibits GABA receptors
- - Potentiates excitatory glutaminergic activity
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What effect does progesterone have on seizures?
Protective effect
- - potentiates GABA activity
- - reduces neuronal discharge rates
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Which AEDs might increase the clearance of oral contraceptives?
- CBZ, phenobarbital, phenytoin, primidone
- topiramate
- oxcarbazepine
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Which AED's clearance is increased by oral contraceptives?
lamotrigine
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Which AEDs clearance is increased in pregnancy?
- Lamotrigine (especially)
- phenytoin
- CBZ
- phenobarbital
- Ethosuximide
- Oxarbazepine
- Clorazepate
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Which anticonvulsant has the worst incidence of increasing birth defects and lowering IQ of baby?
Valproic Acid (also phenobarb)
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Some possible ways to minimize risk of birth defects
- Monotherapy
- Lowest effective doses
- Folic Acid supplementation
- Vitamin K supplementation
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What is status epilepticus?
- a refractory seizure >30 minutes in duration
- OR
- 2 or more seizures without recovery of consciousness
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How long do most seizures last? At what point is a seizure considered impending status epilepticus?
- Normally 2 minutes or less
- If the seizure has been going on for 5 minutes
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Drug treatment of status epilepticus
Initial: BZD q 10-15 min (lorazepam DOC, diazepam (IV or rectal), midazolam (buccal))
Phenytoin or fosphenytoin
Phenobarb (3rd line)
Valproate (consider for non-tonic-clonic)
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Treatment goals for status epilepticus
- Supportive care (ABCs)
- Terminate seizure activity and prevent recurrence
- Correct possible causes
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How long are simple febrile seizures and how often do they occur?
- Less than 15 minutes
- Once in a 24-hour period
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Between what ages do febrile seizures commonly occur?
6 and 60 months
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If a child has febrile seizures, is he more likely to develop epilepsy?
Very low risk - 1%
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How do antipyretics work to prevent recurrent febrile seizures?
They don't. They may be used for comfort though.
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What continuous AED therapy may be used for febrile seizures?
Phenobarb, primidone, VPA
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What meds might be used for intermittent therapy for febrile seizures?
Diazepam or midazolam
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What type of seizures does phenytoin aggravate?
Absence
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If a patient gained weight with VPA, what would another rational treatment option be?
Ethosuximide if the pt is having absence seizures. For Tonic-clonic, could try CBZ, Oxcarbazepine, Lamotrigine.
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What is the best initial treatment for status epilepticus? What is the DOC? Which med would have the longest DOA?
- Benzodiazepines
- Lorazepam
- Lorazepam (12-24 hours d/t less redistribution)
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Treatment for simple febrile seizures?
- Can use antipyretics (for comfort only)
- Toxicity of AEDs outweighs any benefit!
- Can give intermittent oral diazepam at onset of febrile illness
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Which med is effective for preventing epilepsy later in life in children who have febrile seizures?
none of them
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Which AED is best to use in an HIV pt on antiretroviral therapy to reduce the possibility of drug interactions?
Non-inducers! (so not phenytoin, phenobarb, primidone, or CBZ)
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When a woman is on oral contraceptives, which AED would probably have the most issues to worry about?
lamotrigine
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What fraction of the maintenance dose should we begin AED treatment at?
1/4 to 1/3
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Which meds would be inappropriate choices for a pt with osteoporosis and epilepsy?
Phenytoin (because it can cause loss of bone density) (also probably CBZ and phenobarbital)
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Which AED is the most damaging to IQ of neonates?
Valproate
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If a woman with epilepsy is planning to become pregnant, what steps can we take to reduce risk to the fetus?
- Monotherapy
- Folic acid
- Vitamin K
- Lowest effective doses
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Which AEDs are broad spectrum?
- Valproate
- Phenobarbital
- Lamotrigine
- Topiramate
- Levetiracetam
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Which medication is best for absence seizures?
Ethosuximide
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