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What is the definition of a seizure?
Unusual electrical activity in the brain resulting in abnormal movement or behavior.
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What is a convulsion?
paroxysms of involuntary muscular contractions and relaxations
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What is epilepsy?
a group of related disorders characterized by a tendency for unpredictable recurrent seizures, which vary widely in severity, appearance, cause, consequence and management
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Whar are epilepsy syndromes?
collections of different seizure types, patterns of onset and family history
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What are the seizure pathophysiologies?
- defective synaptic function triggers seizures
- neuronal membrane instability
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What defective synaptic functions trigger seizures?
- reduction of inhibition (GABA)
- enhancement of excitatory activity (glutamate, aspartate, ACh, NE, etc)
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What causes neuronal membrane instability in seizures?
- abnormality with K+ conduction
- defect in voltage sensitive ion channels
- deficiency in membrane ATPase linked to ion transport
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What is the definition of epilepsy?
- chronic disorder of recurrent seizures
- 2 or more seizures not provoked by other illnesses or circumstances
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How are epileptic seizures classified?
- Where does it start?
- What type - simple or complex?
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What are the characteristics of generalized seizures of epilepsy?
- no local onset
- bilateral symmetry (all over both lobes)
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How are partial, or focal, seizures characterized?
start in one lobe and may or may not spread to both lobes
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What is a simple seizure?
no loss of consciousness or alteration of psychic function
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What is a complex seizure?
impaired consciousness
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What is a tonic-clonic (grand mal) seizure?
- onset < 35 years
- immediate onset (loss of consciousness, falling)
- 5 phases - flexion, extension tremor, tonic/clonic, postictal: may see tonic or clonic alone or atonic: drop attack
- postictal: confused and lethargic minutes to hrs
- preceded by aura
- seizures last 2-5 min
- amnesia of seizure
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What is an absence (petit mal) seizure?
- onset 4-12 years
- rapid onset
- short duration EEG spike/wave at freq of 3Hz confirms
- Brief loss of consciousness
- Brief staring into space
- postictal: regains consciousness quickly, alert and able to resume activity
- seizures last 3-30 sec, can occur >100 times/day
- amnesia of seizure
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What is a myoclonic seizure?
- onset usually as infant/young child
- immediate onset
- brief jerking movements of the face and upper or whole body, may become tonic-clonic
- consciousness is usually preserved
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What is a simple partial seizure?
- onset at any age
- motor and sensory changes signal onset
- no loss of consciousness
- twitches
- Posticital: Todd's paralysis (weakness in body part involved)
- last +/- 90 sec
- may become generalized
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What is a complex partial seizure?
- onset in adulthood
- aura, anxiety, automatisms, psychiatric features, sharp EEG waves signal onset
- loss of consciousness
- rigid posturing of head/eyes
- automatisms
- Postictal: variable period of confusion, Todd's paralysis, aura/confusion
- last 2-5 min
- may become generalized
- amnesia of seizure
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What are the causes of new-onset seizures in adults?
- stroke
- head trauma
- alcohol
- neurodegenerative disease
- static encephalopathy
- brain tumors
- infection
- unknown
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What events can mimic a seizure?
- migraine
- psychogenic or pseudoseizures
- syncopal disturbances
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What sorts of things can cause seizures?
- Metabolic
- uremia
- hypoglycemia
- hyperglycemia
- hepatic failure
- nutritional deficiencies (B6)
- drug overdoseantibiotics (fluoroquinolones, B-lactams, carbapenems)
- psychiatric meds (antidepressants - bupropion, maprotiline; antipsychotics)
- analgesics (meperidine, tramadol)
- theophylline
- cyclosporin
- acyclovir
- lidocaine
- camphor
- w/d of CNS stimulants
- recreational drugs
- meningitis/encephalitis
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What are EEGs good for in seizures?
- DO NOT rule in or out epilepsy used alone
- can identify seizures as focal or generalized
- can identify pseudoseizures
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What types of imaging can be used to evaluate seizures?
- MRI (more useful)
- CT (quick, less expensive)
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What blood tests should be done to evaluate a seizure?
- electrolyte levels
- CBC
- liver-function tests
- renal function - renally adjust drugs
- albumin (phenytoin or valproate)
- substance abuse screen - unexplained generalized seizures
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What are the effects of epilepsy on patients?
- depression
- interpersonal relationships
- employability
- social functioning (loss of bladder or bowel)
- QOL (driving, swimming/bathing alone)
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What are some caveats to treating a first-time single seizure?
- no differences in 3-5 yr seizure-free rates whether treated at first or second seizure
- failure of first antiepileptic drug increases the likelihood of nonresponse
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What are the effects of poor control of epilepsy?
- neuronal degeneration
- new seizure forms
- increased frequency of seizures
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How should drug therapy be initiated in epilepsy?
- start with 1/4 to 1/3 of anticipated maintenance dose
- titrate to maintenance dose over 3-4 wks
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What should you do if monotherapy is ineffective?
Change to a new monotherapy drug and repeat the titration, keeping one concentration therapeutic at all times
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When should combination therapy be tried?
after 2-3 unsuccessful monotherapies have been tried
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What are the antiepileptic combinations used in refractory seizures?
- VPA and lamotrigine or levetiracetam - partial or generalized seizures
- CBZ and VPA - complex partial seizures
- vigabatrin and lamotrigine or tiagabine - partial seizures
- topiramate and lamotrigine or levetiracetam - numerous types
- VPA and ethosuxamide - generalized absence seizures
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How long should drugs be tapered when taking off of antiepileptics?
3-6 months minimum
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What antiepileptics work via GABA?
- VPA
- gabapentin
- vigabatrin
- BZD
- barbiturates (phenobarbitol)
- tiagabine
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What antiepileptics work via Na channels?
- phenytoin
- lamotrigine
- CBZ
- oxcarbazepine
- topiramate
- lacosamide
- zonisamide
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What antiepileptics work via Ca channels?
- VPA
- ethosuximide
- zonisamide
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What antiepileptics work by unknown/unique methods?
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What are the broad-spectrum antiepileptics?
- Reasonable choices in most adults, regardless of seizure type:
- VPA
- phenobarbital
- lamotrigine
- topiramate
- levetiracetam
- zonisamide
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What are the narrow-spectrum antiepileptics?
- limit to focal epilepsy with partial and secondarily generalized seizures. no good for juvenile myoclonic epilepsy and childhood absence seizures, may exacerbate these types
- CBZ
- oxcarbazepine
- phenytoin
- gabapentin
- tiagabine
- pregabalin
- vigabatrin
- rufinamide
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Which antiepileptics are effective for partial seizures?
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What is the narrowest spectrum antiepileptic and what is it good for?
ethosuximide - absence seizures
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AEDs are the 3rd most common cause of what?
acute liver failure
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Which AED increases ammonia levels?
VPA
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Which AEDs increase hepatic enzyme levels?
- VPA
- phenytoin
- phenobarbital
- CBZ
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Which AEDs cause loss of bone density?
- Phenytoin
- CBZ
- phenobarbital
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Which AEDs cause hyponatremia?
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Which AEDs should not be used in pts with renal calculi (stone formation)?
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Which AEDs are neutral or promote weight loss?
- lamotrigine
- topiramate
- felbamate
- zonisamide
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Which AEDs cause modest weight gain?
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Which AEDs cause substantial weight gain?
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Which AED causes heart block and aggrevates sick sinus syndrome?
CBZ
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Which AEDs prolong T interval?
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Which AED reduces white-cell count?
CBZ
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Which AED causes dose-related thrombocytopenia?
VPA
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Which AED causes gingival hyperplasia?
phenytoin
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Which AEDs cause severe rash?
- CBZ (asian descent 10x higher chance - check for HLA-B*1502 gene)
- phenytoin
- oxcarbazepine
- phenobarbital
- primidone (The previous 4 have significant cross-reactivity)
- lamotrigine
- ethosuximide
- zonisamide
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Which AEDs are not associated with SJ syndrome and are good alternatives?
- VPA
- gabapentin
- topiramate
- levetiracetam
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Which AED causes target lesions?
phenobarbital
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Which AEDs have adverse cognitive effects?
- CBZ
- VPA
- phenytoin
- phenobarbital
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Which AEDs cause the fewest cognitive effects?
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Which AED inhibits 2C9 and 2C19?
VPA
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Which AEDs induce P450s?
- phenytoin
- phenobarbital
- CBZ
- primidone
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Which AEDs are greater than 80-90% ppb?
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Which AEDs have the least chance of DI potential?
- gabapentin
- levitiracetam (good for HIV!!!!)
- zonisamide
- tiagabine
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Which AEDs cause decreased folic acid levels?
- phenytoin
- phenobarbital
- primidone
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What is the best reason to obtain AED serum concentrations?
use as a surrogate marker for adherence
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a person has an aura and unifocal convulsions which progress to bilateral convulsions involving the entire body. Which type of seizure is this most consistent with?
complex partial
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Why is phenobarbital not a first line AED?
high incidence of cognitive impairment
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How can you help avoid skin rashes from lamotrigine?
- avoid concommittant use of VPA
- start dose low (<25 mg/d)
- titrate slowly
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What are the first line AEDs for absence seizures?
avoid CBZ, phenytoin, gabapentin, pregabalin, vigabatrin
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What is the first line therapy for myoclonic seizures?
VPA
avoid CBZ, phenytoin, gabapentin, lamotrigine, vigabatrin
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What are the first line AEDs for tonic-clonic seizures?
- VPA
- CBZ
- oxcarbazepine
- lamotrigine
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What are the first line AEDs for partial seizures?
- CBZ
- gabapentin
- lamotrigine
- levetiracetam
- oxcarbazepine
- topiramate
- VPA
- zonisamide
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What AED is good for head trauma, neurosurgery, or post-stroke seizures?
phenytoin
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What drug in particular has a role in worsening polycystic ovary syndrome?
VPA
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Which AEDs increase the clearance of OCs?
- topiramate
- oxcarbazepine
- CYP-450 inducers
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Which AED has its clearance increased by OCs?
lamotrigine
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What contributes to decreased seizure control in pregnancy?
- increased drug clearance (esp lamotrigine)
- hormonal changes
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Which AED is the worst drug to use during pregnancy d/t increased risk of birth defects and lowering of IQ scores?
VPA
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What AEDs in particular require administration of supplemental folic acid in women of childbearing age?
- VPA
- CBZ
- phenytoin
- phenobarbital
- primidone
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What AEDs require additional vitamin K during pregnancy and at birth?
- phenytoin
- phenobarbital
- CBZ
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Which AEDs cause fetal hydantoin syndrome?
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What should be monitored in a breast feeding infant whose mother is on an AED?
sedation
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What is status epilepticus?
30 minutes in duration or 2 or more seizures without recovery of consciousness
Any seizure lasting 5 minutes should be considered impending status epilepticus
This is a medical emergency!
most episodes occur in people with no hx of epilepsy
75% are tonic clonic
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What are the high risk factors for status epilepticus?
- acute w/d of AED
- metabolic disorders
- concurrent illness/infection
- CNS lesion (anoxia, stroke, tumor trauma)
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What are the treatments for status epilepticus?
- supportive care (ABCs - airway, breathing, circulation)
- lorazepam DOC
- diazepam (rectal gel)
- midazolam (buccal)
- phenytoin DOC #1 (administer SLOWLY d/t dessicant- could lose blood vessel)fosphenytoin
- phenobarbital
- VPA (second after BZD for non-tonic clonic)
- monitor for cardiorespiratory toxicity d/t propylene glycol diluent (esp. phenytoin, diazepam and lorazepam)
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What is a simple febrile seizure?
- otherwise normal child between 6 and 60 months
- <15 min duration
- generalized
- occur once during a 24 hr period
- child has a fever
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What constitutes higher risk of developing epilepsy by the age of 25 in children who have febrile seizures?
- multiple febrile seizures
- younger than 12 mo at time of first febrile seizure
- family hx of epilepsy
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How do you treat a febrile seizure?
- antipyretics are INEFFECTIVE!!!
- continuous tx - phenobarbital, primidone, or VPA
- intermittent tx - diazepam or midazolam
potential toxicities outweigh relatively minor risk of simple febrile seizures
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What is the therapeutic range for CBZ?
4-12 mcg/mL
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What is the therapeutic range for phenobarbital?
15-45 mcg/mL
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What is the therapeutic range for VPA?
50-100 mcg/mL
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Which AEDs are eliminated via the kidney?
- pregabalin
- levetiracetam
- gabapentin
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What is induction and how long does it take to occur?
- adaptive increase in enzyme activity in responst to anothe agent, to protect cells from toxic substances by increasing detoxification activity
- slow, regulatory process
- maximal effect usually within 2 wks
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What is inhibition and how long does it take to occur?
- direct action on an enzyme which renders the enzyme inactive
- maximal effect usually 4-5 half-lives
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